TY  - JOUR
AU  - Todorović, Smilja
AU  - Smiljanić, Kosara
AU  - Ruždijić, Sabera
AU  - Mladenović, Aleksandra
AU  - Kanazir, Selma
PY  - 2018
UR  - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6037071/
UR  - https://academic.oup.com/biomedgerontology/article/73/8/1036/4837193
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3541
AB  - Dietary restriction (DR) is an important experimental paradigm for lifespan and healthspan extension, but its specific contribution regarding the type, onset, and duration are still debatable. This study was designed to examine the impact of different dietary protocols by assessing the behavioral changes during aging. We exposed male Wistar rats of various age to ad libitum (AL) or DR (60 per cent of AL daily intake) feeding regimens with different onsets. The impact of DR on locomotor activity, memory, and learning was examined in 12-, 18-, and 24-month-old treated animals and controls using open field and Y-maze tests. We have also evaluated the effects of different DR's through the quantification of animal frailty, using behavioral data to create the frailty score. Our results indicated that DR improves general animal activity and spatial memory and decreases frailty with the effect being highly dependent on DR duration and onset. Notably, life-long restriction started at young age had the most profound effect. In contrast, shorter duration and later onset of restricted diet had significantly lower or no impact on animal's behavior and frailty. This study signifies the importance of DR starting point and duration as critical determinants of DR effects on healthspan.
T2  - The Journals of Gerontology: Series A
T1  - Effects of Different Dietary Protocols on General Activity and Frailty of Male Wistar Rats During Aging
IS  - 8
VL  - 73
DO  - 10.1093/gerona/gly015
SP  - 1036
EP  - 1044
ER  - 

@article{
author = "Todorović, Smilja and Smiljanić, Kosara and Ruždijić, Sabera and Mladenović, Aleksandra and Kanazir, Selma",
year = "2018",
abstract = "Dietary restriction (DR) is an important experimental paradigm for lifespan and healthspan extension, but its specific contribution regarding the type, onset, and duration are still debatable. This study was designed to examine the impact of different dietary protocols by assessing the behavioral changes during aging. We exposed male Wistar rats of various age to ad libitum (AL) or DR (60 per cent of AL daily intake) feeding regimens with different onsets. The impact of DR on locomotor activity, memory, and learning was examined in 12-, 18-, and 24-month-old treated animals and controls using open field and Y-maze tests. We have also evaluated the effects of different DR's through the quantification of animal frailty, using behavioral data to create the frailty score. Our results indicated that DR improves general animal activity and spatial memory and decreases frailty with the effect being highly dependent on DR duration and onset. Notably, life-long restriction started at young age had the most profound effect. In contrast, shorter duration and later onset of restricted diet had significantly lower or no impact on animal's behavior and frailty. This study signifies the importance of DR starting point and duration as critical determinants of DR effects on healthspan.",
journal = "The Journals of Gerontology: Series A",
title = "Effects of Different Dietary Protocols on General Activity and Frailty of Male Wistar Rats During Aging",
number = "8",
volume = "73",
doi = "10.1093/gerona/gly015",
pages = "1036-1044"
}

Todorović, S., Smiljanić, K., Ruždijić, S., Mladenović, A.,& Kanazir, S.. (2018). Effects of Different Dietary Protocols on General Activity and Frailty of Male Wistar Rats During Aging. in The Journals of Gerontology: Series A, 73(8), 1036-1044.
https://doi.org/10.1093/gerona/gly015

Todorović S, Smiljanić K, Ruždijić S, Mladenović A, Kanazir S. Effects of Different Dietary Protocols on General Activity and Frailty of Male Wistar Rats During Aging. in The Journals of Gerontology: Series A. 2018;73(8):1036-1044.
doi:10.1093/gerona/gly015 .

Todorović, Smilja, Smiljanić, Kosara, Ruždijić, Sabera, Mladenović, Aleksandra, Kanazir, Selma, "Effects of Different Dietary Protocols on General Activity and Frailty of Male Wistar Rats During Aging" in The Journals of Gerontology: Series A, 73, no. 8 (2018):1036-1044,
https://doi.org/10.1093/gerona/gly015 . .

TY  - JOUR
AU  - Pavković, Željko
AU  - Milanović, Desanka
AU  - Ruždijić, Sabera
AU  - Kanazir, Selma
AU  - Pešić, Vesna
PY  - 2018
UR  - http://doi.wiley.com/10.1111/pan.13396
UR  - http://www.ncbi.nlm.nih.gov/pubmed/29752843
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3061
AB  - BACKGROUND The effects of anesthetic drugs on postoperative cognitive function in children are not well defined and have not been experimentally addressed. AIMS The present study aimed to examine the influence of propofol anesthesia exposure on nonaversive hippocampus-dependent learning and biochemical changes involved in memory process in the dorsal hippocampus, in peripubertal rats as the rodent model of periadolescence. METHODS The intersession spatial habituation and the novel object recognition tasks were used to assess spatial and nonspatial, nonaversive hippocampus-dependent learning. The exposure to anesthesia was performed after comparably long acquisition phases in both tasks. Behavioral testing lasted for 2 consecutive days (24-hour retention period). Changes in the expression of molecules involved in memory retrieval/reconsolidation were examined in the dorsal hippocampus by Western blot and immunohistochemistry, at the time of behavioral testing. RESULTS Exposure to propofol anesthesia resulted in inappropriate assessment of spatial novelty at the beginning of the test session and affected continuation of acquisition in the spatial habituation test. The treatment did not affect recognition of the novel object at the beginning of the test session but it attenuated overall preference to novelty, reflecting retrieval of a weak memory. The expression of phosphorylated extracellular signal-regulated kinase 2 (involved in memory retrieval) was decreased while the level of phosphorylated Ca2+ /calmodulin-dependent protein kinase IIα and early growth response protein 1 (involved in memory reconsolidation) was increased in the dorsal hippocampus. The level of Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog B (neuronal activity indicator) was increased in the dorsal dentate gyrus. Enhanced exploratory activity was still evident in the propofol anesthesia exposure (PAE) group 48 hour after the treatment in both tasks. CONCLUSION In peripubertal rats, propofol anesthesia exposure affects memory retrieval and acquisition of new learning in the spatial and nonspatial, nonaversive learning tasks 24 hour after the treatment, along with the expression of molecules that participate in memory retrieval/reconsolidation in the dorsal hippocampus. These results may have clinical implications, favoring control of basic cognitive functions in older children after the propofol exposure.
T2  - Paediatric Anaesthesia
T1  - The influence of propofol anesthesia exposure on nonaversive memory retrieval and expression of molecules involved in memory process in the dorsal hippocampus in peripubertal rats.
IS  - 6
VL  - 28
DO  - 10.1111/pan.13396
SP  - 537
EP  - 546
ER  - 

@article{
author = "Pavković, Željko and Milanović, Desanka and Ruždijić, Sabera and Kanazir, Selma and Pešić, Vesna",
year = "2018",
abstract = "BACKGROUND The effects of anesthetic drugs on postoperative cognitive function in children are not well defined and have not been experimentally addressed. AIMS The present study aimed to examine the influence of propofol anesthesia exposure on nonaversive hippocampus-dependent learning and biochemical changes involved in memory process in the dorsal hippocampus, in peripubertal rats as the rodent model of periadolescence. METHODS The intersession spatial habituation and the novel object recognition tasks were used to assess spatial and nonspatial, nonaversive hippocampus-dependent learning. The exposure to anesthesia was performed after comparably long acquisition phases in both tasks. Behavioral testing lasted for 2 consecutive days (24-hour retention period). Changes in the expression of molecules involved in memory retrieval/reconsolidation were examined in the dorsal hippocampus by Western blot and immunohistochemistry, at the time of behavioral testing. RESULTS Exposure to propofol anesthesia resulted in inappropriate assessment of spatial novelty at the beginning of the test session and affected continuation of acquisition in the spatial habituation test. The treatment did not affect recognition of the novel object at the beginning of the test session but it attenuated overall preference to novelty, reflecting retrieval of a weak memory. The expression of phosphorylated extracellular signal-regulated kinase 2 (involved in memory retrieval) was decreased while the level of phosphorylated Ca2+ /calmodulin-dependent protein kinase IIα and early growth response protein 1 (involved in memory reconsolidation) was increased in the dorsal hippocampus. The level of Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog B (neuronal activity indicator) was increased in the dorsal dentate gyrus. Enhanced exploratory activity was still evident in the propofol anesthesia exposure (PAE) group 48 hour after the treatment in both tasks. CONCLUSION In peripubertal rats, propofol anesthesia exposure affects memory retrieval and acquisition of new learning in the spatial and nonspatial, nonaversive learning tasks 24 hour after the treatment, along with the expression of molecules that participate in memory retrieval/reconsolidation in the dorsal hippocampus. These results may have clinical implications, favoring control of basic cognitive functions in older children after the propofol exposure.",
journal = "Paediatric Anaesthesia",
title = "The influence of propofol anesthesia exposure on nonaversive memory retrieval and expression of molecules involved in memory process in the dorsal hippocampus in peripubertal rats.",
number = "6",
volume = "28",
doi = "10.1111/pan.13396",
pages = "537-546"
}

Pavković, Ž., Milanović, D., Ruždijić, S., Kanazir, S.,& Pešić, V.. (2018). The influence of propofol anesthesia exposure on nonaversive memory retrieval and expression of molecules involved in memory process in the dorsal hippocampus in peripubertal rats.. in Paediatric Anaesthesia, 28(6), 537-546.
https://doi.org/10.1111/pan.13396

Pavković Ž, Milanović D, Ruždijić S, Kanazir S, Pešić V. The influence of propofol anesthesia exposure on nonaversive memory retrieval and expression of molecules involved in memory process in the dorsal hippocampus in peripubertal rats.. in Paediatric Anaesthesia. 2018;28(6):537-546.
doi:10.1111/pan.13396 .

Pavković, Željko, Milanović, Desanka, Ruždijić, Sabera, Kanazir, Selma, Pešić, Vesna, "The influence of propofol anesthesia exposure on nonaversive memory retrieval and expression of molecules involved in memory process in the dorsal hippocampus in peripubertal rats." in Paediatric Anaesthesia, 28, no. 6 (2018):537-546,
https://doi.org/10.1111/pan.13396 . .

TY  - JOUR
AU  - Milanović, Desanka
AU  - Pešić, Vesna
AU  - Lončarević-Vasiljković, Nataša
AU  - Avramović, Vladimir
AU  - Tešić, Vesna
AU  - Jevtović-Todorović, Vesna
AU  - Kanazir, Selma
AU  - Ruždijić, Sabera
PY  - 2017
UR  - http://link.springer.com/10.1007/s12640-017-9730-0
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2741
AB  - Propofol is a general anesthetic commonly used in pediatric clinical practices. Experimental findings demonstrate that anesthetics induce widespread apoptosis and cognitive decline in a developing brain. Although anesthesia-mediated neurotoxicity is the most prominent during intense period of synaptogenesis, the effects of an early anesthesia exposure on the synapses are not well understood. The aim of this study was to examine the effects of neonatal propofol anesthesia on the expression of key proteins that participate in synaptogenesis and synaptic plasticity and to evaluate long-term neurobehavioral abnormalities in the mature adult brain. Propofol-injected 7-day-old rats were maintained under 2-, 4-, and 6-h-long anesthesia and sacrificed 0, 4, 16, and 24 h after the termination of each exposure. We showed that propofol anesthesia strongly influenced spatiotemporal expression and/or proteolytic processing of crucial presynaptic (GAP-43, synaptophysin, α-synuclein), trans-synaptic (N-cadherin), and postsynaptic (drebrin, MAP-2) proteins in the cortex and thalamus. An overall decrease of synaptophysin, α-synuclein, N-cadherin, and drebrin indicated impaired function and structure of the synaptic contacts immediately after anesthesia cessation. GAP-43 and MAP-2 adult and juvenile isoforms are upregulated following anesthesia, suggesting compensatory mechanism in the maintaining of the structural integrity and stabilization of developing axons and dendritic arbors. Neonatal propofol exposure significantly altered spontaneous motor activity (increased stereotypic/repetitive movements) and changed emotional behavior (reduced anxiety-like response) in the adulthood, 6 months later. These findings suggest that propofol anesthesia is synaptotoxic in the developing brain, disturbing synaptic dynamics and producing neuroplastic changes permanently incorporated into existing networks with long-lasting functional consequences.
T2  - Neurotoxicity Research
T1  - Neonatal Propofol Anesthesia Changes Expression of Synaptic Plasticity Proteins and Increases Stereotypic and Anxyolitic Behavior in Adult Rats
VL  - 32
DO  - 10.1007/s12640-017-9730-0
SP  - 247
EP  - 263
ER  - 

@article{
author = "Milanović, Desanka and Pešić, Vesna and Lončarević-Vasiljković, Nataša and Avramović, Vladimir and Tešić, Vesna and Jevtović-Todorović, Vesna and Kanazir, Selma and Ruždijić, Sabera",
year = "2017",
abstract = "Propofol is a general anesthetic commonly used in pediatric clinical practices. Experimental findings demonstrate that anesthetics induce widespread apoptosis and cognitive decline in a developing brain. Although anesthesia-mediated neurotoxicity is the most prominent during intense period of synaptogenesis, the effects of an early anesthesia exposure on the synapses are not well understood. The aim of this study was to examine the effects of neonatal propofol anesthesia on the expression of key proteins that participate in synaptogenesis and synaptic plasticity and to evaluate long-term neurobehavioral abnormalities in the mature adult brain. Propofol-injected 7-day-old rats were maintained under 2-, 4-, and 6-h-long anesthesia and sacrificed 0, 4, 16, and 24 h after the termination of each exposure. We showed that propofol anesthesia strongly influenced spatiotemporal expression and/or proteolytic processing of crucial presynaptic (GAP-43, synaptophysin, α-synuclein), trans-synaptic (N-cadherin), and postsynaptic (drebrin, MAP-2) proteins in the cortex and thalamus. An overall decrease of synaptophysin, α-synuclein, N-cadherin, and drebrin indicated impaired function and structure of the synaptic contacts immediately after anesthesia cessation. GAP-43 and MAP-2 adult and juvenile isoforms are upregulated following anesthesia, suggesting compensatory mechanism in the maintaining of the structural integrity and stabilization of developing axons and dendritic arbors. Neonatal propofol exposure significantly altered spontaneous motor activity (increased stereotypic/repetitive movements) and changed emotional behavior (reduced anxiety-like response) in the adulthood, 6 months later. These findings suggest that propofol anesthesia is synaptotoxic in the developing brain, disturbing synaptic dynamics and producing neuroplastic changes permanently incorporated into existing networks with long-lasting functional consequences.",
journal = "Neurotoxicity Research",
title = "Neonatal Propofol Anesthesia Changes Expression of Synaptic Plasticity Proteins and Increases Stereotypic and Anxyolitic Behavior in Adult Rats",
volume = "32",
doi = "10.1007/s12640-017-9730-0",
pages = "247-263"
}

Milanović, D., Pešić, V., Lončarević-Vasiljković, N., Avramović, V., Tešić, V., Jevtović-Todorović, V., Kanazir, S.,& Ruždijić, S.. (2017). Neonatal Propofol Anesthesia Changes Expression of Synaptic Plasticity Proteins and Increases Stereotypic and Anxyolitic Behavior in Adult Rats. in Neurotoxicity Research, 32, 247-263.
https://doi.org/10.1007/s12640-017-9730-0

Milanović D, Pešić V, Lončarević-Vasiljković N, Avramović V, Tešić V, Jevtović-Todorović V, Kanazir S, Ruždijić S. Neonatal Propofol Anesthesia Changes Expression of Synaptic Plasticity Proteins and Increases Stereotypic and Anxyolitic Behavior in Adult Rats. in Neurotoxicity Research. 2017;32:247-263.
doi:10.1007/s12640-017-9730-0 .

Milanović, Desanka, Pešić, Vesna, Lončarević-Vasiljković, Nataša, Avramović, Vladimir, Tešić, Vesna, Jevtović-Todorović, Vesna, Kanazir, Selma, Ruždijić, Sabera, "Neonatal Propofol Anesthesia Changes Expression of Synaptic Plasticity Proteins and Increases Stereotypic and Anxyolitic Behavior in Adult Rats" in Neurotoxicity Research, 32 (2017):247-263,
https://doi.org/10.1007/s12640-017-9730-0 . .

TY  - JOUR
AU  - Tešić, Vesna
AU  - Perović, Milka
AU  - Zaletel, Ivan
AU  - Jovanović, Mirna
AU  - Puškaš, Nela
AU  - Ruždijić, Sabera
AU  - Kanazir, Selma
PY  - 2017
UR  - http://linkinghub.elsevier.com/retrieve/pii/S0531556517302462
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2839
AB  - The administration of dexamethasone, a synthetic glucocorticoid receptor agonist, has been reported to modulate cognitive performance in both animals and humans. In the present study, we demonstrate the effects of a single high dose of dexamethasone on the expression and distribution of synaptic plasticity-related proteins, growth-associated protein-43 (GAP-43) and synaptophysin, in the hippocampus of 6-, 12-, 18- and 24-month-old rats. Acute dexamethasone treatment significantly altered the expression of GAP-43 at the posttranslational level by modulating the levels of phosphorylated GAP-43 and proteolytic GAP-43-3 fragment. The effect was the most pronounced in the hippocampi of the aged animals. The total GAP-43 protein was increased only in 24-month-old dexamethasone-treated animals, and was concomitant with a decrease in calpain-mediated proteolysis. Moreover, by introducing the gray level co-occurrence matrix method, a form of texture analysis, we were able to reveal the subtle differences in the expression pattern of both GAP-43 and synaptophysin in the hippocampal subfields that were not detected by Western blot analysis alone. Therefore, the current study demonstrates, through a novel combined approach, that dexamethasone treatment significantly affects both GAP-43 and synaptophysin protein expression in the hippocampus of aged rats.
T2  - Experimental Gerontology
T1  - A single high dose of dexamethasone increases GAP-43 and synaptophysin in the hippocampus of aged rats
VL  - 98
DO  - 10.1016/j.exger.2017.08.010
SP  - 62
EP  - 69
ER  - 

@article{
author = "Tešić, Vesna and Perović, Milka and Zaletel, Ivan and Jovanović, Mirna and Puškaš, Nela and Ruždijić, Sabera and Kanazir, Selma",
year = "2017",
abstract = "The administration of dexamethasone, a synthetic glucocorticoid receptor agonist, has been reported to modulate cognitive performance in both animals and humans. In the present study, we demonstrate the effects of a single high dose of dexamethasone on the expression and distribution of synaptic plasticity-related proteins, growth-associated protein-43 (GAP-43) and synaptophysin, in the hippocampus of 6-, 12-, 18- and 24-month-old rats. Acute dexamethasone treatment significantly altered the expression of GAP-43 at the posttranslational level by modulating the levels of phosphorylated GAP-43 and proteolytic GAP-43-3 fragment. The effect was the most pronounced in the hippocampi of the aged animals. The total GAP-43 protein was increased only in 24-month-old dexamethasone-treated animals, and was concomitant with a decrease in calpain-mediated proteolysis. Moreover, by introducing the gray level co-occurrence matrix method, a form of texture analysis, we were able to reveal the subtle differences in the expression pattern of both GAP-43 and synaptophysin in the hippocampal subfields that were not detected by Western blot analysis alone. Therefore, the current study demonstrates, through a novel combined approach, that dexamethasone treatment significantly affects both GAP-43 and synaptophysin protein expression in the hippocampus of aged rats.",
journal = "Experimental Gerontology",
title = "A single high dose of dexamethasone increases GAP-43 and synaptophysin in the hippocampus of aged rats",
volume = "98",
doi = "10.1016/j.exger.2017.08.010",
pages = "62-69"
}

Tešić, V., Perović, M., Zaletel, I., Jovanović, M., Puškaš, N., Ruždijić, S.,& Kanazir, S.. (2017). A single high dose of dexamethasone increases GAP-43 and synaptophysin in the hippocampus of aged rats. in Experimental Gerontology, 98, 62-69.
https://doi.org/10.1016/j.exger.2017.08.010

Tešić V, Perović M, Zaletel I, Jovanović M, Puškaš N, Ruždijić S, Kanazir S. A single high dose of dexamethasone increases GAP-43 and synaptophysin in the hippocampus of aged rats. in Experimental Gerontology. 2017;98:62-69.
doi:10.1016/j.exger.2017.08.010 .

Tešić, Vesna, Perović, Milka, Zaletel, Ivan, Jovanović, Mirna, Puškaš, Nela, Ruždijić, Sabera, Kanazir, Selma, "A single high dose of dexamethasone increases GAP-43 and synaptophysin in the hippocampus of aged rats" in Experimental Gerontology, 98 (2017):62-69,
https://doi.org/10.1016/j.exger.2017.08.010 . .

TY  - JOUR
AU  - Pavković, Željko
AU  - Smiljanić, Kosara
AU  - Kanazir, Selma
AU  - Milanović, Desanka
AU  - Pešić, Vesna
AU  - Ruždijić, Sabera
PY  - 2017
UR  - http://doi.wiley.com/10.1111/pan.13182
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2831
AB  - Background: Propofol is commonly used in modern anesthesiology. Some findings suggest that it is highly addictive. Aim: In this study it was examined whether propofol anesthesia exposure was able to induce behavioral alterations and brain molecular changes already described in addictive drug usage in peripubertal rats, during the onset of mid/periadolescence as a developmental period with increasing vulnerability to drug addiction. Methods: The expression of D1 dopamine receptor, a dopamine, and cAMP-regulated phosphoprotein with a Mr 32 000; Ca 2+ /calmodulin-dependent protein kinase IIα; and Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog-B was examined in peripubertal rats 4, 24, and 48 hour after propofol anesthesia exposure by Western blot and immunohistochemistry. Brain regions of interest were the medial prefrontal cortex, the striatum, and the thalamus. Anxiety and behavioral cross-sensitization to d-amphetamine were examined as well. Results: Significant increase in the expression of dopamine and cAMP-regulated phosphoprotein with a Mr 32 000 phosphorylated at threonine 34, a postsynaptic marker of dopaminergic neurotransmission, and Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog-B, a marker of neuronal activity, was detected in the thalamus of experimental animals 4-24 hour after the treatment, with the accent on the paraventricular thalamic nucleus. Significant increase in the expression of Ca 2+ /calmodulin-dependent protein kinase IIα phosphorylated at threonine 286, a sensor of synaptic activity, was observed in the prefrontal cortex and the striatum 24 hour after propofol anesthesia exposure. It was accompanied by a significant decrease in Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog-B expression in the striatum. Decreased behavioral inhibition in aversive environment and increased motor response to d-amphetamine in a context-independent manner were observed as well. Conclusion: In peripubertal rats, propofol anesthesia exposure induces transient molecular and behavioral response that share similarities with those reported previously for addictive drugs. In the absence of additional pharmacological manipulation, all detected effects receded within 48 hour after the treatment.
T2  - Pediatric Anesthesia
T1  - Brain molecular changes and behavioral alterations induced by propofol anesthesia exposure in peripubertal rats
IS  - 9
VL  - 27
DO  - 10.1111/pan.13182
SP  - 962
EP  - 972
ER  - 

@article{
author = "Pavković, Željko and Smiljanić, Kosara and Kanazir, Selma and Milanović, Desanka and Pešić, Vesna and Ruždijić, Sabera",
year = "2017",
abstract = "Background: Propofol is commonly used in modern anesthesiology. Some findings suggest that it is highly addictive. Aim: In this study it was examined whether propofol anesthesia exposure was able to induce behavioral alterations and brain molecular changes already described in addictive drug usage in peripubertal rats, during the onset of mid/periadolescence as a developmental period with increasing vulnerability to drug addiction. Methods: The expression of D1 dopamine receptor, a dopamine, and cAMP-regulated phosphoprotein with a Mr 32 000; Ca 2+ /calmodulin-dependent protein kinase IIα; and Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog-B was examined in peripubertal rats 4, 24, and 48 hour after propofol anesthesia exposure by Western blot and immunohistochemistry. Brain regions of interest were the medial prefrontal cortex, the striatum, and the thalamus. Anxiety and behavioral cross-sensitization to d-amphetamine were examined as well. Results: Significant increase in the expression of dopamine and cAMP-regulated phosphoprotein with a Mr 32 000 phosphorylated at threonine 34, a postsynaptic marker of dopaminergic neurotransmission, and Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog-B, a marker of neuronal activity, was detected in the thalamus of experimental animals 4-24 hour after the treatment, with the accent on the paraventricular thalamic nucleus. Significant increase in the expression of Ca 2+ /calmodulin-dependent protein kinase IIα phosphorylated at threonine 286, a sensor of synaptic activity, was observed in the prefrontal cortex and the striatum 24 hour after propofol anesthesia exposure. It was accompanied by a significant decrease in Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog-B expression in the striatum. Decreased behavioral inhibition in aversive environment and increased motor response to d-amphetamine in a context-independent manner were observed as well. Conclusion: In peripubertal rats, propofol anesthesia exposure induces transient molecular and behavioral response that share similarities with those reported previously for addictive drugs. In the absence of additional pharmacological manipulation, all detected effects receded within 48 hour after the treatment.",
journal = "Pediatric Anesthesia",
title = "Brain molecular changes and behavioral alterations induced by propofol anesthesia exposure in peripubertal rats",
number = "9",
volume = "27",
doi = "10.1111/pan.13182",
pages = "962-972"
}

Pavković, Ž., Smiljanić, K., Kanazir, S., Milanović, D., Pešić, V.,& Ruždijić, S.. (2017). Brain molecular changes and behavioral alterations induced by propofol anesthesia exposure in peripubertal rats. in Pediatric Anesthesia, 27(9), 962-972.
https://doi.org/10.1111/pan.13182

Pavković Ž, Smiljanić K, Kanazir S, Milanović D, Pešić V, Ruždijić S. Brain molecular changes and behavioral alterations induced by propofol anesthesia exposure in peripubertal rats. in Pediatric Anesthesia. 2017;27(9):962-972.
doi:10.1111/pan.13182 .

Pavković, Željko, Smiljanić, Kosara, Kanazir, Selma, Milanović, Desanka, Pešić, Vesna, Ruždijić, Sabera, "Brain molecular changes and behavioral alterations induced by propofol anesthesia exposure in peripubertal rats" in Pediatric Anesthesia, 27, no. 9 (2017):962-972,
https://doi.org/10.1111/pan.13182 . .

TY  - JOUR
AU  - Milanović, Desanka
AU  - Pešić, Vesna
AU  - Lončarević-Vasiljković, Nataša
AU  - Pavković, Željko
AU  - Popić, Jelena
AU  - Kanazir, Selma
AU  - Jevtović-Todorović, Vesna
AU  - Ruždijić, Sabera
PY  - 2016
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5457
AB  - A number of experimental studies have reported that exposure to common, clinically used anesthetics induce extensive neuroapoptosis and cognitive impairment when applied to young rodents, up to 2 weeks old, in phase of rapid synaptogenesis. Propofol is the most used general anesthetic in clinical practice whose mechanisms of neurotoxicity on the developing brain remains to be examined in depth. This study investigated effects of different exposures to propofol anesthesia on Fas receptor and Fas ligand expressions, which mediate proapoptotic and proinflammation signaling in the brain. Propofol (20 mg/kg) was administered to 7-day-old rats in multiple doses sufficient to maintain 2-, 4- and 6-h duration of anesthesia. Animals were sacrificed at 0, 4, 16 and 24 h after termination of anesthesia. It was found that propofol anesthesia induced Fas/FasL and downstream caspase-8 expression more prominently in the thalamus than in the cortex. Opposite, Bcl-2 and caspase-9, markers of intrinsic pathway activation, were shown to be more influenced by propofol treatment in the cortex. Further, we have established upregulation of caspase-1 and IL-1β cytokine transcription as well as subsequent activation of microglia that is potentially associated with brain inflammation. Behavioral analyses revealed that P35 and P60 animals, neonatally exposed to propofol, had significantly higher motor activity during three consecutive days of testing in the open field, though formation of the intersession habituation was not prevented. This data, together with our previous results, contributes to elucidation of complex mechanisms of propofol toxicity in developing brain.
PB  - New York: Springer
T2  - Neurotoxicity Research
T1  - The Fas Ligand/Fas Death Receptor Pathways Contribute to Propofol-Induced Apoptosis and Neuroinflammation in the Brain of Neonatal Rats
IS  - 3
VL  - 30
DO  - 10.1007/s12640-016-9629-1
SP  - 434
EP  - 452
ER  - 

@article{
author = "Milanović, Desanka and Pešić, Vesna and Lončarević-Vasiljković, Nataša and Pavković, Željko and Popić, Jelena and Kanazir, Selma and Jevtović-Todorović, Vesna and Ruždijić, Sabera",
year = "2016",
abstract = "A number of experimental studies have reported that exposure to common, clinically used anesthetics induce extensive neuroapoptosis and cognitive impairment when applied to young rodents, up to 2 weeks old, in phase of rapid synaptogenesis. Propofol is the most used general anesthetic in clinical practice whose mechanisms of neurotoxicity on the developing brain remains to be examined in depth. This study investigated effects of different exposures to propofol anesthesia on Fas receptor and Fas ligand expressions, which mediate proapoptotic and proinflammation signaling in the brain. Propofol (20 mg/kg) was administered to 7-day-old rats in multiple doses sufficient to maintain 2-, 4- and 6-h duration of anesthesia. Animals were sacrificed at 0, 4, 16 and 24 h after termination of anesthesia. It was found that propofol anesthesia induced Fas/FasL and downstream caspase-8 expression more prominently in the thalamus than in the cortex. Opposite, Bcl-2 and caspase-9, markers of intrinsic pathway activation, were shown to be more influenced by propofol treatment in the cortex. Further, we have established upregulation of caspase-1 and IL-1β cytokine transcription as well as subsequent activation of microglia that is potentially associated with brain inflammation. Behavioral analyses revealed that P35 and P60 animals, neonatally exposed to propofol, had significantly higher motor activity during three consecutive days of testing in the open field, though formation of the intersession habituation was not prevented. This data, together with our previous results, contributes to elucidation of complex mechanisms of propofol toxicity in developing brain.",
publisher = "New York: Springer",
journal = "Neurotoxicity Research",
title = "The Fas Ligand/Fas Death Receptor Pathways Contribute to Propofol-Induced Apoptosis and Neuroinflammation in the Brain of Neonatal Rats",
number = "3",
volume = "30",
doi = "10.1007/s12640-016-9629-1",
pages = "434-452"
}

Milanović, D., Pešić, V., Lončarević-Vasiljković, N., Pavković, Ž., Popić, J., Kanazir, S., Jevtović-Todorović, V.,& Ruždijić, S.. (2016). The Fas Ligand/Fas Death Receptor Pathways Contribute to Propofol-Induced Apoptosis and Neuroinflammation in the Brain of Neonatal Rats. in Neurotoxicity Research
New York: Springer., 30(3), 434-452.
https://doi.org/10.1007/s12640-016-9629-1

Milanović D, Pešić V, Lončarević-Vasiljković N, Pavković Ž, Popić J, Kanazir S, Jevtović-Todorović V, Ruždijić S. The Fas Ligand/Fas Death Receptor Pathways Contribute to Propofol-Induced Apoptosis and Neuroinflammation in the Brain of Neonatal Rats. in Neurotoxicity Research. 2016;30(3):434-452.
doi:10.1007/s12640-016-9629-1 .

Milanović, Desanka, Pešić, Vesna, Lončarević-Vasiljković, Nataša, Pavković, Željko, Popić, Jelena, Kanazir, Selma, Jevtović-Todorović, Vesna, Ruždijić, Sabera, "The Fas Ligand/Fas Death Receptor Pathways Contribute to Propofol-Induced Apoptosis and Neuroinflammation in the Brain of Neonatal Rats" in Neurotoxicity Research, 30, no. 3 (2016):434-452,
https://doi.org/10.1007/s12640-016-9629-1 . .

TY  - JOUR
AU  - Savić, Danijela
AU  - Stanković, Tijana
AU  - Lavrnja, Irena
AU  - Podolski-Renić, Ana
AU  - Banković, Jasna
AU  - Peković, Sanja
AU  - Stojiljković, Mirjana
AU  - Rakić, Ljubisav
AU  - Ruždijić, Sabera
AU  - Pešić, Milica
PY  - 2015
UR  - http://www.degruyter.com/view/j/motth.2015.1.issue-1/motth-2015-0002/motth-2015-0002.xml
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2633
AB  - Purine nucleoside analogs have been in clinical use for almost 50 years. At the beginning developed as antiviral agents, later their efficacy was demonstrated in cancer treatment, especially hematological malignances. The approval of new purine nucleoside analogs by US Food and Drug Administration (FDA) over the past decade implies that the interest for these drugs still exists. Here, we review new nucleoside analogs that are currently in preclinical or clinical development as anticancer agents. In addition, we highlight the potential for implementation of these drugs in other pathological conditions, particularly in neuroinflammation.
T2  - Molecular inhibitors in targeted therapy
T1  - Purine nucleoside analogs in the therapy of cancer and neuroinflammation
IS  - 1
VL  - 1
DO  - 10.1515/motth-2015-0002
SP  - 3
EP  - 14
ER  - 

@article{
author = "Savić, Danijela and Stanković, Tijana and Lavrnja, Irena and Podolski-Renić, Ana and Banković, Jasna and Peković, Sanja and Stojiljković, Mirjana and Rakić, Ljubisav and Ruždijić, Sabera and Pešić, Milica",
year = "2015",
abstract = "Purine nucleoside analogs have been in clinical use for almost 50 years. At the beginning developed as antiviral agents, later their efficacy was demonstrated in cancer treatment, especially hematological malignances. The approval of new purine nucleoside analogs by US Food and Drug Administration (FDA) over the past decade implies that the interest for these drugs still exists. Here, we review new nucleoside analogs that are currently in preclinical or clinical development as anticancer agents. In addition, we highlight the potential for implementation of these drugs in other pathological conditions, particularly in neuroinflammation.",
journal = "Molecular inhibitors in targeted therapy",
title = "Purine nucleoside analogs in the therapy of cancer and neuroinflammation",
number = "1",
volume = "1",
doi = "10.1515/motth-2015-0002",
pages = "3-14"
}

Savić, D., Stanković, T., Lavrnja, I., Podolski-Renić, A., Banković, J., Peković, S., Stojiljković, M., Rakić, L., Ruždijić, S.,& Pešić, M.. (2015). Purine nucleoside analogs in the therapy of cancer and neuroinflammation. in Molecular inhibitors in targeted therapy, 1(1), 3-14.
https://doi.org/10.1515/motth-2015-0002

Savić D, Stanković T, Lavrnja I, Podolski-Renić A, Banković J, Peković S, Stojiljković M, Rakić L, Ruždijić S, Pešić M. Purine nucleoside analogs in the therapy of cancer and neuroinflammation. in Molecular inhibitors in targeted therapy. 2015;1(1):3-14.
doi:10.1515/motth-2015-0002 .

Savić, Danijela, Stanković, Tijana, Lavrnja, Irena, Podolski-Renić, Ana, Banković, Jasna, Peković, Sanja, Stojiljković, Mirjana, Rakić, Ljubisav, Ruždijić, Sabera, Pešić, Milica, "Purine nucleoside analogs in the therapy of cancer and neuroinflammation" in Molecular inhibitors in targeted therapy, 1, no. 1 (2015):3-14,
https://doi.org/10.1515/motth-2015-0002 . .

TY  - JOUR
AU  - Smiljanić, Kosara
AU  - Pesic, Vesna
AU  - Mladenović, Aleksandra
AU  - Pavković, Željko
AU  - Brkić, Marjana
AU  - Ruždijić, Sabera
AU  - Kanazir, Selma
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2013
AB  - Dietary restriction (DR) exerts significant beneficial effects in terms
   of aging and age-related diseases in many organisms including humans.
   The present study aimed to examine the influence of long-term DR on the
   BDNF system at the transcriptional and translational levels in the
   cortex and hippocampus of middle-aged (12-month-old) and aged
   (24-month-old) male Wistar rats. The obtained results revealed that the
   DR upregulated the expression of exon-specific BDNF transcripts in both
   regions, followed by elevated levels of mBDNF only in the cortex in
   middle-aged animals. In aged animals, DR modulated BDNF protein levels
   by increasing proBDNF and by declining mBDNF levels. Additionally,
   elevated levels of the full-length TrkB accompanied by a decreased level
   of the less-glycosylated TrkB protein were observed in middle-aged rats
   following DR, while in aged rats, DR amplified only the expression of
   the less-glycosylated form of TrkB. The levels of phosphorylated
   TrkB(Y816) were stable during aging regardless of feeding. Reduced
   levels of p75(NTR) were detected in both regions of middle-aged DR-fed
   animals, while a significant increase was measured in the cortex of aged
   DR-fed rats. These findings shed additional light on DR as a modulator
   of BDNF system revealing its disparate effects in middle-aged and aged
   animals. Given the importance of the proBDNF/BDNF circuit-level
   expression in different brain functions and various aspects of behavior,
   it is necessary to further elucidate the optimal duration of the applied
   dietary regimen with regard to the animal age in order to achieve its
   most favorable effects.
T2  - Biogerontology
T1  - Long-term dietary restriction differentially affects the expression of
 BDNF and its receptors in the cortex and hippocampus of middle-aged and
 aged male rats
IS  - 1
VL  - 16
DO  - 10.1007/s10522-014-9537-9
SP  - 71
EP  - 83
ER  - 

@article{
author = "Smiljanić, Kosara and Pesic, Vesna and Mladenović, Aleksandra and Pavković, Željko and Brkić, Marjana and Ruždijić, Sabera and Kanazir, Selma",
year = "2015",
abstract = "Dietary restriction (DR) exerts significant beneficial effects in terms
   of aging and age-related diseases in many organisms including humans.
   The present study aimed to examine the influence of long-term DR on the
   BDNF system at the transcriptional and translational levels in the
   cortex and hippocampus of middle-aged (12-month-old) and aged
   (24-month-old) male Wistar rats. The obtained results revealed that the
   DR upregulated the expression of exon-specific BDNF transcripts in both
   regions, followed by elevated levels of mBDNF only in the cortex in
   middle-aged animals. In aged animals, DR modulated BDNF protein levels
   by increasing proBDNF and by declining mBDNF levels. Additionally,
   elevated levels of the full-length TrkB accompanied by a decreased level
   of the less-glycosylated TrkB protein were observed in middle-aged rats
   following DR, while in aged rats, DR amplified only the expression of
   the less-glycosylated form of TrkB. The levels of phosphorylated
   TrkB(Y816) were stable during aging regardless of feeding. Reduced
   levels of p75(NTR) were detected in both regions of middle-aged DR-fed
   animals, while a significant increase was measured in the cortex of aged
   DR-fed rats. These findings shed additional light on DR as a modulator
   of BDNF system revealing its disparate effects in middle-aged and aged
   animals. Given the importance of the proBDNF/BDNF circuit-level
   expression in different brain functions and various aspects of behavior,
   it is necessary to further elucidate the optimal duration of the applied
   dietary regimen with regard to the animal age in order to achieve its
   most favorable effects.",
journal = "Biogerontology",
title = "Long-term dietary restriction differentially affects the expression of
 BDNF and its receptors in the cortex and hippocampus of middle-aged and
 aged male rats",
number = "1",
volume = "16",
doi = "10.1007/s10522-014-9537-9",
pages = "71-83"
}

Smiljanić, K., Pesic, V., Mladenović, A., Pavković, Ž., Brkić, M., Ruždijić, S.,& Kanazir, S.. (2015). Long-term dietary restriction differentially affects the expression of
 BDNF and its receptors in the cortex and hippocampus of middle-aged and
 aged male rats. in Biogerontology, 16(1), 71-83.
https://doi.org/10.1007/s10522-014-9537-9

Smiljanić K, Pesic V, Mladenović A, Pavković Ž, Brkić M, Ruždijić S, Kanazir S. Long-term dietary restriction differentially affects the expression of
 BDNF and its receptors in the cortex and hippocampus of middle-aged and
 aged male rats. in Biogerontology. 2015;16(1):71-83.
doi:10.1007/s10522-014-9537-9 .

Smiljanić, Kosara, Pesic, Vesna, Mladenović, Aleksandra, Pavković, Željko, Brkić, Marjana, Ruždijić, Sabera, Kanazir, Selma, "Long-term dietary restriction differentially affects the expression of
 BDNF and its receptors in the cortex and hippocampus of middle-aged and
 aged male rats" in Biogerontology, 16, no. 1 (2015):71-83,
https://doi.org/10.1007/s10522-014-9537-9 . .

TY  - JOUR
AU  - Tesic, Vesna
AU  - Perovic, Milka
AU  - Lazic, Divna
AU  - Kojic, Snezana
AU  - Smiljanić, Kosara
AU  - Ruždijić, Sabera
AU  - Rakic, Ljubisav
AU  - Kanazir, Selma
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1967
AB  - Diminished glucocorticoid signaling is associated with an age-related
   decline in hippocampal functioning. In this study we demonstrate the
   effect of intermittent, every other day (EOD) feeding on the
   glucocorticoid hormone/glucocorticoid receptor (GR) system in the
   hippocampus of middle-aged (18-month-old) and aged (24-month-old) Wistar
   rats. In aged ad libitum-fed rats, a decrease in the level of total GR
   and GR phosphorylated at Ser(232) (pGR) was detected. Conversely, aged
   rats subjected to EOD feeding, starting from 6 months of age, showed an
   increase in GR and pGR levels and a higher content of hippocampal
   corticosterone. Furthermore, prominent nuclear staining of pGR was
   observed in CM pyramidal and DG granule neurons of aged EOD-fed rats.
   These changes were accompanied by increased Sglc-1 and decreased GFAP
   transcription, pointing to upregulated transcriptional activity of GR.
   EOD feeding also induced an increase in the expression of the
   mineralocorticoid receptor. Our results reveal that intermittent feeding
   restores impaired GR signaling in the hippocampus of aged animals by
   inducing rather than by stabilizing GR signaling during aging. (C) 2015
   Elsevier Ltd. All rights reserved.
T2  - Journal of Steroid Biochemistry and Molecular Biology
T1  - Long-term intermittent feeding restores impaired GR signaling in the
 hippocampus of aged rat
VL  - 149
DO  - 10.1016/j.jsbmb.2015.01.013
SP  - 43
EP  - 52
ER  - 

@article{
author = "Tesic, Vesna and Perovic, Milka and Lazic, Divna and Kojic, Snezana and Smiljanić, Kosara and Ruždijić, Sabera and Rakic, Ljubisav and Kanazir, Selma",
year = "2015",
abstract = "Diminished glucocorticoid signaling is associated with an age-related
   decline in hippocampal functioning. In this study we demonstrate the
   effect of intermittent, every other day (EOD) feeding on the
   glucocorticoid hormone/glucocorticoid receptor (GR) system in the
   hippocampus of middle-aged (18-month-old) and aged (24-month-old) Wistar
   rats. In aged ad libitum-fed rats, a decrease in the level of total GR
   and GR phosphorylated at Ser(232) (pGR) was detected. Conversely, aged
   rats subjected to EOD feeding, starting from 6 months of age, showed an
   increase in GR and pGR levels and a higher content of hippocampal
   corticosterone. Furthermore, prominent nuclear staining of pGR was
   observed in CM pyramidal and DG granule neurons of aged EOD-fed rats.
   These changes were accompanied by increased Sglc-1 and decreased GFAP
   transcription, pointing to upregulated transcriptional activity of GR.
   EOD feeding also induced an increase in the expression of the
   mineralocorticoid receptor. Our results reveal that intermittent feeding
   restores impaired GR signaling in the hippocampus of aged animals by
   inducing rather than by stabilizing GR signaling during aging. (C) 2015
   Elsevier Ltd. All rights reserved.",
journal = "Journal of Steroid Biochemistry and Molecular Biology",
title = "Long-term intermittent feeding restores impaired GR signaling in the
 hippocampus of aged rat",
volume = "149",
doi = "10.1016/j.jsbmb.2015.01.013",
pages = "43-52"
}

Tesic, V., Perovic, M., Lazic, D., Kojic, S., Smiljanić, K., Ruždijić, S., Rakic, L.,& Kanazir, S.. (2015). Long-term intermittent feeding restores impaired GR signaling in the
 hippocampus of aged rat. in Journal of Steroid Biochemistry and Molecular Biology, 149, 43-52.
https://doi.org/10.1016/j.jsbmb.2015.01.013

Tesic V, Perovic M, Lazic D, Kojic S, Smiljanić K, Ruždijić S, Rakic L, Kanazir S. Long-term intermittent feeding restores impaired GR signaling in the
 hippocampus of aged rat. in Journal of Steroid Biochemistry and Molecular Biology. 2015;149:43-52.
doi:10.1016/j.jsbmb.2015.01.013 .

Tesic, Vesna, Perovic, Milka, Lazic, Divna, Kojic, Snezana, Smiljanić, Kosara, Ruždijić, Sabera, Rakic, Ljubisav, Kanazir, Selma, "Long-term intermittent feeding restores impaired GR signaling in the
 hippocampus of aged rat" in Journal of Steroid Biochemistry and Molecular Biology, 149 (2015):43-52,
https://doi.org/10.1016/j.jsbmb.2015.01.013 . .

TY  - JOUR
AU  - Mladenović, Aleksandra
AU  - Perovic, Milka
AU  - Smiljanić, Kosara
AU  - Todorovic, Smilja
AU  - Tesic, Vesna
AU  - Ruždijić, Sabera
AU  - Kanazir, Selma
PY  - 2014
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2223
AB  - The objective of this study was to examine the effects of aging and
   long-term dietary restriction (DR) on the level of amyloid precursor
   protein (APP) and presenilin-1 (PS-1), proteins that are critically
   involved in Alzheimer's disease. Changes in mRNA and protein expression
   were assessed by real-time PCR and western blot analysis during aging
   and long-term DR in the cortex and hippocampus of 6-, 12-, 18-, and
   24-month-old rats. Prominent regional changes in expression were
   observed in response to aging and DR. Although the hippocampus displayed
   significant alterations in APP mRNA and protein expression and no
   significant changes in PS-1 expression, an opposite pattern was observed
   in the cortex. DR counteracted the age-related changes in APP mRNA
   expression in both structures of old animals. The observed DR-induced
   increase in mRNA levels in the hippocampus was accompanied by an
   increase in the level of full-length protein APP. These results indicate
   that although both structures are very sensitive to aging, a specific
   spatial pattern of changes in APP and PS-1 occurs during aging.
   Furthermore, these findings provide evidence that DR can affect APP and
   PS-1 expression in a manner consistent with its proposed `antiaging'
   effect.
T2  - Neuroreport
T1  - The effects of dietary restriction and aging on amyloid precursor
 protein and presenilin-1 mRNA and protein expression in rat brain
IS  - 6
VL  - 25
DO  - 10.1097/WNR.0000000000000107
SP  - 398
EP  - 403
ER  - 

@article{
author = "Mladenović, Aleksandra and Perovic, Milka and Smiljanić, Kosara and Todorovic, Smilja and Tesic, Vesna and Ruždijić, Sabera and Kanazir, Selma",
year = "2014",
abstract = "The objective of this study was to examine the effects of aging and
   long-term dietary restriction (DR) on the level of amyloid precursor
   protein (APP) and presenilin-1 (PS-1), proteins that are critically
   involved in Alzheimer's disease. Changes in mRNA and protein expression
   were assessed by real-time PCR and western blot analysis during aging
   and long-term DR in the cortex and hippocampus of 6-, 12-, 18-, and
   24-month-old rats. Prominent regional changes in expression were
   observed in response to aging and DR. Although the hippocampus displayed
   significant alterations in APP mRNA and protein expression and no
   significant changes in PS-1 expression, an opposite pattern was observed
   in the cortex. DR counteracted the age-related changes in APP mRNA
   expression in both structures of old animals. The observed DR-induced
   increase in mRNA levels in the hippocampus was accompanied by an
   increase in the level of full-length protein APP. These results indicate
   that although both structures are very sensitive to aging, a specific
   spatial pattern of changes in APP and PS-1 occurs during aging.
   Furthermore, these findings provide evidence that DR can affect APP and
   PS-1 expression in a manner consistent with its proposed `antiaging'
   effect.",
journal = "Neuroreport",
title = "The effects of dietary restriction and aging on amyloid precursor
 protein and presenilin-1 mRNA and protein expression in rat brain",
number = "6",
volume = "25",
doi = "10.1097/WNR.0000000000000107",
pages = "398-403"
}

Mladenović, A., Perovic, M., Smiljanić, K., Todorovic, S., Tesic, V., Ruždijić, S.,& Kanazir, S.. (2014). The effects of dietary restriction and aging on amyloid precursor
 protein and presenilin-1 mRNA and protein expression in rat brain. in Neuroreport, 25(6), 398-403.
https://doi.org/10.1097/WNR.0000000000000107

Mladenović A, Perovic M, Smiljanić K, Todorovic S, Tesic V, Ruždijić S, Kanazir S. The effects of dietary restriction and aging on amyloid precursor
 protein and presenilin-1 mRNA and protein expression in rat brain. in Neuroreport. 2014;25(6):398-403.
doi:10.1097/WNR.0000000000000107 .

Mladenović, Aleksandra, Perovic, Milka, Smiljanić, Kosara, Todorovic, Smilja, Tesic, Vesna, Ruždijić, Sabera, Kanazir, Selma, "The effects of dietary restriction and aging on amyloid precursor
 protein and presenilin-1 mRNA and protein expression in rat brain" in Neuroreport, 25, no. 6 (2014):398-403,
https://doi.org/10.1097/WNR.0000000000000107 . .

TY  - JOUR
AU  - Banković, Jasna Z.
AU  - Joerg, Andrae
AU  - Todorović, Nataša
AU  - Podolski-Renić, Ana
AU  - Milošević, Zorica Z.
AU  - Miljković, Đorđe
AU  - Krause, Jannike
AU  - Ruždijić, Sabera
AU  - Tanić, Nikola
AU  - Pešić, Milica
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1018
AB  - Most chemotherapeutics harm normal cells causing severe side effects and induce the development of resistance in cancer cells. Antimicrobial peptides (AMPs), recognized as anticancer agents, may overcome these limitations. The most studied mechanism underlying multidrug resistance (MDR) is the over-expression of cell membrane transporter P-glycoprotein (P-gp), which extrudes a variety of hydrophobic drugs. Additionally, P-gp contributes to cell membrane composition and increases the net negative charge on cell surface. We postulated that NK-lysin derived cationic peptide NK-2 might discriminate and preferentially eliminate P-gp over-expressing cancer cells. To test this hypothesis, we employed MDR non-small cell lung carcinoma (NCI-H460/R) and colorectal carcinoma (DLD1-TxR) cell lines with high P-gp expression. MDR cancer cells that survived NK-2 treatment had decreased P-gp expression and were more susceptible to doxorubicin. We found that NK-2 more readily eliminated P-gp high-expressing cells. Acting in 'carpet-like' manner NK-2 co-localized with P-gp on the MDR cancer cell membrane. The inhibition of P-gp reduced the NK-2 effect in MDR cancer cells and, vice versa, NK-2 decreased P-gp transport activity. In conclusion, NK-2 could modulate MDR in unique way, eliminating the P-gp high-expressing cells from heterogeneous cancers and making them more vulnerable to classical drug treatment. (C) 2012 Elsevier Inc. All rights reserved.
PB  - Elsevier
T2  - Experimental Cell Research
T1  - The elimination of P-glycoprotein over-expressing cancer cells by antimicrobial cationic peptide NK-2: The unique way of multi-drug resistance modulation
IS  - 7
VL  - 319
DO  - 10.1016/j.yexcr.2012.12.017
SP  - 1013
EP  - 1027
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1018
ER  - 

@article{
author = "Banković, Jasna Z. and Joerg, Andrae and Todorović, Nataša and Podolski-Renić, Ana and Milošević, Zorica Z. and Miljković, Đorđe and Krause, Jannike and Ruždijić, Sabera and Tanić, Nikola and Pešić, Milica",
year = "2013",
abstract = "Most chemotherapeutics harm normal cells causing severe side effects and induce the development of resistance in cancer cells. Antimicrobial peptides (AMPs), recognized as anticancer agents, may overcome these limitations. The most studied mechanism underlying multidrug resistance (MDR) is the over-expression of cell membrane transporter P-glycoprotein (P-gp), which extrudes a variety of hydrophobic drugs. Additionally, P-gp contributes to cell membrane composition and increases the net negative charge on cell surface. We postulated that NK-lysin derived cationic peptide NK-2 might discriminate and preferentially eliminate P-gp over-expressing cancer cells. To test this hypothesis, we employed MDR non-small cell lung carcinoma (NCI-H460/R) and colorectal carcinoma (DLD1-TxR) cell lines with high P-gp expression. MDR cancer cells that survived NK-2 treatment had decreased P-gp expression and were more susceptible to doxorubicin. We found that NK-2 more readily eliminated P-gp high-expressing cells. Acting in 'carpet-like' manner NK-2 co-localized with P-gp on the MDR cancer cell membrane. The inhibition of P-gp reduced the NK-2 effect in MDR cancer cells and, vice versa, NK-2 decreased P-gp transport activity. In conclusion, NK-2 could modulate MDR in unique way, eliminating the P-gp high-expressing cells from heterogeneous cancers and making them more vulnerable to classical drug treatment. (C) 2012 Elsevier Inc. All rights reserved.",
publisher = "Elsevier",
journal = "Experimental Cell Research",
title = "The elimination of P-glycoprotein over-expressing cancer cells by antimicrobial cationic peptide NK-2: The unique way of multi-drug resistance modulation",
number = "7",
volume = "319",
doi = "10.1016/j.yexcr.2012.12.017",
pages = "1013-1027",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1018"
}

Banković, J. Z., Joerg, A., Todorović, N., Podolski-Renić, A., Milošević, Z. Z., Miljković, Đ., Krause, J., Ruždijić, S., Tanić, N.,& Pešić, M.. (2013). The elimination of P-glycoprotein over-expressing cancer cells by antimicrobial cationic peptide NK-2: The unique way of multi-drug resistance modulation. in Experimental Cell Research
Elsevier., 319(7), 1013-1027.
https://doi.org/10.1016/j.yexcr.2012.12.017
https://hdl.handle.net/21.15107/rcub_ibiss_1018

Banković JZ, Joerg A, Todorović N, Podolski-Renić A, Milošević ZZ, Miljković Đ, Krause J, Ruždijić S, Tanić N, Pešić M. The elimination of P-glycoprotein over-expressing cancer cells by antimicrobial cationic peptide NK-2: The unique way of multi-drug resistance modulation. in Experimental Cell Research. 2013;319(7):1013-1027.
doi:10.1016/j.yexcr.2012.12.017
https://hdl.handle.net/21.15107/rcub_ibiss_1018 .

Banković, Jasna Z., Joerg, Andrae, Todorović, Nataša, Podolski-Renić, Ana, Milošević, Zorica Z., Miljković, Đorđe, Krause, Jannike, Ruždijić, Sabera, Tanić, Nikola, Pešić, Milica, "The elimination of P-glycoprotein over-expressing cancer cells by antimicrobial cationic peptide NK-2: The unique way of multi-drug resistance modulation" in Experimental Cell Research, 319, no. 7 (2013):1013-1027,
https://doi.org/10.1016/j.yexcr.2012.12.017 .,
https://hdl.handle.net/21.15107/rcub_ibiss_1018 .

TY  - JOUR
AU  - Lončarević-Vasiljković, Nataša
AU  - Pešić, Vesna
AU  - Tanić, N.
AU  - Milanović, Desanka
AU  - Mladenović, Aleksandra
AU  - Perović, Milka
AU  - Kanazir, Selma
AU  - Ruždijić, Sabera
PY  - 2013
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/328
AB  - The recovery period following cortical injury (CI) is characterized by a dynamic and highly complex interplay between beneficial and detrimental events. The aim of this study was to examine the expressions of Glial Fibrillary Acidic Protein (GFAP), Apolipoprotein E (ApoE) and Amyloid Precursor Protein (APP), all of which are involved in brain plasticity and neurodegeneration. Our results reveal that CI strongly influenced GFAP, ApoE and APP mRNA expression, as well as GFAP and ApoE protein expression. Considering the pivotal role of these proteins in the brain, the obtained results point to their potential contribution in neurodegeneration and consequent Alzheimer's disease development.
T2  - Archives of Biological Sciences
T1  - Changes in expression of GFAP, ApoE and APP mRNA and protein levels in the adult rat brain following cortical injury
IS  - 1
VL  - 65
SP  - 255
EP  - 264
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_328
ER  - 

@article{
author = "Lončarević-Vasiljković, Nataša and Pešić, Vesna and Tanić, N. and Milanović, Desanka and Mladenović, Aleksandra and Perović, Milka and Kanazir, Selma and Ruždijić, Sabera",
year = "2013, 2013",
abstract = "The recovery period following cortical injury (CI) is characterized by a dynamic and highly complex interplay between beneficial and detrimental events. The aim of this study was to examine the expressions of Glial Fibrillary Acidic Protein (GFAP), Apolipoprotein E (ApoE) and Amyloid Precursor Protein (APP), all of which are involved in brain plasticity and neurodegeneration. Our results reveal that CI strongly influenced GFAP, ApoE and APP mRNA expression, as well as GFAP and ApoE protein expression. Considering the pivotal role of these proteins in the brain, the obtained results point to their potential contribution in neurodegeneration and consequent Alzheimer's disease development.",
journal = "Archives of Biological Sciences",
title = "Changes in expression of GFAP, ApoE and APP mRNA and protein levels in the adult rat brain following cortical injury",
number = "1",
volume = "65",
pages = "255-264",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_328"
}

Lončarević-Vasiljković, N., Pešić, V., Tanić, N., Milanović, D., Mladenović, A., Perović, M., Kanazir, S.,& Ruždijić, S.. (2013). Changes in expression of GFAP, ApoE and APP mRNA and protein levels in the adult rat brain following cortical injury. in Archives of Biological Sciences, 65(1), 255-264.
https://hdl.handle.net/21.15107/rcub_ibiss_328

Lončarević-Vasiljković N, Pešić V, Tanić N, Milanović D, Mladenović A, Perović M, Kanazir S, Ruždijić S. Changes in expression of GFAP, ApoE and APP mRNA and protein levels in the adult rat brain following cortical injury. in Archives of Biological Sciences. 2013;65(1):255-264.
https://hdl.handle.net/21.15107/rcub_ibiss_328 .

Lončarević-Vasiljković, Nataša, Pešić, Vesna, Tanić, N., Milanović, Desanka, Mladenović, Aleksandra, Perović, Milka, Kanazir, Selma, Ruždijić, Sabera, "Changes in expression of GFAP, ApoE and APP mRNA and protein levels in the adult rat brain following cortical injury" in Archives of Biological Sciences, 65, no. 1 (2013):255-264,
https://hdl.handle.net/21.15107/rcub_ibiss_328 .

TY  - JOUR
AU  - Perović, Milka
AU  - Tesić, Vesna T
AU  - Mladenović, Aleksandra
AU  - Smiljanić, Kosara
AU  - Lončarević-Vasiljković, Nataša
AU  - Ruždijić, Sabera
AU  - Kanazir, Selma
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/946
AB  - Neurotrophins are established molecular mediators of neuronal plasticity in the adult brain. We analyzed the impact of aging on brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) protein isoforms, their receptors, and on the expression patterns of multiple 5' exon-specific BDNF transcripts in the rat cortex and hippocampus throughout the life span of the rat (6, 12, 18, and 24 months of age). ProNGF was increased during aging in both structures. Mature NGF gradually decreased in the cortex, and, in 24-month-old animals, it was 30 % lower than that in adult 6-month-old rats. The BDNF expression did not change during aging, while proBDNF accumulated in the hippocampus of aged rats. Hippocampal total BDNF mRNA was lower in 12-month-old animals, mostly as a result of a decrease of BDNF transcripts 1 and 2. In contrast to the region-specific regulation of specific exon-containing BDNF mRNAs in adult animals, the same BDNF RNA isoforms (containing exons III, IV, or VI) were present in both brain structures of aged animals. Deficits in neurotrophin signaling were supported by the observed decrease in Trk receptor expression which was accompanied by lower levels of the two main downstream effector kinases, pAkt and protein kinase C. The proteolytic processing of p75NTR observed in 12-month-old rats points to an additional regulatory mechanism in early aging. The changes described herein could contribute to reduced brain plasticity underlying the age-dependent decline in cognitive function.
T2  - Age
T1  - BDNF transcripts, proBDNF and proNGF, in the cortex and hippocampus throughout the life span of the rat
IS  - 6
VL  - 35
SP  - 233
EP  - 2070
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_946
ER  - 

@article{
author = "Perović, Milka and Tesić, Vesna T and Mladenović, Aleksandra and Smiljanić, Kosara and Lončarević-Vasiljković, Nataša and Ruždijić, Sabera and Kanazir, Selma",
year = "2013",
abstract = "Neurotrophins are established molecular mediators of neuronal plasticity in the adult brain. We analyzed the impact of aging on brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) protein isoforms, their receptors, and on the expression patterns of multiple 5' exon-specific BDNF transcripts in the rat cortex and hippocampus throughout the life span of the rat (6, 12, 18, and 24 months of age). ProNGF was increased during aging in both structures. Mature NGF gradually decreased in the cortex, and, in 24-month-old animals, it was 30 % lower than that in adult 6-month-old rats. The BDNF expression did not change during aging, while proBDNF accumulated in the hippocampus of aged rats. Hippocampal total BDNF mRNA was lower in 12-month-old animals, mostly as a result of a decrease of BDNF transcripts 1 and 2. In contrast to the region-specific regulation of specific exon-containing BDNF mRNAs in adult animals, the same BDNF RNA isoforms (containing exons III, IV, or VI) were present in both brain structures of aged animals. Deficits in neurotrophin signaling were supported by the observed decrease in Trk receptor expression which was accompanied by lower levels of the two main downstream effector kinases, pAkt and protein kinase C. The proteolytic processing of p75NTR observed in 12-month-old rats points to an additional regulatory mechanism in early aging. The changes described herein could contribute to reduced brain plasticity underlying the age-dependent decline in cognitive function.",
journal = "Age",
title = "BDNF transcripts, proBDNF and proNGF, in the cortex and hippocampus throughout the life span of the rat",
number = "6",
volume = "35",
pages = "233-2070",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_946"
}

Perović, M., Tesić, V. T., Mladenović, A., Smiljanić, K., Lončarević-Vasiljković, N., Ruždijić, S.,& Kanazir, S.. (2013). BDNF transcripts, proBDNF and proNGF, in the cortex and hippocampus throughout the life span of the rat. in Age, 35(6), 233-2070.
https://hdl.handle.net/21.15107/rcub_ibiss_946

Perović M, Tesić VT, Mladenović A, Smiljanić K, Lončarević-Vasiljković N, Ruždijić S, Kanazir S. BDNF transcripts, proBDNF and proNGF, in the cortex and hippocampus throughout the life span of the rat. in Age. 2013;35(6):233-2070.
https://hdl.handle.net/21.15107/rcub_ibiss_946 .

Perović, Milka, Tesić, Vesna T, Mladenović, Aleksandra, Smiljanić, Kosara, Lončarević-Vasiljković, Nataša, Ruždijić, Sabera, Kanazir, Selma, "BDNF transcripts, proBDNF and proNGF, in the cortex and hippocampus throughout the life span of the rat" in Age, 35, no. 6 (2013):233-2070,
https://hdl.handle.net/21.15107/rcub_ibiss_946 .

TY  - JOUR
AU  - Smiljanić, Kosara
AU  - Vanmierlo, Tim
AU  - Mladenović, Aleksandra
AU  - Perović, Milka
AU  - Lončarević-Vasiljković, Nataša
AU  - Tesić, Vesna T
AU  - Rakić, Ljubisav
AU  - Ruždijić, Sabera
AU  - Lutjohann, Dieter
AU  - Kanazir, Selma
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/953
AB  - Disturbance of cholesterol homeostasis in the brain is coupled to age-related brain dysfunction. In the present work, we studied the relationship between aging and cholesterol metabolism in two brain regions, the cortex and hippocampus, as well as in the sera and liver of 6-, 12-, 18- and 24-month-old male Wistar rats. Using gas chromatography-mass spectrometry, we undertook a comparative analysis of the concentrations of cholesterol, its precursors and metabolites, as well as dietary-derived phytosterols. During aging, the concentrations of the three cholesterol precursors examined (lanosterol, lathosterol and desmosterol) were unchanged in the cortex, except for desmosterol which decreased (44 %) in 18-month-old rats. In the hippocampus, aging was associated with a significant reduction in lanosterol and lathosterol concentrations at 24 months (28 and 25 %, respectively), as well as by a significant decrease of desmosterol concentration at 18 and 24 months (36 and 51 %, respectively). In contrast, in the liver we detected age-induced increases in lanosterol and lathosterol concentrations, and no change in desmosterol concentration. The amounts of these sterols were lower than in the brain regions. In the cortex and hippocampus, desmosterol was the predominant cholesterol precursor. In the liver, lathosterol was the most abundant precursor. This ratio remained stable during aging. The most striking effect of aging observed in our study was a significant decrease in desmosterol concentration in the hippocampus which could reflect age-related reduced synaptic plasticity, thus representing one of the detrimental effects of advanced age.
T2  - Lipids
T1  - Aging Induces Tissue-Specific Changes in Cholesterol Metabolism in Rat Brain and Liver
IS  - 11
VL  - 48
SP  - 5
EP  - 1077
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_953
ER  - 

@article{
author = "Smiljanić, Kosara and Vanmierlo, Tim and Mladenović, Aleksandra and Perović, Milka and Lončarević-Vasiljković, Nataša and Tesić, Vesna T and Rakić, Ljubisav and Ruždijić, Sabera and Lutjohann, Dieter and Kanazir, Selma",
year = "2013",
abstract = "Disturbance of cholesterol homeostasis in the brain is coupled to age-related brain dysfunction. In the present work, we studied the relationship between aging and cholesterol metabolism in two brain regions, the cortex and hippocampus, as well as in the sera and liver of 6-, 12-, 18- and 24-month-old male Wistar rats. Using gas chromatography-mass spectrometry, we undertook a comparative analysis of the concentrations of cholesterol, its precursors and metabolites, as well as dietary-derived phytosterols. During aging, the concentrations of the three cholesterol precursors examined (lanosterol, lathosterol and desmosterol) were unchanged in the cortex, except for desmosterol which decreased (44 %) in 18-month-old rats. In the hippocampus, aging was associated with a significant reduction in lanosterol and lathosterol concentrations at 24 months (28 and 25 %, respectively), as well as by a significant decrease of desmosterol concentration at 18 and 24 months (36 and 51 %, respectively). In contrast, in the liver we detected age-induced increases in lanosterol and lathosterol concentrations, and no change in desmosterol concentration. The amounts of these sterols were lower than in the brain regions. In the cortex and hippocampus, desmosterol was the predominant cholesterol precursor. In the liver, lathosterol was the most abundant precursor. This ratio remained stable during aging. The most striking effect of aging observed in our study was a significant decrease in desmosterol concentration in the hippocampus which could reflect age-related reduced synaptic plasticity, thus representing one of the detrimental effects of advanced age.",
journal = "Lipids",
title = "Aging Induces Tissue-Specific Changes in Cholesterol Metabolism in Rat Brain and Liver",
number = "11",
volume = "48",
pages = "5-1077",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_953"
}

Smiljanić, K., Vanmierlo, T., Mladenović, A., Perović, M., Lončarević-Vasiljković, N., Tesić, V. T., Rakić, L., Ruždijić, S., Lutjohann, D.,& Kanazir, S.. (2013). Aging Induces Tissue-Specific Changes in Cholesterol Metabolism in Rat Brain and Liver. in Lipids, 48(11), 5-1077.
https://hdl.handle.net/21.15107/rcub_ibiss_953

Smiljanić K, Vanmierlo T, Mladenović A, Perović M, Lončarević-Vasiljković N, Tesić VT, Rakić L, Ruždijić S, Lutjohann D, Kanazir S. Aging Induces Tissue-Specific Changes in Cholesterol Metabolism in Rat Brain and Liver. in Lipids. 2013;48(11):5-1077.
https://hdl.handle.net/21.15107/rcub_ibiss_953 .

Smiljanić, Kosara, Vanmierlo, Tim, Mladenović, Aleksandra, Perović, Milka, Lončarević-Vasiljković, Nataša, Tesić, Vesna T, Rakić, Ljubisav, Ruždijić, Sabera, Lutjohann, Dieter, Kanazir, Selma, "Aging Induces Tissue-Specific Changes in Cholesterol Metabolism in Rat Brain and Liver" in Lipids, 48, no. 11 (2013):5-1077,
https://hdl.handle.net/21.15107/rcub_ibiss_953 .

TY  - JOUR
AU  - Milinković, Vedrana P.
AU  - Banković, Jasna Z.
AU  - Rakić, Miodrag L
AU  - Stanković, Tijana
AU  - Skender-Gazibara, Milica K
AU  - Ruždijić, Sabera
AU  - Tanić, Nikola T
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/938
AB  - Glioblastoma is the most frequent and malignant human brain tumor. High level of genomic instability detected in glioma cells implies that numerous genetic alterations accumulate during glioma pathogenesis. We investigated alterations in AP-PCR DNA profiles of 30 glioma patients, and detected specific changes in 11 genes not previously associated with this disease: LHFPL3, SGCG, HTR4, ITGB1, CPS1, PROS1, GP2, KCNG2, PDE4D, KIR3DL3, and INPP5A. Further correlations revealed that 8 genes might play important role in pathogenesis of glial tumors, while changes in GP2, KCNG2 and KIR3DL3 should be considered as passenger mutations, consequence of high level of genomic instability. Identified genes have a significant role in signal transduction or cell adhesion, which are important processes for cancer development and progression. According to our results, LHFPL3 might be characteristic of primary glioblastoma, SGCG, HTR4, ITGB1, CPS1, PROS1 and INPP5A were detected predominantly in anaplastic astrocytoma, suggesting their role in progression of secondary glioblastoma, while alterations of PDE4D seem to have important role in development of both glioblastoma subtypes. Some of the identified genes showed significant association with p53, p16, and EGFR, but there was no significant correlation between loss of PTEN and any of identified genes. In conclusion our study revealed genetic alterations that were not previously associated with glioma pathogenesis and could be potentially used as molecular markers of different glioblastoma subtypes.
T2  - Plos One
T1  - Identification of Novel Genetic Alterations in Samples of Malignant Glioma Patients
IS  - 12
VL  - 8
SP  - 977
EP  - na
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_938
ER  - 

@article{
author = "Milinković, Vedrana P. and Banković, Jasna Z. and Rakić, Miodrag L and Stanković, Tijana and Skender-Gazibara, Milica K and Ruždijić, Sabera and Tanić, Nikola T",
year = "2013",
abstract = "Glioblastoma is the most frequent and malignant human brain tumor. High level of genomic instability detected in glioma cells implies that numerous genetic alterations accumulate during glioma pathogenesis. We investigated alterations in AP-PCR DNA profiles of 30 glioma patients, and detected specific changes in 11 genes not previously associated with this disease: LHFPL3, SGCG, HTR4, ITGB1, CPS1, PROS1, GP2, KCNG2, PDE4D, KIR3DL3, and INPP5A. Further correlations revealed that 8 genes might play important role in pathogenesis of glial tumors, while changes in GP2, KCNG2 and KIR3DL3 should be considered as passenger mutations, consequence of high level of genomic instability. Identified genes have a significant role in signal transduction or cell adhesion, which are important processes for cancer development and progression. According to our results, LHFPL3 might be characteristic of primary glioblastoma, SGCG, HTR4, ITGB1, CPS1, PROS1 and INPP5A were detected predominantly in anaplastic astrocytoma, suggesting their role in progression of secondary glioblastoma, while alterations of PDE4D seem to have important role in development of both glioblastoma subtypes. Some of the identified genes showed significant association with p53, p16, and EGFR, but there was no significant correlation between loss of PTEN and any of identified genes. In conclusion our study revealed genetic alterations that were not previously associated with glioma pathogenesis and could be potentially used as molecular markers of different glioblastoma subtypes.",
journal = "Plos One",
title = "Identification of Novel Genetic Alterations in Samples of Malignant Glioma Patients",
number = "12",
volume = "8",
pages = "977-na",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_938"
}

Milinković, V. P., Banković, J. Z., Rakić, M. L., Stanković, T., Skender-Gazibara, M. K., Ruždijić, S.,& Tanić, N. T.. (2013). Identification of Novel Genetic Alterations in Samples of Malignant Glioma Patients. in Plos One, 8(12), 977-na.
https://hdl.handle.net/21.15107/rcub_ibiss_938

Milinković VP, Banković JZ, Rakić ML, Stanković T, Skender-Gazibara MK, Ruždijić S, Tanić NT. Identification of Novel Genetic Alterations in Samples of Malignant Glioma Patients. in Plos One. 2013;8(12):977-na.
https://hdl.handle.net/21.15107/rcub_ibiss_938 .

Milinković, Vedrana P., Banković, Jasna Z., Rakić, Miodrag L, Stanković, Tijana, Skender-Gazibara, Milica K, Ruždijić, Sabera, Tanić, Nikola T, "Identification of Novel Genetic Alterations in Samples of Malignant Glioma Patients" in Plos One, 8, no. 12 (2013):977-na,
https://hdl.handle.net/21.15107/rcub_ibiss_938 .

TY  - JOUR
AU  - Popić, Jelena
AU  - Pešić, Vesna
AU  - Milanović, Desanka
AU  - Todorović, Smilja
AU  - Kanazir, Selma
AU  - Jevtović-Todorović, Vesna
AU  - Ruždijić, Sabera
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4125
AB  - Several studies have revealed a role for neurotrophins in anesthesia-induced neurotoxicity in the developing brain. In this study we monitored the spatial and temporal expression of neurotrophic signaling molecules in the brain of 14-day-old (PND14) Wistar rats after the application of a single propofol dose (25 mg/kg i.p). The structures of interest were the cortex and thalamus as the primary areas of anesthetic actions. Changes of the protein levels of the brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), their activated receptors tropomyosin-related kinase (TrkA and TrkB) and downstream kinases Akt and the extracellular signal regulated kinase (ERK) were assessed by Western immunoblot analysis at different time points during the first 24 h after the treatment, as well as the expression of cleaved caspase-3 fragment. Fluoro-Jade B staining was used to follow the appearance of degenerating neurons. The obtained results show that the treatment caused marked alterations in levels of the examined neurotrophins, their receptors and downstream effector kinases. However, these changes were not associated with increased neurodegeneration in either the cortex or the thalamus. These results indicate that in the brain of PND14 rats, the interaction between Akt/ERK signaling might be one of important part of endogenous defense mechanisms, which the developing brain utilizes to protect itself from potential anesthesia-induced damage. Elucidation of the underlying molecular mechanisms will improve our understanding of the age-dependent component of anesthesia-induced neurotoxicity.
PB  - San Francisco:the Public Library of Science (PLOS)
T2  - PLoS One
T1  - Propofol-induced changes in neurotrophic signaling in the developing nervous system in vivo
IS  - 4
VL  - 7
DO  - 10.1371/journal.pone.0034396
SP  - e34396
ER  - 

@article{
author = "Popić, Jelena and Pešić, Vesna and Milanović, Desanka and Todorović, Smilja and Kanazir, Selma and Jevtović-Todorović, Vesna and Ruždijić, Sabera",
year = "2012",
abstract = "Several studies have revealed a role for neurotrophins in anesthesia-induced neurotoxicity in the developing brain. In this study we monitored the spatial and temporal expression of neurotrophic signaling molecules in the brain of 14-day-old (PND14) Wistar rats after the application of a single propofol dose (25 mg/kg i.p). The structures of interest were the cortex and thalamus as the primary areas of anesthetic actions. Changes of the protein levels of the brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), their activated receptors tropomyosin-related kinase (TrkA and TrkB) and downstream kinases Akt and the extracellular signal regulated kinase (ERK) were assessed by Western immunoblot analysis at different time points during the first 24 h after the treatment, as well as the expression of cleaved caspase-3 fragment. Fluoro-Jade B staining was used to follow the appearance of degenerating neurons. The obtained results show that the treatment caused marked alterations in levels of the examined neurotrophins, their receptors and downstream effector kinases. However, these changes were not associated with increased neurodegeneration in either the cortex or the thalamus. These results indicate that in the brain of PND14 rats, the interaction between Akt/ERK signaling might be one of important part of endogenous defense mechanisms, which the developing brain utilizes to protect itself from potential anesthesia-induced damage. Elucidation of the underlying molecular mechanisms will improve our understanding of the age-dependent component of anesthesia-induced neurotoxicity.",
publisher = "San Francisco:the Public Library of Science (PLOS)",
journal = "PLoS One",
title = "Propofol-induced changes in neurotrophic signaling in the developing nervous system in vivo",
number = "4",
volume = "7",
doi = "10.1371/journal.pone.0034396",
pages = "e34396"
}

Popić, J., Pešić, V., Milanović, D., Todorović, S., Kanazir, S., Jevtović-Todorović, V.,& Ruždijić, S.. (2012). Propofol-induced changes in neurotrophic signaling in the developing nervous system in vivo. in PLoS One
San Francisco:the Public Library of Science (PLOS)., 7(4), e34396.
https://doi.org/10.1371/journal.pone.0034396

Popić J, Pešić V, Milanović D, Todorović S, Kanazir S, Jevtović-Todorović V, Ruždijić S. Propofol-induced changes in neurotrophic signaling in the developing nervous system in vivo. in PLoS One. 2012;7(4):e34396.
doi:10.1371/journal.pone.0034396 .

Popić, Jelena, Pešić, Vesna, Milanović, Desanka, Todorović, Smilja, Kanazir, Selma, Jevtović-Todorović, Vesna, Ruždijić, Sabera, "Propofol-induced changes in neurotrophic signaling in the developing nervous system in vivo" in PLoS One, 7, no. 4 (2012):e34396,
https://doi.org/10.1371/journal.pone.0034396 . .

TY  - JOUR
AU  - Lončarević-Vasiljković, Nataša
AU  - Pešić, Vesna
AU  - Todorović, Smilja
AU  - Popić, Jelena
AU  - Smiljanić, Kosara
AU  - Milanović, Desanka
AU  - Ruždijić, Sabera
AU  - Kanazir, Selma
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4134
AB  - Traumatic brain injury (TBI) is a widespread cause of death and a major source of adult disability. Subsequent pathological events occurring in the brain after TBI, referred to as secondary injury, continue to damage surrounding tissue resulting in substantial neuronal loss. One of the hallmarks of the secondary injury process is microglial activation resulting in increased cytokine production. Notwithstanding that recent studies demonstrated that caloric restriction (CR) lasting several months prior to an acute TBI exhibits neuroprotective properties, understanding how exactly CR influences secondary injury is still unclear. The goal of the present study was to examine whether CR (50% of daily food intake for 3 months) alleviates the effects of secondary injury on neuronal loss following cortical stab injury (CSI). To this end, we examined the effects of CR on the microglial activation, tumor necrosis factor-α (TNF-α) and caspase-3 expression in the ipsilateral (injured) cortex of the adult rats during the recovery period (from 2 to 28 days) after injury. Our results demonstrate that CR prior to CSI suppresses microglial activation, induction of TNF-α and caspase-3, as well as neurodegeneration following injury. These results indicate that CR strongly attenuates the effects of secondary injury, thus suggesting that CR may increase the successful outcome following TBI.
PB  - San Francisco:the Public Library of Science (PLOS)
T2  - PLoS One
T1  - Caloric restriction suppresses microglial activation and prevents neuroapoptosis following cortical injury in rats
IS  - 5
VL  - 7
DO  - 10.1371/journal.pone.0037215
SP  - e37215
ER  - 

@article{
author = "Lončarević-Vasiljković, Nataša and Pešić, Vesna and Todorović, Smilja and Popić, Jelena and Smiljanić, Kosara and Milanović, Desanka and Ruždijić, Sabera and Kanazir, Selma",
year = "2012",
abstract = "Traumatic brain injury (TBI) is a widespread cause of death and a major source of adult disability. Subsequent pathological events occurring in the brain after TBI, referred to as secondary injury, continue to damage surrounding tissue resulting in substantial neuronal loss. One of the hallmarks of the secondary injury process is microglial activation resulting in increased cytokine production. Notwithstanding that recent studies demonstrated that caloric restriction (CR) lasting several months prior to an acute TBI exhibits neuroprotective properties, understanding how exactly CR influences secondary injury is still unclear. The goal of the present study was to examine whether CR (50% of daily food intake for 3 months) alleviates the effects of secondary injury on neuronal loss following cortical stab injury (CSI). To this end, we examined the effects of CR on the microglial activation, tumor necrosis factor-α (TNF-α) and caspase-3 expression in the ipsilateral (injured) cortex of the adult rats during the recovery period (from 2 to 28 days) after injury. Our results demonstrate that CR prior to CSI suppresses microglial activation, induction of TNF-α and caspase-3, as well as neurodegeneration following injury. These results indicate that CR strongly attenuates the effects of secondary injury, thus suggesting that CR may increase the successful outcome following TBI.",
publisher = "San Francisco:the Public Library of Science (PLOS)",
journal = "PLoS One",
title = "Caloric restriction suppresses microglial activation and prevents neuroapoptosis following cortical injury in rats",
number = "5",
volume = "7",
doi = "10.1371/journal.pone.0037215",
pages = "e37215"
}

Lončarević-Vasiljković, N., Pešić, V., Todorović, S., Popić, J., Smiljanić, K., Milanović, D., Ruždijić, S.,& Kanazir, S.. (2012). Caloric restriction suppresses microglial activation and prevents neuroapoptosis following cortical injury in rats. in PLoS One
San Francisco:the Public Library of Science (PLOS)., 7(5), e37215.
https://doi.org/10.1371/journal.pone.0037215

Lončarević-Vasiljković N, Pešić V, Todorović S, Popić J, Smiljanić K, Milanović D, Ruždijić S, Kanazir S. Caloric restriction suppresses microglial activation and prevents neuroapoptosis following cortical injury in rats. in PLoS One. 2012;7(5):e37215.
doi:10.1371/journal.pone.0037215 .

Lončarević-Vasiljković, Nataša, Pešić, Vesna, Todorović, Smilja, Popić, Jelena, Smiljanić, Kosara, Milanović, Desanka, Ruždijić, Sabera, Kanazir, Selma, "Caloric restriction suppresses microglial activation and prevents neuroapoptosis following cortical injury in rats" in PLoS One, 7, no. 5 (2012):e37215,
https://doi.org/10.1371/journal.pone.0037215 . .

TY  - CONF
AU  - Ruždijić, Sabera
AU  - Banković, Jasna Z.
AU  - Podolski-Renić, Ana
AU  - Pešić, Milica
AU  - Milošević, Zorica Z.
AU  - Tanić, Nikola T
AU  - Andra, J
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1161
C3  - European Journal of Cancer
T1  - NK-lysin Derived Peptide (NK-2) Sensitizes Resistant Cancer Cells to Classic Chemotherapeutics by Selective Killing of P-glycoprotein Over-expressing Cells
IS  - null
VL  - 48
EP  - S225
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1161
ER  - 

@conference{
author = "Ruždijić, Sabera and Banković, Jasna Z. and Podolski-Renić, Ana and Pešić, Milica and Milošević, Zorica Z. and Tanić, Nikola T and Andra, J",
year = "2012",
journal = "European Journal of Cancer",
title = "NK-lysin Derived Peptide (NK-2) Sensitizes Resistant Cancer Cells to Classic Chemotherapeutics by Selective Killing of P-glycoprotein Over-expressing Cells",
number = "null",
volume = "48",
pages = "S225",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1161"
}

Ruždijić, S., Banković, J. Z., Podolski-Renić, A., Pešić, M., Milošević, Z. Z., Tanić, N. T.,& Andra, J.. (2012). NK-lysin Derived Peptide (NK-2) Sensitizes Resistant Cancer Cells to Classic Chemotherapeutics by Selective Killing of P-glycoprotein Over-expressing Cells. in European Journal of Cancer, 48(null).
https://hdl.handle.net/21.15107/rcub_ibiss_1161

Ruždijić S, Banković JZ, Podolski-Renić A, Pešić M, Milošević ZZ, Tanić NT, Andra J. NK-lysin Derived Peptide (NK-2) Sensitizes Resistant Cancer Cells to Classic Chemotherapeutics by Selective Killing of P-glycoprotein Over-expressing Cells. in European Journal of Cancer. 2012;48(null):null-S225.
https://hdl.handle.net/21.15107/rcub_ibiss_1161 .

Ruždijić, Sabera, Banković, Jasna Z., Podolski-Renić, Ana, Pešić, Milica, Milošević, Zorica Z., Tanić, Nikola T, Andra, J, "NK-lysin Derived Peptide (NK-2) Sensitizes Resistant Cancer Cells to Classic Chemotherapeutics by Selective Killing of P-glycoprotein Over-expressing Cells" in European Journal of Cancer, 48, no. null (2012),
https://hdl.handle.net/21.15107/rcub_ibiss_1161 .

TY  - JOUR
AU  - Milinković, Vedrana P.
AU  - Banković, Jasna Z.
AU  - Rakić, Miodrag L
AU  - Milosević, Nebojsa T
AU  - Stanković, Tijana
AU  - Joković, Milos B
AU  - Milošević, Zorica Z.
AU  - Skender-Gazibara, Milica K
AU  - Podolski-Renić, Ana
AU  - Pešić, Milica
AU  - Ruždijić, Sabera
AU  - Tanić, Nikola T
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1108
AB  - The purpose of this study was to detect the level of genomic instability and p53 alterations in anaplastic astrocytoma and primary glioblastoma patients, and to evaluate their impact on glioma pathogenesis and patients outcome. AP-PCR DNA profiling revealed two types of genetic differences between tumor and normal tissue: qualitative changes which represent accumulation of changes in DNA sequence and are the manifestation of microsatellite and point mutation instability (MIN-PIN) and quantitative changes which represent amplifications or deletions of existing chromosomal material and are the manifestation of chromosomal instability (CIN). Both types of alterations were present in all analyzed samples contributing almost equally to the total level of genomic instability, and showing no differences between histological subtypes. p53 alterations were detected in 40% of samples, predominantly in anaplastic astrocytoma. The higher level of genomic instability was observed in elderly patients (>50 years) and patents with primary glioblastoma. Level of genomic instability had no impact on patients' survival, while presence of p53 alterations seemed to be a favorable prognostic factor in this case. Our results indicate that extensive genomic instability is one of the main features of malignant gliomas. (C) 2012 Elsevier Inc. All rights reserved.
T2  - Experimental and Molecular Pathology
T1  - Genomic instability and p53 alterations in patients with malignant glioma
IS  - 2
VL  - 93
SP  - 67
EP  - 206
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1108
ER  - 

@article{
author = "Milinković, Vedrana P. and Banković, Jasna Z. and Rakić, Miodrag L and Milosević, Nebojsa T and Stanković, Tijana and Joković, Milos B and Milošević, Zorica Z. and Skender-Gazibara, Milica K and Podolski-Renić, Ana and Pešić, Milica and Ruždijić, Sabera and Tanić, Nikola T",
year = "2012",
abstract = "The purpose of this study was to detect the level of genomic instability and p53 alterations in anaplastic astrocytoma and primary glioblastoma patients, and to evaluate their impact on glioma pathogenesis and patients outcome. AP-PCR DNA profiling revealed two types of genetic differences between tumor and normal tissue: qualitative changes which represent accumulation of changes in DNA sequence and are the manifestation of microsatellite and point mutation instability (MIN-PIN) and quantitative changes which represent amplifications or deletions of existing chromosomal material and are the manifestation of chromosomal instability (CIN). Both types of alterations were present in all analyzed samples contributing almost equally to the total level of genomic instability, and showing no differences between histological subtypes. p53 alterations were detected in 40% of samples, predominantly in anaplastic astrocytoma. The higher level of genomic instability was observed in elderly patients (>50 years) and patents with primary glioblastoma. Level of genomic instability had no impact on patients' survival, while presence of p53 alterations seemed to be a favorable prognostic factor in this case. Our results indicate that extensive genomic instability is one of the main features of malignant gliomas. (C) 2012 Elsevier Inc. All rights reserved.",
journal = "Experimental and Molecular Pathology",
title = "Genomic instability and p53 alterations in patients with malignant glioma",
number = "2",
volume = "93",
pages = "67-206",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1108"
}

Milinković, V. P., Banković, J. Z., Rakić, M. L., Milosević, N. T., Stanković, T., Joković, M. B., Milošević, Z. Z., Skender-Gazibara, M. K., Podolski-Renić, A., Pešić, M., Ruždijić, S.,& Tanić, N. T.. (2012). Genomic instability and p53 alterations in patients with malignant glioma. in Experimental and Molecular Pathology, 93(2), 67-206.
https://hdl.handle.net/21.15107/rcub_ibiss_1108

Milinković VP, Banković JZ, Rakić ML, Milosević NT, Stanković T, Joković MB, Milošević ZZ, Skender-Gazibara MK, Podolski-Renić A, Pešić M, Ruždijić S, Tanić NT. Genomic instability and p53 alterations in patients with malignant glioma. in Experimental and Molecular Pathology. 2012;93(2):67-206.
https://hdl.handle.net/21.15107/rcub_ibiss_1108 .

Milinković, Vedrana P., Banković, Jasna Z., Rakić, Miodrag L, Milosević, Nebojsa T, Stanković, Tijana, Joković, Milos B, Milošević, Zorica Z., Skender-Gazibara, Milica K, Podolski-Renić, Ana, Pešić, Milica, Ruždijić, Sabera, Tanić, Nikola T, "Genomic instability and p53 alterations in patients with malignant glioma" in Experimental and Molecular Pathology, 93, no. 2 (2012):67-206,
https://hdl.handle.net/21.15107/rcub_ibiss_1108 .

TY  - JOUR
AU  - Mladenović, Aleksandra
AU  - Žunić-Božinovski, Snežana
AU  - Kanazir, Selma
AU  - Žunić, Svetlana
AU  - Ruždijić, Sabera
PY  - 2011
PY  - 2011
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/476
AB  - In order to better understand pathogenesis of pulmonary emphysema, the model of experimentally induced pulmonary emphysema in Chinchilla rabbits was used for the estimation of apoptotic clearance of pulmonary tissue. Bronchoalveolar lavage was performed in three groups of animals: experimental group-E on hypercholesterolemic diet (4% edible oil solution of crystalline cholesterol), control group-C1 on standard diet for that animal species and animals on oily diet-C2. Apoptotic detection in cytocentrifuge preparations of lung washings was evaluated by in situ TUNEL. The property of alveolar macrophages to engulf apoptotic cells was estimated by light microscopy including 300 features (related subsequent steps: adsorption, internalization and intracellular processing of free apoptotic bodies) and was evaluated by scoring and indexing method. Internalization of apoptotic bodies by alveolar macrophages, as well as free apoptotic bodies were decreased in E compared to both C1 and C2 group (p<0.01 and p<0.05 respectively). Intracellular processing of apoptotic bodies by alveolar macrophages is significantly decreased in C2 in comparison with E (p<0.05) and C1 group (p<0.01). Apoptotic capacity of pulmonary tissue is significantly decreased in C2 in comparison with C1 group (p<0.01). The results implicate that immuno-metabolic competence of pulmonary tissue might be essentially associated with tissue remodeling in pulmonary emphysema.
AB  - U cilju boljeg razumevanja patogeneze plućnog emfizema, u radu je korišć en eksperimentalni model emfizema pluća na činčila kunićima za procenu apoptotskog kapaciteta plućnoga tkiva. Bronholaveolarna lavaža je urađena na tri grupe životinja: eksperimentalnoj grupi-E na hiperholesterolskoj dijeti (4% uljani rastvor kristalnog holesterola), kontrolnoj grupi-C1 na standardnoj dijeti za tu životinjsku vrstu i grupi životinja na uljanoj dijeti-C2. Određivanje apoptotskih parametara cito-centrifužnih preparata bronhoalveolarnog lavata vršeno je posle bojenja preparata TUNEL in situ citohemijskim metodom. Sposobnost alveolarnih makrofaga da odstrane apoptotske ćelije fagocitozom procenjivana je svetlosnom mikroskopijom na 300 prikaza po preparatu (prikazi uključuju: adsorpciju, internalizaciju i intracelularno procesiranje apoptotskih tela) i evaluirana metodom indeksiranja i skora. Internalizacija apoptotskih tela alveolarnim makrofazima, kao i relativni procenat slobodnih apoptotskih tela, bili su signifikantno smanjeni u E grupi poredeći sa C1 (p<0.01) i C2 grupom (p<0.05). Intracelularno procesiranje apoptotskih tela alveolarnim makrofazima bilo je signifikantno smanjeno u C2 u odnosu na E (p<0.05) i C1 grupu (p<0.01). Apoptotski kapacitet tkiva pluća bio je signifikantno smanjen u C2 u poređenju sa C1 grupom (p<0.01). Ovi rezultati ukazuju da imuno-metabolička kompetentnost plućnog tkiva može biti suštinski povezana sa remodelovanjem tkiva pluća u eksperimentalnom emfizemu pluća.
T2  - Acta veterinaria
T1  - Apoptotski kapacitet u kunića sa eksperimentalnim emfizemom pluća
T1  - Apoptotic clearance in rabbits with experimental pulmonary emphysema
IS  - 5-6
VL  - 61
SP  - 513
EP  - 522
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_476
ER  - 

@article{
author = "Mladenović, Aleksandra and Žunić-Božinovski, Snežana and Kanazir, Selma and Žunić, Svetlana and Ruždijić, Sabera",
year = "2011, 2011",
abstract = "In order to better understand pathogenesis of pulmonary emphysema, the model of experimentally induced pulmonary emphysema in Chinchilla rabbits was used for the estimation of apoptotic clearance of pulmonary tissue. Bronchoalveolar lavage was performed in three groups of animals: experimental group-E on hypercholesterolemic diet (4% edible oil solution of crystalline cholesterol), control group-C1 on standard diet for that animal species and animals on oily diet-C2. Apoptotic detection in cytocentrifuge preparations of lung washings was evaluated by in situ TUNEL. The property of alveolar macrophages to engulf apoptotic cells was estimated by light microscopy including 300 features (related subsequent steps: adsorption, internalization and intracellular processing of free apoptotic bodies) and was evaluated by scoring and indexing method. Internalization of apoptotic bodies by alveolar macrophages, as well as free apoptotic bodies were decreased in E compared to both C1 and C2 group (p<0.01 and p<0.05 respectively). Intracellular processing of apoptotic bodies by alveolar macrophages is significantly decreased in C2 in comparison with E (p<0.05) and C1 group (p<0.01). Apoptotic capacity of pulmonary tissue is significantly decreased in C2 in comparison with C1 group (p<0.01). The results implicate that immuno-metabolic competence of pulmonary tissue might be essentially associated with tissue remodeling in pulmonary emphysema., U cilju boljeg razumevanja patogeneze plućnog emfizema, u radu je korišć en eksperimentalni model emfizema pluća na činčila kunićima za procenu apoptotskog kapaciteta plućnoga tkiva. Bronholaveolarna lavaža je urađena na tri grupe životinja: eksperimentalnoj grupi-E na hiperholesterolskoj dijeti (4% uljani rastvor kristalnog holesterola), kontrolnoj grupi-C1 na standardnoj dijeti za tu životinjsku vrstu i grupi životinja na uljanoj dijeti-C2. Određivanje apoptotskih parametara cito-centrifužnih preparata bronhoalveolarnog lavata vršeno je posle bojenja preparata TUNEL in situ citohemijskim metodom. Sposobnost alveolarnih makrofaga da odstrane apoptotske ćelije fagocitozom procenjivana je svetlosnom mikroskopijom na 300 prikaza po preparatu (prikazi uključuju: adsorpciju, internalizaciju i intracelularno procesiranje apoptotskih tela) i evaluirana metodom indeksiranja i skora. Internalizacija apoptotskih tela alveolarnim makrofazima, kao i relativni procenat slobodnih apoptotskih tela, bili su signifikantno smanjeni u E grupi poredeći sa C1 (p<0.01) i C2 grupom (p<0.05). Intracelularno procesiranje apoptotskih tela alveolarnim makrofazima bilo je signifikantno smanjeno u C2 u odnosu na E (p<0.05) i C1 grupu (p<0.01). Apoptotski kapacitet tkiva pluća bio je signifikantno smanjen u C2 u poređenju sa C1 grupom (p<0.01). Ovi rezultati ukazuju da imuno-metabolička kompetentnost plućnog tkiva može biti suštinski povezana sa remodelovanjem tkiva pluća u eksperimentalnom emfizemu pluća.",
journal = "Acta veterinaria",
title = "Apoptotski kapacitet u kunića sa eksperimentalnim emfizemom pluća, Apoptotic clearance in rabbits with experimental pulmonary emphysema",
number = "5-6",
volume = "61",
pages = "513-522",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_476"
}

Mladenović, A., Žunić-Božinovski, S., Kanazir, S., Žunić, S.,& Ruždijić, S.. (2011). Apoptotski kapacitet u kunića sa eksperimentalnim emfizemom pluća. in Acta veterinaria, 61(5-6), 513-522.
https://hdl.handle.net/21.15107/rcub_ibiss_476

Mladenović A, Žunić-Božinovski S, Kanazir S, Žunić S, Ruždijić S. Apoptotski kapacitet u kunića sa eksperimentalnim emfizemom pluća. in Acta veterinaria. 2011;61(5-6):513-522.
https://hdl.handle.net/21.15107/rcub_ibiss_476 .

Mladenović, Aleksandra, Žunić-Božinovski, Snežana, Kanazir, Selma, Žunić, Svetlana, Ruždijić, Sabera, "Apoptotski kapacitet u kunića sa eksperimentalnim emfizemom pluća" in Acta veterinaria, 61, no. 5-6 (2011):513-522,
https://hdl.handle.net/21.15107/rcub_ibiss_476 .

TY  - JOUR
AU  - Mladenović, Aleksandra
AU  - Perović, Milka
AU  - Tesić, Vesna T
AU  - Tanić, Nikola T
AU  - Rakić, Ljubisav
AU  - Ruždijić, Sabera
AU  - Kanazir, Selma
PY  - 2010
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1414
AB  - Brain aging is related to the numerous structural and functional changes including decreased synaptic plasticity. The beneficial effects of dietary restriction (DR) are well known but insufficiently investigated at the level of plasticity-related markers. Therefore, the aim of this study was to examine the expression profiles of proteins structurally and functionally related to synapses-growth-associated protein 43 (GAP-43), synaptophysin (SPH) and alpha-synuclein (alpha-Syn), in the course of aging and in response to long-term DR. The mRNA and protein levels of three presynaptic proteins were assessed by Real Time RT-PCR and Western blotting in the cortex and hippocampus of young (6-month-old), middle-aged (12-month-old), aged (18-month-old) and old (24-month-old) male Wistar rats fed ad libitum and exposed to DR starting from 6 months of age. We observed that long-term DR modulated age-related transcriptional changes by maintaining stable mRNAs levels in the cortex. No major age-related changes of the protein levels were observed in the cortex, while the specific temporal decline was detected in the hippocampus for all three proteins. The SPH levels were decreased across lifespan (0.8-, 0.8- and 0.6-fold change at 12,18 and 24 months), while the significant decrease of GAP-43 and alpha-Syn protein was detected at 24 months of age (0.6- and 0.7-fold decrease, respectively). Long-term DR eliminated this decline by increasing GAP-43, SPH and alpha-Syn protein levels (1.7-, 1.7- and 1.6-fold, respectively) thus reverting protein levels to the values measured in 6-month-old animals. Specific pattern of changes observed in the hippocampus identifies this structure as more vulnerable to the processes of aging and with a more pronounced response to the DR effects. The observed DR-induced stabilization of the levels of three presynaptic proteins indicates the beneficial effect of DR on age-related decline in the capacity for synaptic plasticity. (C) 2009 Elsevier Ltd. All rights reserved.
T2  - Neurochemistry International
T1  - Long-term dietary restriction modulates the level of presynaptic proteins in the cortex and hippocampus of the aging rat
IS  - 2
VL  - 56
EP  - 255
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1414
ER  - 

@article{
author = "Mladenović, Aleksandra and Perović, Milka and Tesić, Vesna T and Tanić, Nikola T and Rakić, Ljubisav and Ruždijić, Sabera and Kanazir, Selma",
year = "2010",
abstract = "Brain aging is related to the numerous structural and functional changes including decreased synaptic plasticity. The beneficial effects of dietary restriction (DR) are well known but insufficiently investigated at the level of plasticity-related markers. Therefore, the aim of this study was to examine the expression profiles of proteins structurally and functionally related to synapses-growth-associated protein 43 (GAP-43), synaptophysin (SPH) and alpha-synuclein (alpha-Syn), in the course of aging and in response to long-term DR. The mRNA and protein levels of three presynaptic proteins were assessed by Real Time RT-PCR and Western blotting in the cortex and hippocampus of young (6-month-old), middle-aged (12-month-old), aged (18-month-old) and old (24-month-old) male Wistar rats fed ad libitum and exposed to DR starting from 6 months of age. We observed that long-term DR modulated age-related transcriptional changes by maintaining stable mRNAs levels in the cortex. No major age-related changes of the protein levels were observed in the cortex, while the specific temporal decline was detected in the hippocampus for all three proteins. The SPH levels were decreased across lifespan (0.8-, 0.8- and 0.6-fold change at 12,18 and 24 months), while the significant decrease of GAP-43 and alpha-Syn protein was detected at 24 months of age (0.6- and 0.7-fold decrease, respectively). Long-term DR eliminated this decline by increasing GAP-43, SPH and alpha-Syn protein levels (1.7-, 1.7- and 1.6-fold, respectively) thus reverting protein levels to the values measured in 6-month-old animals. Specific pattern of changes observed in the hippocampus identifies this structure as more vulnerable to the processes of aging and with a more pronounced response to the DR effects. The observed DR-induced stabilization of the levels of three presynaptic proteins indicates the beneficial effect of DR on age-related decline in the capacity for synaptic plasticity. (C) 2009 Elsevier Ltd. All rights reserved.",
journal = "Neurochemistry International",
title = "Long-term dietary restriction modulates the level of presynaptic proteins in the cortex and hippocampus of the aging rat",
number = "2",
volume = "56",
pages = "255",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1414"
}

Mladenović, A., Perović, M., Tesić, V. T., Tanić, N. T., Rakić, L., Ruždijić, S.,& Kanazir, S.. (2010). Long-term dietary restriction modulates the level of presynaptic proteins in the cortex and hippocampus of the aging rat. in Neurochemistry International, 56(2).
https://hdl.handle.net/21.15107/rcub_ibiss_1414

Mladenović A, Perović M, Tesić VT, Tanić NT, Rakić L, Ruždijić S, Kanazir S. Long-term dietary restriction modulates the level of presynaptic proteins in the cortex and hippocampus of the aging rat. in Neurochemistry International. 2010;56(2):null-255.
https://hdl.handle.net/21.15107/rcub_ibiss_1414 .

Mladenović, Aleksandra, Perović, Milka, Tesić, Vesna T, Tanić, Nikola T, Rakić, Ljubisav, Ruždijić, Sabera, Kanazir, Selma, "Long-term dietary restriction modulates the level of presynaptic proteins in the cortex and hippocampus of the aging rat" in Neurochemistry International, 56, no. 2 (2010),
https://hdl.handle.net/21.15107/rcub_ibiss_1414 .

TY  - JOUR
AU  - Smiljanić, Kosara
AU  - Lavrnja, Irena
AU  - Mladenović, Aleksandra
AU  - Ruždijić, Sabera
AU  - Stojiljković, Mirjana B
AU  - Peković, Sanja
AU  - Kanazir, Selma
PY  - 2010
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1357
AB  - Maintaining the cholesterol homeostasis is essential for normal CNS functioning. The enzyme responsible for elimination of cholesterol excess from the brain is cholesterol 24-hydroxylase (Cyp46). Since cholesterol homeostasis is disrupted following brain injury, in this study we examined the effect of right sensorimotor cortex suction ablation on cellular and temporal pattern of Cyp46 expression in the rat brain. Increased expression of Cyp46 at the lesion site at all post injury time points (2, 7, 14, 28 and 45 days post injury, dpi) was detected. Double immunofluorescence staining revealed colocalization of Cyp46 expression with different types of glial cells in time-dependent manner. In ED1(+) microglia/macrophages Cyp46 expression was most prominent at 2 and 7 dpi, whereas Cyp46 immunoreactivity persisted in reactive astrocytes throughout all time points post-injury. However, during the first 2 weeks Cyp46 expression was enhanced in both GFAP(+) and Vim(+) astrocytes, while at 28 and 45 dpi its expression was mostly associated with GFAP(+) cells. Pattern of neuronal Cyp46 expression remained unchanged after the lesion, i.e. Cyp46 immunostaining was detected in dendrites and cell body, but not in axons. The results of this study clearly demonstrate that in pathological conditions, like brain injury, Cyp46 displayed atypical expression, being expressed not only in neuronal cells, but also in microglia and astrocytes. Therefore, injury-induced expression of Cyp46 in microglial and astroglial cells may be involved in the post-injury removal of damaged cell membranes contributing to re-establishment of the brain cholesterol homeostasis.
T2  - Histochemistry and Cell Biology
T1  - Brain injury induces cholesterol 24-hydroxylase (Cyp46) expression in glial cells in a time-dependent manner
IS  - 2
VL  - 134
EP  - 169
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1357
ER  - 

@article{
author = "Smiljanić, Kosara and Lavrnja, Irena and Mladenović, Aleksandra and Ruždijić, Sabera and Stojiljković, Mirjana B and Peković, Sanja and Kanazir, Selma",
year = "2010",
abstract = "Maintaining the cholesterol homeostasis is essential for normal CNS functioning. The enzyme responsible for elimination of cholesterol excess from the brain is cholesterol 24-hydroxylase (Cyp46). Since cholesterol homeostasis is disrupted following brain injury, in this study we examined the effect of right sensorimotor cortex suction ablation on cellular and temporal pattern of Cyp46 expression in the rat brain. Increased expression of Cyp46 at the lesion site at all post injury time points (2, 7, 14, 28 and 45 days post injury, dpi) was detected. Double immunofluorescence staining revealed colocalization of Cyp46 expression with different types of glial cells in time-dependent manner. In ED1(+) microglia/macrophages Cyp46 expression was most prominent at 2 and 7 dpi, whereas Cyp46 immunoreactivity persisted in reactive astrocytes throughout all time points post-injury. However, during the first 2 weeks Cyp46 expression was enhanced in both GFAP(+) and Vim(+) astrocytes, while at 28 and 45 dpi its expression was mostly associated with GFAP(+) cells. Pattern of neuronal Cyp46 expression remained unchanged after the lesion, i.e. Cyp46 immunostaining was detected in dendrites and cell body, but not in axons. The results of this study clearly demonstrate that in pathological conditions, like brain injury, Cyp46 displayed atypical expression, being expressed not only in neuronal cells, but also in microglia and astrocytes. Therefore, injury-induced expression of Cyp46 in microglial and astroglial cells may be involved in the post-injury removal of damaged cell membranes contributing to re-establishment of the brain cholesterol homeostasis.",
journal = "Histochemistry and Cell Biology",
title = "Brain injury induces cholesterol 24-hydroxylase (Cyp46) expression in glial cells in a time-dependent manner",
number = "2",
volume = "134",
pages = "169",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1357"
}

Smiljanić, K., Lavrnja, I., Mladenović, A., Ruždijić, S., Stojiljković, M. B., Peković, S.,& Kanazir, S.. (2010). Brain injury induces cholesterol 24-hydroxylase (Cyp46) expression in glial cells in a time-dependent manner. in Histochemistry and Cell Biology, 134(2).
https://hdl.handle.net/21.15107/rcub_ibiss_1357

Smiljanić K, Lavrnja I, Mladenović A, Ruždijić S, Stojiljković MB, Peković S, Kanazir S. Brain injury induces cholesterol 24-hydroxylase (Cyp46) expression in glial cells in a time-dependent manner. in Histochemistry and Cell Biology. 2010;134(2):null-169.
https://hdl.handle.net/21.15107/rcub_ibiss_1357 .

Smiljanić, Kosara, Lavrnja, Irena, Mladenović, Aleksandra, Ruždijić, Sabera, Stojiljković, Mirjana B, Peković, Sanja, Kanazir, Selma, "Brain injury induces cholesterol 24-hydroxylase (Cyp46) expression in glial cells in a time-dependent manner" in Histochemistry and Cell Biology, 134, no. 2 (2010),
https://hdl.handle.net/21.15107/rcub_ibiss_1357 .

TY  - JOUR
AU  - Vuletić, Ana
AU  - Konjević, Gordana
AU  - Milanović, Desanka
AU  - Ruždijić, Sabera
AU  - Jurisić, Vladimir
PY  - 2010
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1350
AB  - Retinoic acid (RA), similar to specific growth factors, can induce differentiation of proliferating promyelocytic precursors into terminally differentiated granulocytes, although little is known about effects of its 13-cis isomer on promyelocytic leukemia (PML). In this study we demonstrate that 13-cis-RA has a dose and time-dependant antiproliferative effect on HL-60 PML cell line, that it induces cell accumulation in resting G0/G1 phase of the cell cycle followed by an increase in CD11b granulocyte differentiation antigen expression. The obtained increase in the percentage of HL-60 cells in G0/G1 phase and complementary decrease in S phase of the cell cycle are accompanied by a decrease in the expression of cell cycle regulatory molecule cyclin B1. We also show the induction of interferon regulatory factor-I (IRF- I) transcription that can, also, to some extent contribute to the antiproliferative effect of l 3-cis-RA. Furthermore, down-regulation of BcI-2 protein expression in I 3-cis-RA treated HL-60 cells may contribute to sensitivity to apoptosis of growth arrested HL-60 promyelocytic cells.
T2  - Pathology & Oncology Research
T1  - Antiproliferative Effect of 13-cis-Retinoic Acid is Associated with Granulocyte Differentiation and Decrease in Cyclin B1 and Bcl-2 Protein Levels in G0/G1 Arrested HL-60 Cells
IS  - 3
VL  - 16
DO  - 10.1007/s12253-009-9241-2
SP  - 393
EP  - 401
ER  - 

@article{
author = "Vuletić, Ana and Konjević, Gordana and Milanović, Desanka and Ruždijić, Sabera and Jurisić, Vladimir",
year = "2010",
abstract = "Retinoic acid (RA), similar to specific growth factors, can induce differentiation of proliferating promyelocytic precursors into terminally differentiated granulocytes, although little is known about effects of its 13-cis isomer on promyelocytic leukemia (PML). In this study we demonstrate that 13-cis-RA has a dose and time-dependant antiproliferative effect on HL-60 PML cell line, that it induces cell accumulation in resting G0/G1 phase of the cell cycle followed by an increase in CD11b granulocyte differentiation antigen expression. The obtained increase in the percentage of HL-60 cells in G0/G1 phase and complementary decrease in S phase of the cell cycle are accompanied by a decrease in the expression of cell cycle regulatory molecule cyclin B1. We also show the induction of interferon regulatory factor-I (IRF- I) transcription that can, also, to some extent contribute to the antiproliferative effect of l 3-cis-RA. Furthermore, down-regulation of BcI-2 protein expression in I 3-cis-RA treated HL-60 cells may contribute to sensitivity to apoptosis of growth arrested HL-60 promyelocytic cells.",
journal = "Pathology & Oncology Research",
title = "Antiproliferative Effect of 13-cis-Retinoic Acid is Associated with Granulocyte Differentiation and Decrease in Cyclin B1 and Bcl-2 Protein Levels in G0/G1 Arrested HL-60 Cells",
number = "3",
volume = "16",
doi = "10.1007/s12253-009-9241-2",
pages = "393-401"
}

Vuletić, A., Konjević, G., Milanović, D., Ruždijić, S.,& Jurisić, V.. (2010). Antiproliferative Effect of 13-cis-Retinoic Acid is Associated with Granulocyte Differentiation and Decrease in Cyclin B1 and Bcl-2 Protein Levels in G0/G1 Arrested HL-60 Cells. in Pathology & Oncology Research, 16(3), 393-401.
https://doi.org/10.1007/s12253-009-9241-2

Vuletić A, Konjević G, Milanović D, Ruždijić S, Jurisić V. Antiproliferative Effect of 13-cis-Retinoic Acid is Associated with Granulocyte Differentiation and Decrease in Cyclin B1 and Bcl-2 Protein Levels in G0/G1 Arrested HL-60 Cells. in Pathology & Oncology Research. 2010;16(3):393-401.
doi:10.1007/s12253-009-9241-2 .

Vuletić, Ana, Konjević, Gordana, Milanović, Desanka, Ruždijić, Sabera, Jurisić, Vladimir, "Antiproliferative Effect of 13-cis-Retinoic Acid is Associated with Granulocyte Differentiation and Decrease in Cyclin B1 and Bcl-2 Protein Levels in G0/G1 Arrested HL-60 Cells" in Pathology & Oncology Research, 16, no. 3 (2010):393-401,
https://doi.org/10.1007/s12253-009-9241-2 . .

TY  - JOUR
AU  - Pešić, Vesna
AU  - Marinković, Petar
AU  - Petković, Branka
AU  - Ignjatović, Svetlana
AU  - Popić, Jelena
AU  - Kanazir, Selma
AU  - Ruždijić, Sabera
PY  - 2010
UR  - https://www.sciencedirect.com/science/article/abs/pii/S0031938410002908?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3798
AB  - Food restriction (FR) has a beneficial effect on aging process and exerts a significant effect on the responses of rodents to standard behavioral tasks The aim of this study was to assess the cumulative influence of FR on the behavioral and biochemical parameters in Wistar rats Six month-old rats were subjected to restrictive feeding (50% of the daily food intake every-other-day feeding regimen) for one month or for six months until ages of 7 and 12 months respectively We examined the habituation of exploratory movement amphetamine (AMPH)-induced motor activity as well as changes in serum corticosterone (CORT) and glucose levels The results obtained from FR animals were compared with ad libitum (AL)-fed age-matched control rats Habituation of motor activity was only affected by six months of restrictive feeding The sensitization of the motor response to AMPH that was observed in animals exposed to FR for one month was not observed in animals that were exposed to the same feeding regimen for six months Serum CORT was increased and serum glucose was decreased in both FR groups These results clearly show that despite the similarity of the biochemical changes that were Induced by one and six months of FR the nature of the changes in motor activities in these two groups of animals during habituation and after AMPH treatment was different Our findings indicate that long term FR has complex behavioral consequences that need to be carefully evaluated with respect to animal age duration of FR and severity of the diet.
PB  - Pergamon-Elsevier Science Ltd
T2  - Physiology and Behavior
T1  - Changes of behavioral parameters during long-term food restriction in middle-aged Wistar rats
IS  - 5
VL  - 101
DO  - 10.1016/j.physbeh.2010.08.005
SP  - 672
EP  - 678
ER  - 

@article{
author = "Pešić, Vesna and Marinković, Petar and Petković, Branka and Ignjatović, Svetlana and Popić, Jelena and Kanazir, Selma and Ruždijić, Sabera",
year = "2010",
abstract = "Food restriction (FR) has a beneficial effect on aging process and exerts a significant effect on the responses of rodents to standard behavioral tasks The aim of this study was to assess the cumulative influence of FR on the behavioral and biochemical parameters in Wistar rats Six month-old rats were subjected to restrictive feeding (50% of the daily food intake every-other-day feeding regimen) for one month or for six months until ages of 7 and 12 months respectively We examined the habituation of exploratory movement amphetamine (AMPH)-induced motor activity as well as changes in serum corticosterone (CORT) and glucose levels The results obtained from FR animals were compared with ad libitum (AL)-fed age-matched control rats Habituation of motor activity was only affected by six months of restrictive feeding The sensitization of the motor response to AMPH that was observed in animals exposed to FR for one month was not observed in animals that were exposed to the same feeding regimen for six months Serum CORT was increased and serum glucose was decreased in both FR groups These results clearly show that despite the similarity of the biochemical changes that were Induced by one and six months of FR the nature of the changes in motor activities in these two groups of animals during habituation and after AMPH treatment was different Our findings indicate that long term FR has complex behavioral consequences that need to be carefully evaluated with respect to animal age duration of FR and severity of the diet.",
publisher = "Pergamon-Elsevier Science Ltd",
journal = "Physiology and Behavior",
title = "Changes of behavioral parameters during long-term food restriction in middle-aged Wistar rats",
number = "5",
volume = "101",
doi = "10.1016/j.physbeh.2010.08.005",
pages = "672-678"
}

Pešić, V., Marinković, P., Petković, B., Ignjatović, S., Popić, J., Kanazir, S.,& Ruždijić, S.. (2010). Changes of behavioral parameters during long-term food restriction in middle-aged Wistar rats. in Physiology and Behavior
Pergamon-Elsevier Science Ltd., 101(5), 672-678.
https://doi.org/10.1016/j.physbeh.2010.08.005

Pešić V, Marinković P, Petković B, Ignjatović S, Popić J, Kanazir S, Ruždijić S. Changes of behavioral parameters during long-term food restriction in middle-aged Wistar rats. in Physiology and Behavior. 2010;101(5):672-678.
doi:10.1016/j.physbeh.2010.08.005 .

Pešić, Vesna, Marinković, Petar, Petković, Branka, Ignjatović, Svetlana, Popić, Jelena, Kanazir, Selma, Ruždijić, Sabera, "Changes of behavioral parameters during long-term food restriction in middle-aged Wistar rats" in Physiology and Behavior, 101, no. 5 (2010):672-678,
https://doi.org/10.1016/j.physbeh.2010.08.005 . .

TY  - JOUR
AU  - Popović, Natasa M
AU  - Ruždijić, Sabera
AU  - Kanazir, Dusan T.
AU  - Niciforović, Ana
AU  - Adžić, Miroslav
AU  - Paraskevopoulou, Elissavet
AU  - Pantelidou, Constantia
AU  - Radojcić, Marija B
AU  - Demonacos, Constantinos
AU  - Krstić-Demonacos, Marija
PY  - 2010
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1375
AB  - The glucocorticoid receptor (GR) signal transduction and transcriptional regulation are efficiently recapitulated when GR is expressed in Saccharomyces cerevisiae. In this report we demonstrate that the in vivo GR phosphorylation pattern, hormone dependency and interdependency of phosphorylation events were similar in yeast and mammalian cells. GR phosphorylation at S246 exhibited inhibitory effect on S224 and S232 phosphorylation, suggesting the conservation of molecular mechanisms that control this interdependence between yeast and mammalian cells. To assess the effects of GR phosphorylation the mutated GR derivatives T171A, S224A, S232A, S246A were overexpressed and their transcriptional activity was analysed. These receptor derivatives displayed significant hormone inducible transcription when overexpressed in S. cerevisiae. We have established an inducible methionine expression system, which allows the close regulation of the receptor protein levels to analyse the dependence of GR function on its phosphorylation and protein abundance. Using this system we observed that GR S246A mutation increased its activity across all of the GR concentrations tested. The activity of the S224A and S246A mutants was mostly independent of GR protein levels, whereas the WT, T171A and S232A mediated transcription diminished with declining GR protein levels. Our results suggest that GR phosphorylation at specific residues affects its transcriptional functions in a site selective manner and these effects were directly linked to GR dosage. Crown Copyright (C) 2010 Published by Elsevier Inc. All rights reserved.
T2  - Steroids
T1  - Site-specific and dose-dependent effects of glucocorticoid receptor phosphorylation in yeast Saccharomyces cerevisiae
IS  - 6
VL  - 75
EP  - 465
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1375
ER  - 

@article{
author = "Popović, Natasa M and Ruždijić, Sabera and Kanazir, Dusan T. and Niciforović, Ana and Adžić, Miroslav and Paraskevopoulou, Elissavet and Pantelidou, Constantia and Radojcić, Marija B and Demonacos, Constantinos and Krstić-Demonacos, Marija",
year = "2010",
abstract = "The glucocorticoid receptor (GR) signal transduction and transcriptional regulation are efficiently recapitulated when GR is expressed in Saccharomyces cerevisiae. In this report we demonstrate that the in vivo GR phosphorylation pattern, hormone dependency and interdependency of phosphorylation events were similar in yeast and mammalian cells. GR phosphorylation at S246 exhibited inhibitory effect on S224 and S232 phosphorylation, suggesting the conservation of molecular mechanisms that control this interdependence between yeast and mammalian cells. To assess the effects of GR phosphorylation the mutated GR derivatives T171A, S224A, S232A, S246A were overexpressed and their transcriptional activity was analysed. These receptor derivatives displayed significant hormone inducible transcription when overexpressed in S. cerevisiae. We have established an inducible methionine expression system, which allows the close regulation of the receptor protein levels to analyse the dependence of GR function on its phosphorylation and protein abundance. Using this system we observed that GR S246A mutation increased its activity across all of the GR concentrations tested. The activity of the S224A and S246A mutants was mostly independent of GR protein levels, whereas the WT, T171A and S232A mediated transcription diminished with declining GR protein levels. Our results suggest that GR phosphorylation at specific residues affects its transcriptional functions in a site selective manner and these effects were directly linked to GR dosage. Crown Copyright (C) 2010 Published by Elsevier Inc. All rights reserved.",
journal = "Steroids",
title = "Site-specific and dose-dependent effects of glucocorticoid receptor phosphorylation in yeast Saccharomyces cerevisiae",
number = "6",
volume = "75",
pages = "465",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1375"
}

Popović, N. M., Ruždijić, S., Kanazir, D. T., Niciforović, A., Adžić, M., Paraskevopoulou, E., Pantelidou, C., Radojcić, M. B., Demonacos, C.,& Krstić-Demonacos, M.. (2010). Site-specific and dose-dependent effects of glucocorticoid receptor phosphorylation in yeast Saccharomyces cerevisiae. in Steroids, 75(6).
https://hdl.handle.net/21.15107/rcub_ibiss_1375

Popović NM, Ruždijić S, Kanazir DT, Niciforović A, Adžić M, Paraskevopoulou E, Pantelidou C, Radojcić MB, Demonacos C, Krstić-Demonacos M. Site-specific and dose-dependent effects of glucocorticoid receptor phosphorylation in yeast Saccharomyces cerevisiae. in Steroids. 2010;75(6):null-465.
https://hdl.handle.net/21.15107/rcub_ibiss_1375 .

Popović, Natasa M, Ruždijić, Sabera, Kanazir, Dusan T., Niciforović, Ana, Adžić, Miroslav, Paraskevopoulou, Elissavet, Pantelidou, Constantia, Radojcić, Marija B, Demonacos, Constantinos, Krstić-Demonacos, Marija, "Site-specific and dose-dependent effects of glucocorticoid receptor phosphorylation in yeast Saccharomyces cerevisiae" in Steroids, 75, no. 6 (2010),
https://hdl.handle.net/21.15107/rcub_ibiss_1375 .