Zakić, Tamara

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  • Zakić, Tamara (10)

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Breast Cancer: Mitochondria-Centered Metabolic Alterations in Tumor and Associated Adipose Tissue

Zakić, Tamara; Kalezić, Anđelika; Drvendžija, Zorka; Udicki, Mirjana; Ivković Kapicl, Tatjana; Srdić Galić, Biljana; Korać, Aleksandra; Janković, Aleksandra; Korać, Bato

(Basel: MDPI, 2024)

TY  - JOUR
AU  - Zakić, Tamara
AU  - Kalezić, Anđelika
AU  - Drvendžija, Zorka
AU  - Udicki, Mirjana
AU  - Ivković Kapicl, Tatjana
AU  - Srdić Galić, Biljana
AU  - Korać, Aleksandra
AU  - Janković, Aleksandra
AU  - Korać, Bato
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6528
AB  - The close cooperation between breast cancer and cancer-associated adipose tissue (CAAT) shapes the malignant phenotype, but the role of mitochondrial metabolic reprogramming and obesity in breast cancer remains undecided, especially in premenopausal women. Here, we examined mitochondrial metabolic dynamics in paired biopsies of malignant versus benign breast tumor tissue and CAAT in normal-weight and overweight/obese premenopausal women. Lower protein level of pyruvate dehydrogenase and citrate synthase in malignant tumor tissue indicated decreased carbon flux from glucose into the Krebs cycle, whereas the trend was just the opposite in malignant CAAT. Simultaneously, stimulated lipolysis in CAAT of obese women was followed by upregulated β-oxidation, as well as fatty acid synthesis enzymes in both tumor tissue and CAAT of women with malignant tumors, corroborating their physical association. Further, protein level of electron transport chain complexes was generally increased in tumor tissue and CAAT from women with malignant tumors, respective to obesity. Preserved mitochondrial structure in malignant tumor tissue was also observed. However, mitochondrial DNA copy number and protein levels of PGC-1α were dependent on both malignancy and obesity in tumor tissue and CAAT. In conclusion, metabolic cooperation between breast cancer and CAAT in premenopausal women involves obesity-related, synchronized changes in mitochondrial metabolism.
PB  - Basel: MDPI
T2  - Cells
T1  - Breast Cancer: Mitochondria-Centered Metabolic Alterations in Tumor and Associated Adipose Tissue
IS  - 2
VL  - 13
DO  - 10.3390/cells13020155
SP  - 155
ER  - 
@article{
author = "Zakić, Tamara and Kalezić, Anđelika and Drvendžija, Zorka and Udicki, Mirjana and Ivković Kapicl, Tatjana and Srdić Galić, Biljana and Korać, Aleksandra and Janković, Aleksandra and Korać, Bato",
year = "2024",
abstract = "The close cooperation between breast cancer and cancer-associated adipose tissue (CAAT) shapes the malignant phenotype, but the role of mitochondrial metabolic reprogramming and obesity in breast cancer remains undecided, especially in premenopausal women. Here, we examined mitochondrial metabolic dynamics in paired biopsies of malignant versus benign breast tumor tissue and CAAT in normal-weight and overweight/obese premenopausal women. Lower protein level of pyruvate dehydrogenase and citrate synthase in malignant tumor tissue indicated decreased carbon flux from glucose into the Krebs cycle, whereas the trend was just the opposite in malignant CAAT. Simultaneously, stimulated lipolysis in CAAT of obese women was followed by upregulated β-oxidation, as well as fatty acid synthesis enzymes in both tumor tissue and CAAT of women with malignant tumors, corroborating their physical association. Further, protein level of electron transport chain complexes was generally increased in tumor tissue and CAAT from women with malignant tumors, respective to obesity. Preserved mitochondrial structure in malignant tumor tissue was also observed. However, mitochondrial DNA copy number and protein levels of PGC-1α were dependent on both malignancy and obesity in tumor tissue and CAAT. In conclusion, metabolic cooperation between breast cancer and CAAT in premenopausal women involves obesity-related, synchronized changes in mitochondrial metabolism.",
publisher = "Basel: MDPI",
journal = "Cells",
title = "Breast Cancer: Mitochondria-Centered Metabolic Alterations in Tumor and Associated Adipose Tissue",
number = "2",
volume = "13",
doi = "10.3390/cells13020155",
pages = "155"
}
Zakić, T., Kalezić, A., Drvendžija, Z., Udicki, M., Ivković Kapicl, T., Srdić Galić, B., Korać, A., Janković, A.,& Korać, B.. (2024). Breast Cancer: Mitochondria-Centered Metabolic Alterations in Tumor and Associated Adipose Tissue. in Cells
Basel: MDPI., 13(2), 155.
https://doi.org/10.3390/cells13020155
Zakić T, Kalezić A, Drvendžija Z, Udicki M, Ivković Kapicl T, Srdić Galić B, Korać A, Janković A, Korać B. Breast Cancer: Mitochondria-Centered Metabolic Alterations in Tumor and Associated Adipose Tissue. in Cells. 2024;13(2):155.
doi:10.3390/cells13020155 .
Zakić, Tamara, Kalezić, Anđelika, Drvendžija, Zorka, Udicki, Mirjana, Ivković Kapicl, Tatjana, Srdić Galić, Biljana, Korać, Aleksandra, Janković, Aleksandra, Korać, Bato, "Breast Cancer: Mitochondria-Centered Metabolic Alterations in Tumor and Associated Adipose Tissue" in Cells, 13, no. 2 (2024):155,
https://doi.org/10.3390/cells13020155 . .

The discrepancy between morphological and functional activation of brown adipose tissue in the absence of functional Nrf2

Zakić, Tamara; Budnar-Šoškić, Marta; Stojanović, Sara; Janković, Aleksandra; Korać, Aleksandra; Peković-Vaughan, Vanja; Korać, Bato

(Elsevier, 2023)

TY  - CONF
AU  - Zakić, Tamara
AU  - Budnar-Šoškić, Marta
AU  - Stojanović, Sara
AU  - Janković, Aleksandra
AU  - Korać, Aleksandra
AU  - Peković-Vaughan, Vanja
AU  - Korać, Bato
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6527
AB  - The precise regulatory mechanisms of interscapular brown adipose tissue (IBAT) thermogenesis are not fully elucidated, especially those in relation to Nuclear factor erythroid 2–related factor 2 (Nrf2). We have recently shown that mice lacking functional Nrf2 (Nrf2KO) at room temperature (RT) depict thermogenic IBAT activity at the structural level. However, gene and protein expression of the main IBAT thermogenic marker uncoupling protein 1 (UCP1), and other redox-metabolic functional parameters, did not align with this apparent thermogenic activation. Here, we investigated the functional activation of IBAT in wild-type (WT) and Nrf2KO mice maintained at RT (24±1°C) or after cold acclimation (45 days, 4±1°C). We performed immunogold labelling of Nrf2 and its closely related transcription factors Nrf1, Nrf3, and nuclear respiratory factor 1 (NRF1) to determine their spatial expression patterns. Next, we measured succinate-based mitochondrial respiration as an indicator of IBAT mitochondrial oxidative function and uncoupling capacity. Electron microscopy confirmed that Nrf2KO mice at RT had the same ultrastructural characteristics as cold-exposed mice, indicating IBAT thermogenic activity. This was associated with increased mitochondrial immunogold reaction of the above redox-sensitive transcription factors indicating their activation in Nrf2KO mice at RT. In contrast to such activated phenotype, respirometry results showed that Nrf2KO mice at RT had no uncoupling activity compared to cold-exposed WT mice. Furthermore, similar respiratory pattern was observed in Nrf2KO mice acclimated to cold, regardless of increased UCP1 expression. These results demonstrate that despite the (ultra)structural recruitment of IBAT in Nrf2KO mice at RT and after cold acclimation, Nrf2 is essential for the full functional thermogenic activation of IBAT and the lack of functional Nrf2 could not be compensated with Nrf1, Nrf3, and NRF1.
PB  - Elsevier
C3  - Redox Biology Congress 2023; 2023 Jun 6-9; Vienna, Austria
T1  - The discrepancy between morphological and functional activation of brown adipose tissue in the absence of functional Nrf2
DO  - 10.1016/j.freeradbiomed.2023.03.109
SP  - 25
ER  - 
@conference{
author = "Zakić, Tamara and Budnar-Šoškić, Marta and Stojanović, Sara and Janković, Aleksandra and Korać, Aleksandra and Peković-Vaughan, Vanja and Korać, Bato",
year = "2023",
abstract = "The precise regulatory mechanisms of interscapular brown adipose tissue (IBAT) thermogenesis are not fully elucidated, especially those in relation to Nuclear factor erythroid 2–related factor 2 (Nrf2). We have recently shown that mice lacking functional Nrf2 (Nrf2KO) at room temperature (RT) depict thermogenic IBAT activity at the structural level. However, gene and protein expression of the main IBAT thermogenic marker uncoupling protein 1 (UCP1), and other redox-metabolic functional parameters, did not align with this apparent thermogenic activation. Here, we investigated the functional activation of IBAT in wild-type (WT) and Nrf2KO mice maintained at RT (24±1°C) or after cold acclimation (45 days, 4±1°C). We performed immunogold labelling of Nrf2 and its closely related transcription factors Nrf1, Nrf3, and nuclear respiratory factor 1 (NRF1) to determine their spatial expression patterns. Next, we measured succinate-based mitochondrial respiration as an indicator of IBAT mitochondrial oxidative function and uncoupling capacity. Electron microscopy confirmed that Nrf2KO mice at RT had the same ultrastructural characteristics as cold-exposed mice, indicating IBAT thermogenic activity. This was associated with increased mitochondrial immunogold reaction of the above redox-sensitive transcription factors indicating their activation in Nrf2KO mice at RT. In contrast to such activated phenotype, respirometry results showed that Nrf2KO mice at RT had no uncoupling activity compared to cold-exposed WT mice. Furthermore, similar respiratory pattern was observed in Nrf2KO mice acclimated to cold, regardless of increased UCP1 expression. These results demonstrate that despite the (ultra)structural recruitment of IBAT in Nrf2KO mice at RT and after cold acclimation, Nrf2 is essential for the full functional thermogenic activation of IBAT and the lack of functional Nrf2 could not be compensated with Nrf1, Nrf3, and NRF1.",
publisher = "Elsevier",
journal = "Redox Biology Congress 2023; 2023 Jun 6-9; Vienna, Austria",
title = "The discrepancy between morphological and functional activation of brown adipose tissue in the absence of functional Nrf2",
doi = "10.1016/j.freeradbiomed.2023.03.109",
pages = "25"
}
Zakić, T., Budnar-Šoškić, M., Stojanović, S., Janković, A., Korać, A., Peković-Vaughan, V.,& Korać, B.. (2023). The discrepancy between morphological and functional activation of brown adipose tissue in the absence of functional Nrf2. in Redox Biology Congress 2023; 2023 Jun 6-9; Vienna, Austria
Elsevier., 25.
https://doi.org/10.1016/j.freeradbiomed.2023.03.109
Zakić T, Budnar-Šoškić M, Stojanović S, Janković A, Korać A, Peković-Vaughan V, Korać B. The discrepancy between morphological and functional activation of brown adipose tissue in the absence of functional Nrf2. in Redox Biology Congress 2023; 2023 Jun 6-9; Vienna, Austria. 2023;:25.
doi:10.1016/j.freeradbiomed.2023.03.109 .
Zakić, Tamara, Budnar-Šoškić, Marta, Stojanović, Sara, Janković, Aleksandra, Korać, Aleksandra, Peković-Vaughan, Vanja, Korać, Bato, "The discrepancy between morphological and functional activation of brown adipose tissue in the absence of functional Nrf2" in Redox Biology Congress 2023; 2023 Jun 6-9; Vienna, Austria (2023):25,
https://doi.org/10.1016/j.freeradbiomed.2023.03.109 . .

Nrf2 coordinates redox-metabolic homeostasis required for lipid deposition in rat visceral adipose tissue during the re-acclimation of rats after cold

Budnar Šoškić, Marta; Zakić, Tamara; Korać, Aleksandra; Korać, Bato; Janković, Aleksandra

(Elsevier, 2023)

TY  - CONF
AU  - Budnar Šoškić, Marta
AU  - Zakić, Tamara
AU  - Korać, Aleksandra
AU  - Korać, Bato
AU  - Janković, Aleksandra
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6526
AB  - Тight control of the lipid-deposition function of white adipose tissue (WAT) defines the overall metabolic homeostasis and entails coordinated antioxidant response. We aimed to reveal temporal changes in the antioxidant defence (AD) that is a prerequisite for lipid metabolism in the visceral WAT over 45 days of re-acclimation to room temperature (RT, 22±1 °C) in rats pre-acclimated to cold (45 days, 4±1 °C). The Nuclear factor erythroid 2–related factor 2 (Nrf2) and its downstream antioxidant targets, as well as key lipogenic enzymes were examined in epididymal WAT (eWAT) and compared to the RT-maintained control. Upregulation of Nrf2 protein expression observed from the 1-12th day of re-acclimation was followed by an increase in the glutathione level (3-7th day) and the protein expression of copper, zinc superoxide dismutase (3-12th day), manganese superoxide dismutase (1-12th day), thioredoxin (1-45th day), and glutathione peroxidase (1-45th day). Such time-dependent changes in AD during re-acclimation coincided with increases in the lipogenic enzymes acetyl-CoA carboxylase and fatty acid synthase that were further supported by elevated glyceraldehyde 3-phosphate dehydrogenase and glucose 6-phosphate dehydrogenase protein levels. Observed redox-metabolic integration in eWAT resulted in the restitution of relative eWAT mass on the 12th day of re-acclimation. It can be concluded that Nrf2-coordinated redox-metabolic changes drive the restitution of eWAT lipid depot during the re-acclimation of rats after cold. These results show a novel role of Nrf2 in regulating redox-metabolic signaling under homeostatic conditions and its relevance in visceral adiposity in different metabolic diseases.
PB  - Elsevier
C3  - Redox Biology Congress 2023; 2023 Jun 6-9; Vienna, Austria
T1  - Nrf2 coordinates redox-metabolic homeostasis required for lipid deposition in rat visceral adipose tissue during the re-acclimation of rats after cold
DO  - 10.1016/j.freeradbiomed.2023.03.183
SP  - 26
ER  - 
@conference{
author = "Budnar Šoškić, Marta and Zakić, Tamara and Korać, Aleksandra and Korać, Bato and Janković, Aleksandra",
year = "2023",
abstract = "Тight control of the lipid-deposition function of white adipose tissue (WAT) defines the overall metabolic homeostasis and entails coordinated antioxidant response. We aimed to reveal temporal changes in the antioxidant defence (AD) that is a prerequisite for lipid metabolism in the visceral WAT over 45 days of re-acclimation to room temperature (RT, 22±1 °C) in rats pre-acclimated to cold (45 days, 4±1 °C). The Nuclear factor erythroid 2–related factor 2 (Nrf2) and its downstream antioxidant targets, as well as key lipogenic enzymes were examined in epididymal WAT (eWAT) and compared to the RT-maintained control. Upregulation of Nrf2 protein expression observed from the 1-12th day of re-acclimation was followed by an increase in the glutathione level (3-7th day) and the protein expression of copper, zinc superoxide dismutase (3-12th day), manganese superoxide dismutase (1-12th day), thioredoxin (1-45th day), and glutathione peroxidase (1-45th day). Such time-dependent changes in AD during re-acclimation coincided with increases in the lipogenic enzymes acetyl-CoA carboxylase and fatty acid synthase that were further supported by elevated glyceraldehyde 3-phosphate dehydrogenase and glucose 6-phosphate dehydrogenase protein levels. Observed redox-metabolic integration in eWAT resulted in the restitution of relative eWAT mass on the 12th day of re-acclimation. It can be concluded that Nrf2-coordinated redox-metabolic changes drive the restitution of eWAT lipid depot during the re-acclimation of rats after cold. These results show a novel role of Nrf2 in regulating redox-metabolic signaling under homeostatic conditions and its relevance in visceral adiposity in different metabolic diseases.",
publisher = "Elsevier",
journal = "Redox Biology Congress 2023; 2023 Jun 6-9; Vienna, Austria",
title = "Nrf2 coordinates redox-metabolic homeostasis required for lipid deposition in rat visceral adipose tissue during the re-acclimation of rats after cold",
doi = "10.1016/j.freeradbiomed.2023.03.183",
pages = "26"
}
Budnar Šoškić, M., Zakić, T., Korać, A., Korać, B.,& Janković, A.. (2023). Nrf2 coordinates redox-metabolic homeostasis required for lipid deposition in rat visceral adipose tissue during the re-acclimation of rats after cold. in Redox Biology Congress 2023; 2023 Jun 6-9; Vienna, Austria
Elsevier., 26.
https://doi.org/10.1016/j.freeradbiomed.2023.03.183
Budnar Šoškić M, Zakić T, Korać A, Korać B, Janković A. Nrf2 coordinates redox-metabolic homeostasis required for lipid deposition in rat visceral adipose tissue during the re-acclimation of rats after cold. in Redox Biology Congress 2023; 2023 Jun 6-9; Vienna, Austria. 2023;:26.
doi:10.1016/j.freeradbiomed.2023.03.183 .
Budnar Šoškić, Marta, Zakić, Tamara, Korać, Aleksandra, Korać, Bato, Janković, Aleksandra, "Nrf2 coordinates redox-metabolic homeostasis required for lipid deposition in rat visceral adipose tissue during the re-acclimation of rats after cold" in Redox Biology Congress 2023; 2023 Jun 6-9; Vienna, Austria (2023):26,
https://doi.org/10.1016/j.freeradbiomed.2023.03.183 . .

Redox and metabolic reprogramming in breast cancer and cancer-associated adipose tissue

Zakić, Tamara; Peković-Vaughan, Vanja; Čvoro, Aleksandra; Korać, Aleksandra; Janković, Aleksandra; Korać, Bato

(John Wiley, 2023)

TY  - JOUR
AU  - Zakić, Tamara
AU  - Peković-Vaughan, Vanja
AU  - Čvoro, Aleksandra
AU  - Korać, Aleksandra
AU  - Janković, Aleksandra
AU  - Korać, Bato
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6519
AB  - Redox and metabolic processes are tightly coupled in both physiological and pathological conditions. In cancer, their integration occurs at multiple levels and is characterized by synchronized reprogramming both in the tumor tissue and its specific but heterogeneous microenvironment. In breast cancer, the principal microenvironment is the cancer-associated adipose tissue (CAAT). Understanding how the redox-metabolic reprogramming becomes coordinated in human breast cancer is imperative both for cancer prevention and for the establishment of new therapeutic approaches. This review aims to provide an overview of the current knowledge of the redox profiles and regulation of intermediary metabolism in breast cancer while considering the tumor and CAAT of breast cancer as a unique Warburg's pseudo-organ. As cancer is now recognized as a systemic metabolic disease, we have paid particular attention to the cell-specific redox-metabolic reprogramming and the roles of estrogen receptors and circadian rhythms, as well as their crosstalk in the development, growth, progression, and prognosis of breast cancer.
PB  - John Wiley
T2  - FEBS Letters
T1  - Redox and metabolic reprogramming in breast cancer and cancer-associated adipose tissue
DO  - 10.1002/1873-3468.14794
ER  - 
@article{
author = "Zakić, Tamara and Peković-Vaughan, Vanja and Čvoro, Aleksandra and Korać, Aleksandra and Janković, Aleksandra and Korać, Bato",
year = "2023",
abstract = "Redox and metabolic processes are tightly coupled in both physiological and pathological conditions. In cancer, their integration occurs at multiple levels and is characterized by synchronized reprogramming both in the tumor tissue and its specific but heterogeneous microenvironment. In breast cancer, the principal microenvironment is the cancer-associated adipose tissue (CAAT). Understanding how the redox-metabolic reprogramming becomes coordinated in human breast cancer is imperative both for cancer prevention and for the establishment of new therapeutic approaches. This review aims to provide an overview of the current knowledge of the redox profiles and regulation of intermediary metabolism in breast cancer while considering the tumor and CAAT of breast cancer as a unique Warburg's pseudo-organ. As cancer is now recognized as a systemic metabolic disease, we have paid particular attention to the cell-specific redox-metabolic reprogramming and the roles of estrogen receptors and circadian rhythms, as well as their crosstalk in the development, growth, progression, and prognosis of breast cancer.",
publisher = "John Wiley",
journal = "FEBS Letters",
title = "Redox and metabolic reprogramming in breast cancer and cancer-associated adipose tissue",
doi = "10.1002/1873-3468.14794"
}
Zakić, T., Peković-Vaughan, V., Čvoro, A., Korać, A., Janković, A.,& Korać, B.. (2023). Redox and metabolic reprogramming in breast cancer and cancer-associated adipose tissue. in FEBS Letters
John Wiley..
https://doi.org/10.1002/1873-3468.14794
Zakić T, Peković-Vaughan V, Čvoro A, Korać A, Janković A, Korać B. Redox and metabolic reprogramming in breast cancer and cancer-associated adipose tissue. in FEBS Letters. 2023;.
doi:10.1002/1873-3468.14794 .
Zakić, Tamara, Peković-Vaughan, Vanja, Čvoro, Aleksandra, Korać, Aleksandra, Janković, Aleksandra, Korać, Bato, "Redox and metabolic reprogramming in breast cancer and cancer-associated adipose tissue" in FEBS Letters (2023),
https://doi.org/10.1002/1873-3468.14794 . .
1
2
1

Redox‐metabolic reprogramming of skin in mice lacking functional Nrf2 under basal conditions and cold acclimation

Zakić, Tamara; Stojanović, Sara; Janković, Aleksandra; Korać, Aleksandra; Peković‐Vaughan, Vanja; Korać, Bato

(2022)

TY  - JOUR
AU  - Zakić, Tamara
AU  - Stojanović, Sara
AU  - Janković, Aleksandra
AU  - Korać, Aleksandra
AU  - Peković‐Vaughan, Vanja
AU  - Korać, Bato
PY  - 2022
UR  - https://onlinelibrary.wiley.com/doi/10.1002/biof.1931
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5385
AB  - Adaptive responses to environmental and physiological challenges, including exposure to low environmental temperature, require extensive structural, redox, and metabolic reprogramming. Detailed molecular mechanisms of such processes in the skin are lacking, especially the role of nuclear factor erythroid 2-related factor 2 (Nrf2) and other closely related redox-sensitive transcription factors Nrf1, Nrf3, and nuclear respiratory factor (NRF1). To investigate the role of Nrf2, we examined redox and metabolic responses in the skin of wild-type (WT) mice and mice lacking functional Nrf2 (Nrf2 KO) at room (RT, 24 ± 1°C) and cold (4 ± 1°C) temperature. Our results demonstrate distinct expression profiles of major enzymes involved in antioxidant defense and key metabolic and mitochondrial pathways in the skin, depending on the functional Nrf2 and/or cold stimulus. Nrf2 KO mice at RT displayed profound alterations in redox, mitochondrial and metabolic responses, generally akin to cold-induced skin responses in WT mice. Immunohistochemical analyses of skin cell compartments (keratinocytes, fibroblasts, hair follicle, and sebaceous gland) and spatial locations (nucleus and cytoplasm) revealed synergistic interactions between members of the Nrf transcription factor family as part of redox-metabolic reprogramming in WT mice upon cold acclimation. In contrast, Nrf2 KO mice at RT showed loss of NRF1 expression and a compensatory activation of Nrf1/Nrf3, which was abolished upon cold, concomitant with blunted redox-metabolic responses. These data show for the first time a novel role for Nrf2 in skin physiology in response to low environmental temperature, with important implications in human connective tissue diseases with altered thermogenic responses.
T2  - BioFactors
T1  - Redox‐metabolic reprogramming of skin in mice lacking functional Nrf2 under basal conditions and cold acclimation
DO  - 10.1002/biof.1931
ER  - 
@article{
author = "Zakić, Tamara and Stojanović, Sara and Janković, Aleksandra and Korać, Aleksandra and Peković‐Vaughan, Vanja and Korać, Bato",
year = "2022",
abstract = "Adaptive responses to environmental and physiological challenges, including exposure to low environmental temperature, require extensive structural, redox, and metabolic reprogramming. Detailed molecular mechanisms of such processes in the skin are lacking, especially the role of nuclear factor erythroid 2-related factor 2 (Nrf2) and other closely related redox-sensitive transcription factors Nrf1, Nrf3, and nuclear respiratory factor (NRF1). To investigate the role of Nrf2, we examined redox and metabolic responses in the skin of wild-type (WT) mice and mice lacking functional Nrf2 (Nrf2 KO) at room (RT, 24 ± 1°C) and cold (4 ± 1°C) temperature. Our results demonstrate distinct expression profiles of major enzymes involved in antioxidant defense and key metabolic and mitochondrial pathways in the skin, depending on the functional Nrf2 and/or cold stimulus. Nrf2 KO mice at RT displayed profound alterations in redox, mitochondrial and metabolic responses, generally akin to cold-induced skin responses in WT mice. Immunohistochemical analyses of skin cell compartments (keratinocytes, fibroblasts, hair follicle, and sebaceous gland) and spatial locations (nucleus and cytoplasm) revealed synergistic interactions between members of the Nrf transcription factor family as part of redox-metabolic reprogramming in WT mice upon cold acclimation. In contrast, Nrf2 KO mice at RT showed loss of NRF1 expression and a compensatory activation of Nrf1/Nrf3, which was abolished upon cold, concomitant with blunted redox-metabolic responses. These data show for the first time a novel role for Nrf2 in skin physiology in response to low environmental temperature, with important implications in human connective tissue diseases with altered thermogenic responses.",
journal = "BioFactors",
title = "Redox‐metabolic reprogramming of skin in mice lacking functional Nrf2 under basal conditions and cold acclimation",
doi = "10.1002/biof.1931"
}
Zakić, T., Stojanović, S., Janković, A., Korać, A., Peković‐Vaughan, V.,& Korać, B.. (2022). Redox‐metabolic reprogramming of skin in mice lacking functional Nrf2 under basal conditions and cold acclimation. in BioFactors.
https://doi.org/10.1002/biof.1931
Zakić T, Stojanović S, Janković A, Korać A, Peković‐Vaughan V, Korać B. Redox‐metabolic reprogramming of skin in mice lacking functional Nrf2 under basal conditions and cold acclimation. in BioFactors. 2022;.
doi:10.1002/biof.1931 .
Zakić, Tamara, Stojanović, Sara, Janković, Aleksandra, Korać, Aleksandra, Peković‐Vaughan, Vanja, Korać, Bato, "Redox‐metabolic reprogramming of skin in mice lacking functional Nrf2 under basal conditions and cold acclimation" in BioFactors (2022),
https://doi.org/10.1002/biof.1931 . .

Structural and redox-metabolic remodelling of brown adipose tissue in mice lacking nuclear factor erythroid 2-related factor 2 under basal conditions and cold acclimation

Zakić, Tamara; Ninković, Anastasija; Stojanović, Sara; Budnar Šoškić, Marta; Kalezić, Anđelika; Janković, Aleksandra; Korać, Aleksandra; Peković-Vaughan, Vanja; Korać, Bato

(Society for Free Radical Research-Europe, 2022)

TY  - CONF
AU  - Zakić, Tamara
AU  - Ninković, Anastasija
AU  - Stojanović, Sara
AU  - Budnar Šoškić, Marta
AU  - Kalezić, Anđelika
AU  - Janković, Aleksandra
AU  - Korać, Aleksandra
AU  - Peković-Vaughan, Vanja
AU  - Korać, Bato
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5128
AB  - Interscapular brown adipose tissue (IBAT) is a highly metabolically active, thermogenic tissue essential for the maintenance of total energy homeostasis, with a remarkable ability for remodelling in response to exogenous stimuli. Given that nuclear factor erythroid 2-related factor 2 (NRF2) has a pivotal role in redox-metabolic homeostasis, we aimed to investigate its role in IBAT homeostasis under basal conditions or upon cold stimulation. Therefore, we analysed structural and redox-metabolic profiles of IBAT in wild-type (WT) and mice lacking functional Nrf2 (Nrf2KO) maintained at room (RT, 24±1°C) or low temperature (4±1°C). Our results show that both WT and Nrf2KO mice appear to be acclimated to cold, showing characteristics of thermogenically active IBAT, including increased gene and protein expression of uncoupling protein 1 (UCP1). Surprisingly, light and electron microscopy revealed that Nrf2KO mice at RT displayed distinct structural features of activated IBAT, together with the presence of vasodilated blood vessels, while the expression of thermogenic marker UCP1 did not show a corresponding cold-induced change, thus indicating IBAT functional inactivity. This lack of IBAT thermogenic activity in Nrf2KO mice at RT is consistent with its altered redox-metabolic profile, whereby protein expression of the main antioxidant defence and key metabolic enzymes either remained the same or was decreased compared to WT mice at RT. Accordingly, circulatory levels of triglycerides and cholesterol were decreased while glucose, urea and creatinine remained unchanged. Moreover, gene and/or protein expression of important redox-metabolic transcriptional factors – erythroid NRF1, NFkB, PGC-1α and PPARγ, as well as eNOS and AMPKα were increased, suggesting compensatory molecular mechanisms leading to altered IBAT phenotype in Nrf2KO mice at RT. In conclusion, the lack of functional Nrf2 leads to marked structural characteristics of active IBAT in Nrf2KO mice at RT, which are only followed by its functional activation through distinct redox-metabolic reprogramming after cold stimulation.
PB  - Society for Free Radical Research-Europe
C3  - Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium
T1  - Structural and redox-metabolic remodelling of brown adipose tissue in mice lacking nuclear factor erythroid 2-related factor 2 under basal conditions and cold acclimation
DO  - 10.1016/j.freeradbiomed.2022.06.035
SP  - 5
ER  - 
@conference{
author = "Zakić, Tamara and Ninković, Anastasija and Stojanović, Sara and Budnar Šoškić, Marta and Kalezić, Anđelika and Janković, Aleksandra and Korać, Aleksandra and Peković-Vaughan, Vanja and Korać, Bato",
year = "2022",
abstract = "Interscapular brown adipose tissue (IBAT) is a highly metabolically active, thermogenic tissue essential for the maintenance of total energy homeostasis, with a remarkable ability for remodelling in response to exogenous stimuli. Given that nuclear factor erythroid 2-related factor 2 (NRF2) has a pivotal role in redox-metabolic homeostasis, we aimed to investigate its role in IBAT homeostasis under basal conditions or upon cold stimulation. Therefore, we analysed structural and redox-metabolic profiles of IBAT in wild-type (WT) and mice lacking functional Nrf2 (Nrf2KO) maintained at room (RT, 24±1°C) or low temperature (4±1°C). Our results show that both WT and Nrf2KO mice appear to be acclimated to cold, showing characteristics of thermogenically active IBAT, including increased gene and protein expression of uncoupling protein 1 (UCP1). Surprisingly, light and electron microscopy revealed that Nrf2KO mice at RT displayed distinct structural features of activated IBAT, together with the presence of vasodilated blood vessels, while the expression of thermogenic marker UCP1 did not show a corresponding cold-induced change, thus indicating IBAT functional inactivity. This lack of IBAT thermogenic activity in Nrf2KO mice at RT is consistent with its altered redox-metabolic profile, whereby protein expression of the main antioxidant defence and key metabolic enzymes either remained the same or was decreased compared to WT mice at RT. Accordingly, circulatory levels of triglycerides and cholesterol were decreased while glucose, urea and creatinine remained unchanged. Moreover, gene and/or protein expression of important redox-metabolic transcriptional factors – erythroid NRF1, NFkB, PGC-1α and PPARγ, as well as eNOS and AMPKα were increased, suggesting compensatory molecular mechanisms leading to altered IBAT phenotype in Nrf2KO mice at RT. In conclusion, the lack of functional Nrf2 leads to marked structural characteristics of active IBAT in Nrf2KO mice at RT, which are only followed by its functional activation through distinct redox-metabolic reprogramming after cold stimulation.",
publisher = "Society for Free Radical Research-Europe",
journal = "Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium",
title = "Structural and redox-metabolic remodelling of brown adipose tissue in mice lacking nuclear factor erythroid 2-related factor 2 under basal conditions and cold acclimation",
doi = "10.1016/j.freeradbiomed.2022.06.035",
pages = "5"
}
Zakić, T., Ninković, A., Stojanović, S., Budnar Šoškić, M., Kalezić, A., Janković, A., Korać, A., Peković-Vaughan, V.,& Korać, B.. (2022). Structural and redox-metabolic remodelling of brown adipose tissue in mice lacking nuclear factor erythroid 2-related factor 2 under basal conditions and cold acclimation. in Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium
Society for Free Radical Research-Europe., 5.
https://doi.org/10.1016/j.freeradbiomed.2022.06.035
Zakić T, Ninković A, Stojanović S, Budnar Šoškić M, Kalezić A, Janković A, Korać A, Peković-Vaughan V, Korać B. Structural and redox-metabolic remodelling of brown adipose tissue in mice lacking nuclear factor erythroid 2-related factor 2 under basal conditions and cold acclimation. in Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium. 2022;:5.
doi:10.1016/j.freeradbiomed.2022.06.035 .
Zakić, Tamara, Ninković, Anastasija, Stojanović, Sara, Budnar Šoškić, Marta, Kalezić, Anđelika, Janković, Aleksandra, Korać, Aleksandra, Peković-Vaughan, Vanja, Korać, Bato, "Structural and redox-metabolic remodelling of brown adipose tissue in mice lacking nuclear factor erythroid 2-related factor 2 under basal conditions and cold acclimation" in Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium (2022):5,
https://doi.org/10.1016/j.freeradbiomed.2022.06.035 . .

UCP1 - a lever of the redox-metabolic seesaw in the regulation of lipid-buffering function of white adipose tissue

Janković, Aleksandra; Kalezić, Anđelika; Zakić, Tamara; Budnar Šoškić, Marta; Korać, Aleksandra

(Society for Free Radical Research-Europe, 2022)

TY  - CONF
AU  - Janković, Aleksandra
AU  - Kalezić, Anđelika
AU  - Zakić, Tamara
AU  - Budnar Šoškić, Marta
AU  - Korać, Aleksandra
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5127
AB  - Uncoupling protein 1 (UCP1) is a molecular hallmark of thermogenic adipocytes. It can also reside in the unilocular adipocytes of white adipose tissue (WAT) that do not possess almost any oxidation and thermogenesis capacity. Therefore, the significance of UCP1 in WAT is vague. To clarify the physiological role of UCP1 in white adipocytes we aimed to investigate the relation of UCP1 expression with the components of redox-adaptive homeostasis and metabolic function in WAT. Toward this, we investigated the expression pattern of UCP1 with Nrf2 and its downstream targets, glutathione (GSH), and lipid peroxidation levels during extensive lipolysis induced by long-term cold exposure and during reversal, when lipid deposits in adipocytes recover, upon re-acclimation from cold to room temperature (RT). To this end, stated molecular targets were investigated at different time points during 45 days of cold acclimation and re-acclimation in the rat retroperitoneal WAT (rpWAT) and compared to respective RT and cold-acclimated controls. The results have shown that in response to cold-induced lipid mobilization transient induction of UCP1 precedes Nrf2 expression and upregulation of downstream antioxidant enzymes (such as MnSOD and GST). The reverse sequence of molecular events was observed during the early (1-12. days) and late (12-45. days) periods of re-acclimation from cold to RT. Namely, in the initial days of re-acclimation high lipogenesis and redox threshold (GSH, and expression of CuZnSOD and MnSOD) correspond to lower UCP1 levels. From the moment of restitution of lipid reserves (revealed by rpWAT mass) and on, UCP1, GSH, and most antioxidant enzymes return to their RT control values. The results emphasize that UCP1 and Nrf2 represent levers of redox-metabolic seesaw fine-tuning of redox homeostasis for optimal regulation of lipid mobilization and deposition in white adipocytes. Research is supported by the Science Fund of the Republic of Serbia, PROMIS, #6066747-WARMED.
PB  - Society for Free Radical Research-Europe
C3  - Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium
T1  - UCP1 - a lever of the redox-metabolic seesaw in the regulation of lipid-buffering function of white adipose tissue
DO  - 10.1016/j.freeradbiomed.2022.06.152
SP  - 35
ER  - 
@conference{
author = "Janković, Aleksandra and Kalezić, Anđelika and Zakić, Tamara and Budnar Šoškić, Marta and Korać, Aleksandra",
year = "2022",
abstract = "Uncoupling protein 1 (UCP1) is a molecular hallmark of thermogenic adipocytes. It can also reside in the unilocular adipocytes of white adipose tissue (WAT) that do not possess almost any oxidation and thermogenesis capacity. Therefore, the significance of UCP1 in WAT is vague. To clarify the physiological role of UCP1 in white adipocytes we aimed to investigate the relation of UCP1 expression with the components of redox-adaptive homeostasis and metabolic function in WAT. Toward this, we investigated the expression pattern of UCP1 with Nrf2 and its downstream targets, glutathione (GSH), and lipid peroxidation levels during extensive lipolysis induced by long-term cold exposure and during reversal, when lipid deposits in adipocytes recover, upon re-acclimation from cold to room temperature (RT). To this end, stated molecular targets were investigated at different time points during 45 days of cold acclimation and re-acclimation in the rat retroperitoneal WAT (rpWAT) and compared to respective RT and cold-acclimated controls. The results have shown that in response to cold-induced lipid mobilization transient induction of UCP1 precedes Nrf2 expression and upregulation of downstream antioxidant enzymes (such as MnSOD and GST). The reverse sequence of molecular events was observed during the early (1-12. days) and late (12-45. days) periods of re-acclimation from cold to RT. Namely, in the initial days of re-acclimation high lipogenesis and redox threshold (GSH, and expression of CuZnSOD and MnSOD) correspond to lower UCP1 levels. From the moment of restitution of lipid reserves (revealed by rpWAT mass) and on, UCP1, GSH, and most antioxidant enzymes return to their RT control values. The results emphasize that UCP1 and Nrf2 represent levers of redox-metabolic seesaw fine-tuning of redox homeostasis for optimal regulation of lipid mobilization and deposition in white adipocytes. Research is supported by the Science Fund of the Republic of Serbia, PROMIS, #6066747-WARMED.",
publisher = "Society for Free Radical Research-Europe",
journal = "Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium",
title = "UCP1 - a lever of the redox-metabolic seesaw in the regulation of lipid-buffering function of white adipose tissue",
doi = "10.1016/j.freeradbiomed.2022.06.152",
pages = "35"
}
Janković, A., Kalezić, A., Zakić, T., Budnar Šoškić, M.,& Korać, A.. (2022). UCP1 - a lever of the redox-metabolic seesaw in the regulation of lipid-buffering function of white adipose tissue. in Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium
Society for Free Radical Research-Europe., 35.
https://doi.org/10.1016/j.freeradbiomed.2022.06.152
Janković A, Kalezić A, Zakić T, Budnar Šoškić M, Korać A. UCP1 - a lever of the redox-metabolic seesaw in the regulation of lipid-buffering function of white adipose tissue. in Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium. 2022;:35.
doi:10.1016/j.freeradbiomed.2022.06.152 .
Janković, Aleksandra, Kalezić, Anđelika, Zakić, Tamara, Budnar Šoškić, Marta, Korać, Aleksandra, "UCP1 - a lever of the redox-metabolic seesaw in the regulation of lipid-buffering function of white adipose tissue" in Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium (2022):35,
https://doi.org/10.1016/j.freeradbiomed.2022.06.152 . .
1

Effects of Remote Ischaemic Preconditioning on the Internal Thoracic Artery Nitric Oxide Synthase Isoforms in Patients Undergoing Coronary Artery Bypass Grafting.

Janković, Aleksandra; Zakić, Tamara; Miličić, Miroslav; Unić-Stojanović, Dragana; Kalezić, Anđelika; Korać, Aleksandra; Jović, Miomir; Korać, Bato

(Basel: MDPI, 2021)

TY  - JOUR
AU  - Janković, Aleksandra
AU  - Zakić, Tamara
AU  - Miličić, Miroslav
AU  - Unić-Stojanović, Dragana
AU  - Kalezić, Anđelika
AU  - Korać, Aleksandra
AU  - Jović, Miomir
AU  - Korać, Bato
PY  - 2021
UR  - https://www.mdpi.com/2076-3921/10/12/1910
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC8750270
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4740
AB  - Remote ischaemic preconditioning (RIPC) is a medical procedure that consists of repeated brief periods of transient ischaemia and reperfusion of distant organs (limbs) with the ability to provide internal organ protection from ischaemia. Even though RIPC has been successfully applied in patients with myocardial infarction during coronary revascularization (surgery/percutaneous angioplasty), the underlying molecular mechanisms are yet to be clarified. Thus, our study aimed to determine the role of nitric oxide synthase (NOS) isoforms in RIPC-induced protection (3 × 5 min of forearm ischaemia with 5 min of reperfusion) of arterial graft in patients undergoing urgent coronary artery bypass grafting (CABG). We examined RIPC effects on specific expression and immunolocalization of three NOS isoforms - endothelial (eNOS), inducible (iNOS) and neuronal (nNOS) in patients' internal thoracic artery (ITA) used as a graft. We found that the application of RIPC protocol leads to an increased protein expression of eNOS, which was further confirmed with strong eNOS immunopositivity, especially in the endothelium and smooth muscle cells of ITA. The same analysis of two other NOS isoforms, iNOS and nNOS, showed no significant differences between patients undergoing CABG with or without RIPC. Our results demonstrate RIPC-induced upregulation of eNOS in human ITA, pointing to its significance in achieving protective phenotype on a systemic level with important implications for graft patency.
PB  - Basel: MDPI
T2  - Antioxidants (Basel, Switzerland)
T1  - Effects of Remote Ischaemic Preconditioning on the Internal Thoracic Artery Nitric Oxide Synthase Isoforms in Patients Undergoing Coronary Artery Bypass Grafting.
IS  - 12
VL  - 10
DO  - 10.3390/antiox10121910
SP  - 1910
ER  - 
@article{
author = "Janković, Aleksandra and Zakić, Tamara and Miličić, Miroslav and Unić-Stojanović, Dragana and Kalezić, Anđelika and Korać, Aleksandra and Jović, Miomir and Korać, Bato",
year = "2021",
abstract = "Remote ischaemic preconditioning (RIPC) is a medical procedure that consists of repeated brief periods of transient ischaemia and reperfusion of distant organs (limbs) with the ability to provide internal organ protection from ischaemia. Even though RIPC has been successfully applied in patients with myocardial infarction during coronary revascularization (surgery/percutaneous angioplasty), the underlying molecular mechanisms are yet to be clarified. Thus, our study aimed to determine the role of nitric oxide synthase (NOS) isoforms in RIPC-induced protection (3 × 5 min of forearm ischaemia with 5 min of reperfusion) of arterial graft in patients undergoing urgent coronary artery bypass grafting (CABG). We examined RIPC effects on specific expression and immunolocalization of three NOS isoforms - endothelial (eNOS), inducible (iNOS) and neuronal (nNOS) in patients' internal thoracic artery (ITA) used as a graft. We found that the application of RIPC protocol leads to an increased protein expression of eNOS, which was further confirmed with strong eNOS immunopositivity, especially in the endothelium and smooth muscle cells of ITA. The same analysis of two other NOS isoforms, iNOS and nNOS, showed no significant differences between patients undergoing CABG with or without RIPC. Our results demonstrate RIPC-induced upregulation of eNOS in human ITA, pointing to its significance in achieving protective phenotype on a systemic level with important implications for graft patency.",
publisher = "Basel: MDPI",
journal = "Antioxidants (Basel, Switzerland)",
title = "Effects of Remote Ischaemic Preconditioning on the Internal Thoracic Artery Nitric Oxide Synthase Isoforms in Patients Undergoing Coronary Artery Bypass Grafting.",
number = "12",
volume = "10",
doi = "10.3390/antiox10121910",
pages = "1910"
}
Janković, A., Zakić, T., Miličić, M., Unić-Stojanović, D., Kalezić, A., Korać, A., Jović, M.,& Korać, B.. (2021). Effects of Remote Ischaemic Preconditioning on the Internal Thoracic Artery Nitric Oxide Synthase Isoforms in Patients Undergoing Coronary Artery Bypass Grafting.. in Antioxidants (Basel, Switzerland)
Basel: MDPI., 10(12), 1910.
https://doi.org/10.3390/antiox10121910
Janković A, Zakić T, Miličić M, Unić-Stojanović D, Kalezić A, Korać A, Jović M, Korać B. Effects of Remote Ischaemic Preconditioning on the Internal Thoracic Artery Nitric Oxide Synthase Isoforms in Patients Undergoing Coronary Artery Bypass Grafting.. in Antioxidants (Basel, Switzerland). 2021;10(12):1910.
doi:10.3390/antiox10121910 .
Janković, Aleksandra, Zakić, Tamara, Miličić, Miroslav, Unić-Stojanović, Dragana, Kalezić, Anđelika, Korać, Aleksandra, Jović, Miomir, Korać, Bato, "Effects of Remote Ischaemic Preconditioning on the Internal Thoracic Artery Nitric Oxide Synthase Isoforms in Patients Undergoing Coronary Artery Bypass Grafting." in Antioxidants (Basel, Switzerland), 10, no. 12 (2021):1910,
https://doi.org/10.3390/antiox10121910 . .
2
2

Nrf2-dependent control of redox and metabolic profile in the skin of hibernating ground squirrel (Spermophilus citellus)

Budnar, Marta; Zakić, Tamara; Ćirović, Duško; Kalezić, Anđelika; Korać, Aleksandra; Janković, Aleksandra; Korać, Bato

(Elsevier Inc., 2021)

TY  - CONF
AU  - Budnar, Marta
AU  - Zakić, Tamara
AU  - Ćirović, Duško
AU  - Kalezić, Anđelika
AU  - Korać, Aleksandra
AU  - Janković, Aleksandra
AU  - Korać, Bato
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4805
AB  - Hibernators enter into an extreme state of prolonged torpor characterized by hypometabolism (over 95% metabolic suppression), significant suppression of vital functions, and hypothermia. Specific regulatory mechanisms control physiological processes and metabolic functions that allow hibernators to survive challenging environmental conditions. Skin is one of the most metabolically active organs with intense fluctuations in metabolic rates that are accompanied by adequate changes in the antioxidant status. However, there is little data concerning redox-metabolic-related changes in hibernators skin. This study aimed to investigate nuclear factor erythroid 2–related factor 2 (Nrf2)-dependent control of redox and metabolic responses in the skin (epidermis and dermis) of ground squirrel (Spermophilus citellus) in pre-hibernation, hibernation (torpor), and post-hibernation. To that end, we examined the protein expression of Nrf2, hypoxia-inducible factor 1 alpha (HIF-1α), and key antioxidant defense (AD) and metabolic enzymes. Our results showed no change in HIF-1α protein expression during circannual phases, indicating that skin is not hypoxic during hibernation. Moreover, Nrf2 was strongly elevated in hibernation and post-hibernation, accompanied by higher methionine sulfoxide reductase A protein expression in hibernation. Interestingly, in hibernation protein levels of most AD enzymes remain on pre-hibernation level, while post-hibernation was characterized by high expression of manganese superoxide dismutase and glutathione peroxidase, indicating a possible role of Nrf2 in preconditioning during hibernation. Indeed, such AD and Nrf2 increases correlated with upregulation of pyruvate dehydrogenase, citrate synthase, complex III of the mitochondrial electron transport chain, and fatty acid synthase in hibernation and post-hibernation, and with an additional increase in enzymes of mitochondrial and peroxisomal β-oxidation in post-hibernation. The results suggest that Nrf2 is involved in the regulation of complex antioxidant response concerning changes in metabolic activity in the skin of ground squirrel in hibernation and post-hibernation to maintain optimal conditions for surviving.
PB  - Elsevier Inc.
C3  - Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
T1  - Nrf2-dependent control of redox and metabolic profile in the skin of hibernating ground squirrel (Spermophilus citellus)
DO  - 10.1016/j.freeradbiomed.2021.08.060
SP  - S65
ER  - 
@conference{
author = "Budnar, Marta and Zakić, Tamara and Ćirović, Duško and Kalezić, Anđelika and Korać, Aleksandra and Janković, Aleksandra and Korać, Bato",
year = "2021",
abstract = "Hibernators enter into an extreme state of prolonged torpor characterized by hypometabolism (over 95% metabolic suppression), significant suppression of vital functions, and hypothermia. Specific regulatory mechanisms control physiological processes and metabolic functions that allow hibernators to survive challenging environmental conditions. Skin is one of the most metabolically active organs with intense fluctuations in metabolic rates that are accompanied by adequate changes in the antioxidant status. However, there is little data concerning redox-metabolic-related changes in hibernators skin. This study aimed to investigate nuclear factor erythroid 2–related factor 2 (Nrf2)-dependent control of redox and metabolic responses in the skin (epidermis and dermis) of ground squirrel (Spermophilus citellus) in pre-hibernation, hibernation (torpor), and post-hibernation. To that end, we examined the protein expression of Nrf2, hypoxia-inducible factor 1 alpha (HIF-1α), and key antioxidant defense (AD) and metabolic enzymes. Our results showed no change in HIF-1α protein expression during circannual phases, indicating that skin is not hypoxic during hibernation. Moreover, Nrf2 was strongly elevated in hibernation and post-hibernation, accompanied by higher methionine sulfoxide reductase A protein expression in hibernation. Interestingly, in hibernation protein levels of most AD enzymes remain on pre-hibernation level, while post-hibernation was characterized by high expression of manganese superoxide dismutase and glutathione peroxidase, indicating a possible role of Nrf2 in preconditioning during hibernation. Indeed, such AD and Nrf2 increases correlated with upregulation of pyruvate dehydrogenase, citrate synthase, complex III of the mitochondrial electron transport chain, and fatty acid synthase in hibernation and post-hibernation, and with an additional increase in enzymes of mitochondrial and peroxisomal β-oxidation in post-hibernation. The results suggest that Nrf2 is involved in the regulation of complex antioxidant response concerning changes in metabolic activity in the skin of ground squirrel in hibernation and post-hibernation to maintain optimal conditions for surviving.",
publisher = "Elsevier Inc.",
journal = "Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia",
title = "Nrf2-dependent control of redox and metabolic profile in the skin of hibernating ground squirrel (Spermophilus citellus)",
doi = "10.1016/j.freeradbiomed.2021.08.060",
pages = "S65"
}
Budnar, M., Zakić, T., Ćirović, D., Kalezić, A., Korać, A., Janković, A.,& Korać, B.. (2021). Nrf2-dependent control of redox and metabolic profile in the skin of hibernating ground squirrel (Spermophilus citellus). in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia
Elsevier Inc.., S65.
https://doi.org/10.1016/j.freeradbiomed.2021.08.060
Budnar M, Zakić T, Ćirović D, Kalezić A, Korać A, Janković A, Korać B. Nrf2-dependent control of redox and metabolic profile in the skin of hibernating ground squirrel (Spermophilus citellus). in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia. 2021;:S65.
doi:10.1016/j.freeradbiomed.2021.08.060 .
Budnar, Marta, Zakić, Tamara, Ćirović, Duško, Kalezić, Anđelika, Korać, Aleksandra, Janković, Aleksandra, Korać, Bato, "Nrf2-dependent control of redox and metabolic profile in the skin of hibernating ground squirrel (Spermophilus citellus)" in Free Radical Research Europe (SFRR-E) Annual Meeting Abstracts “Redox biology in the 21st century: a new scientific discipline” 15-18 June 2021, Belgrade, Serbia (2021):S65,
https://doi.org/10.1016/j.freeradbiomed.2021.08.060 . .

Vitamin C biochemistry: From scurvy to COVID-19 treatment

Zakić, Tamara; Budnar, Marta; Kalezić, Anđelika; Korać, Aleksandra; Janković, Aleksandra; Korać, Bato

(Belgrade: Serbian Nutrition Society, 2020)

TY  - JOUR
AU  - Zakić, Tamara
AU  - Budnar, Marta
AU  - Kalezić, Anđelika
AU  - Korać, Aleksandra
AU  - Janković, Aleksandra
AU  - Korać, Bato
PY  - 2020
UR  - http://hrana-ishrana.org/wp-content/uploads/2021/03/Broj-2-Vol-61-2020-1.pdf
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4179
AB  - Priča o vitaminu C (L-askorbinska kiselina), antioksidansu i kofaktoru u brojnim
biohemijskim reakcijama, deo je njegove duge istorije danas dobro poznata.
Međutim, mnoga pitanja o mehanizmima njegovog delovanja i koristima
koje on ostvaruje po ljudsko zdravlje se kontinuirano nameću. Ovo se
odnosi ne samo na preporučene doze vitamina C, već i na način njegove primene.
Pored toga, postoje brojna pitanja o efikasnosti vitamina C u terapiji
različitih humanih infektivnih bolesti, njegovom antivirusnom potencijalu,
kao i ulozi u funkcionisanju imunskog sistema. Činjenica da vitamin C može
delovati kao redukciono sredstvo (antioksidant) i pro-oksidativno, dodatno
naglašava njegov oksidaciono-redukcioni (redoks) potencijal u fiziološkim
uslovima. Danas posebnu pažnja zahteva pitanje efekta intravenske primene
vitamina C kod pacijenata sa SARS-CoV-2. Ovaj pregled ima za cilj da
prikaže poznate činjenice o vitaminu C i njegovim mehanizmima delovanja
kako bi se bolje razumeli novi izazovi povezani sa vitaminom C.
AB  - The story of vitamin C (L-ascorbic acid) as an antioxidant and a cofactor
in numerous biochemical reactions is a part of its long history and
it is well known today. However, many questions of its mechanism of
action and the benefits that it has on human health are still emerging.
This applies not only to the recommended doses but also to the route
of its administration. Besides, there are numerous questions about the
therapeutic efficacy of vitamin C in various human (infectious) diseases,
as well as its immune system function and antiviral potential.
The fact that vitamin C can act as a reductant (antioxidant) and a prooxidant
further emphasizes its oxidation-reduction (redox) potential
in real physiological conditions. Today, the question of the intravenous
administration of vitamin C effect in patients with SARS-CoV-2
requires special attention. This review aims to showcase known facts
about vitamin C and its mechanisms of action to better understand
the current new challenges related to vitamin C.
PB  - Belgrade: Serbian Nutrition Society
T2  - Hrana i ishrana
T1  - Vitamin C biochemistry: From scurvy to COVID-19 treatment
T1  - Biohemija vitamina C: Od skorbuta do COVID-19 tretmana
IS  - 2
VL  - 61
DO  - 10.5937/hraIsh2002059Z
SP  - 59
EP  - 70
ER  - 
@article{
author = "Zakić, Tamara and Budnar, Marta and Kalezić, Anđelika and Korać, Aleksandra and Janković, Aleksandra and Korać, Bato",
year = "2020",
abstract = "Priča o vitaminu C (L-askorbinska kiselina), antioksidansu i kofaktoru u brojnim
biohemijskim reakcijama, deo je njegove duge istorije danas dobro poznata.
Međutim, mnoga pitanja o mehanizmima njegovog delovanja i koristima
koje on ostvaruje po ljudsko zdravlje se kontinuirano nameću. Ovo se
odnosi ne samo na preporučene doze vitamina C, već i na način njegove primene.
Pored toga, postoje brojna pitanja o efikasnosti vitamina C u terapiji
različitih humanih infektivnih bolesti, njegovom antivirusnom potencijalu,
kao i ulozi u funkcionisanju imunskog sistema. Činjenica da vitamin C može
delovati kao redukciono sredstvo (antioksidant) i pro-oksidativno, dodatno
naglašava njegov oksidaciono-redukcioni (redoks) potencijal u fiziološkim
uslovima. Danas posebnu pažnja zahteva pitanje efekta intravenske primene
vitamina C kod pacijenata sa SARS-CoV-2. Ovaj pregled ima za cilj da
prikaže poznate činjenice o vitaminu C i njegovim mehanizmima delovanja
kako bi se bolje razumeli novi izazovi povezani sa vitaminom C., The story of vitamin C (L-ascorbic acid) as an antioxidant and a cofactor
in numerous biochemical reactions is a part of its long history and
it is well known today. However, many questions of its mechanism of
action and the benefits that it has on human health are still emerging.
This applies not only to the recommended doses but also to the route
of its administration. Besides, there are numerous questions about the
therapeutic efficacy of vitamin C in various human (infectious) diseases,
as well as its immune system function and antiviral potential.
The fact that vitamin C can act as a reductant (antioxidant) and a prooxidant
further emphasizes its oxidation-reduction (redox) potential
in real physiological conditions. Today, the question of the intravenous
administration of vitamin C effect in patients with SARS-CoV-2
requires special attention. This review aims to showcase known facts
about vitamin C and its mechanisms of action to better understand
the current new challenges related to vitamin C.",
publisher = "Belgrade: Serbian Nutrition Society",
journal = "Hrana i ishrana",
title = "Vitamin C biochemistry: From scurvy to COVID-19 treatment, Biohemija vitamina C: Od skorbuta do COVID-19 tretmana",
number = "2",
volume = "61",
doi = "10.5937/hraIsh2002059Z",
pages = "59-70"
}
Zakić, T., Budnar, M., Kalezić, A., Korać, A., Janković, A.,& Korać, B.. (2020). Vitamin C biochemistry: From scurvy to COVID-19 treatment. in Hrana i ishrana
Belgrade: Serbian Nutrition Society., 61(2), 59-70.
https://doi.org/10.5937/hraIsh2002059Z
Zakić T, Budnar M, Kalezić A, Korać A, Janković A, Korać B. Vitamin C biochemistry: From scurvy to COVID-19 treatment. in Hrana i ishrana. 2020;61(2):59-70.
doi:10.5937/hraIsh2002059Z .
Zakić, Tamara, Budnar, Marta, Kalezić, Anđelika, Korać, Aleksandra, Janković, Aleksandra, Korać, Bato, "Vitamin C biochemistry: From scurvy to COVID-19 treatment" in Hrana i ishrana, 61, no. 2 (2020):59-70,
https://doi.org/10.5937/hraIsh2002059Z . .
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