TY  - JOUR
AU  - Paunović, Verica
AU  - Vučićević, Ljubica
AU  - Misirkić Marjanović, Maja
AU  - Perović, Vladimir
AU  - Ristić, Biljana
AU  - Bošnjak, Mihajlo
AU  - Mandić, Miloš
AU  - Stevanović, Danijela
AU  - Harhaji-Trajković, Ljubica
AU  - Lalošević, Jovan
AU  - Nikolić, Miloš
AU  - Bonači-Nikolić, Branka
AU  - Trajković, Vladimir
PY  - 2023
UR  - https://www.mdpi.com/2073-4409/12/9/1282
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5912
AB  - As autophagy can promote or inhibit inflammation, we examined autophagy-inflammation interplay in COVID-19. Autophagy markers in the blood of 19 control subjects and 26 COVID-19 patients at hospital admission and one week later were measured by ELISA, while cytokine levels were examined by flow cytometric bead immunoassay. The antiviral IFN-α and proinflammatory TNF, IL-6, IL-8, IL-17, IL-33, and IFN-γ were elevated in COVID-19 patients at both time points, while IL-10 and IL-1β were increased at admission and one week later, respectively. Autophagy markers LC3 and ATG5 were unaltered in COVID-19. In contrast, the concentration of autophagic cargo receptor p62 was significantly lower and positively correlated with TNF, IL-10, IL-17, and IL-33 at hospital admission, returning to normal levels after one week. The expression of SARS-CoV-2 proteins NSP5 or ORF3a in THP-1 monocytes caused an autophagy-independent decrease or autophagy-inhibition-dependent increase, respectively, of intracellular/secreted p62, as confirmed by immunoblot/ELISA. This was associated with an NSP5-mediated decrease in TNF/IL-10 mRNA and an ORF3a-mediated increase in TNF/IL-1β/IL-6/IL-10/IL-33 mRNA levels. A genetic knockdown of p62 mimicked the immunosuppressive effect of NSP5, and a p62 increase in autophagy-deficient cells mirrored the immunostimulatory action of ORF3a. In conclusion, the proinflammatory autophagy receptor p62 is reduced inacute COVID-19, and the balance between autophagy-independent decrease and autophagy blockade-dependent increase of p62 levels could affect SARS-CoV-induced inflammation.
PB  - Basel: MDPI
T2  - Cells
T1  - Autophagy Receptor p62 Regulates SARS-CoV-2-Induced Inflammation in COVID-19
IS  - 9
VL  - 12
DO  - 10.3390/cells12091282
SP  - 1282
ER  - 

@article{
author = "Paunović, Verica and Vučićević, Ljubica and Misirkić Marjanović, Maja and Perović, Vladimir and Ristić, Biljana and Bošnjak, Mihajlo and Mandić, Miloš and Stevanović, Danijela and Harhaji-Trajković, Ljubica and Lalošević, Jovan and Nikolić, Miloš and Bonači-Nikolić, Branka and Trajković, Vladimir",
year = "2023",
abstract = "As autophagy can promote or inhibit inflammation, we examined autophagy-inflammation interplay in COVID-19. Autophagy markers in the blood of 19 control subjects and 26 COVID-19 patients at hospital admission and one week later were measured by ELISA, while cytokine levels were examined by flow cytometric bead immunoassay. The antiviral IFN-α and proinflammatory TNF, IL-6, IL-8, IL-17, IL-33, and IFN-γ were elevated in COVID-19 patients at both time points, while IL-10 and IL-1β were increased at admission and one week later, respectively. Autophagy markers LC3 and ATG5 were unaltered in COVID-19. In contrast, the concentration of autophagic cargo receptor p62 was significantly lower and positively correlated with TNF, IL-10, IL-17, and IL-33 at hospital admission, returning to normal levels after one week. The expression of SARS-CoV-2 proteins NSP5 or ORF3a in THP-1 monocytes caused an autophagy-independent decrease or autophagy-inhibition-dependent increase, respectively, of intracellular/secreted p62, as confirmed by immunoblot/ELISA. This was associated with an NSP5-mediated decrease in TNF/IL-10 mRNA and an ORF3a-mediated increase in TNF/IL-1β/IL-6/IL-10/IL-33 mRNA levels. A genetic knockdown of p62 mimicked the immunosuppressive effect of NSP5, and a p62 increase in autophagy-deficient cells mirrored the immunostimulatory action of ORF3a. In conclusion, the proinflammatory autophagy receptor p62 is reduced inacute COVID-19, and the balance between autophagy-independent decrease and autophagy blockade-dependent increase of p62 levels could affect SARS-CoV-induced inflammation.",
publisher = "Basel: MDPI",
journal = "Cells",
title = "Autophagy Receptor p62 Regulates SARS-CoV-2-Induced Inflammation in COVID-19",
number = "9",
volume = "12",
doi = "10.3390/cells12091282",
pages = "1282"
}

Paunović, V., Vučićević, L., Misirkić Marjanović, M., Perović, V., Ristić, B., Bošnjak, M., Mandić, M., Stevanović, D., Harhaji-Trajković, L., Lalošević, J., Nikolić, M., Bonači-Nikolić, B.,& Trajković, V.. (2023). Autophagy Receptor p62 Regulates SARS-CoV-2-Induced Inflammation in COVID-19. in Cells
Basel: MDPI., 12(9), 1282.
https://doi.org/10.3390/cells12091282

Paunović V, Vučićević L, Misirkić Marjanović M, Perović V, Ristić B, Bošnjak M, Mandić M, Stevanović D, Harhaji-Trajković L, Lalošević J, Nikolić M, Bonači-Nikolić B, Trajković V. Autophagy Receptor p62 Regulates SARS-CoV-2-Induced Inflammation in COVID-19. in Cells. 2023;12(9):1282.
doi:10.3390/cells12091282 .

Paunović, Verica, Vučićević, Ljubica, Misirkić Marjanović, Maja, Perović, Vladimir, Ristić, Biljana, Bošnjak, Mihajlo, Mandić, Miloš, Stevanović, Danijela, Harhaji-Trajković, Ljubica, Lalošević, Jovan, Nikolić, Miloš, Bonači-Nikolić, Branka, Trajković, Vladimir, "Autophagy Receptor p62 Regulates SARS-CoV-2-Induced Inflammation in COVID-19" in Cells, 12, no. 9 (2023):1282,
https://doi.org/10.3390/cells12091282 . .

TY  - CONF
AU  - Janjetović, Kristina
AU  - Stamenković, Marina
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
AU  - Despotović, Ana
AU  - Stevanović, Danijela
AU  - Mandić, Miloš
AU  - Kosić, Milica
AU  - Paunović, Verica
AU  - Vučićević, Ljubica
AU  - Misirkić Marjanović, Maja
AU  - Trajković, Vladimir
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5737
AB  - I pored stalnog napretka lečenja kancera, ova bolest ostaje druga po smrtnosti u svetu. Kako bi se skratio vremenski i finansijski zahtevan proces razvoja novih hemoterapeutika poslednjih desetak godina intezivno se radi na ispitivanju antikancerskog potencijala lekova koji se već koriste u terapiji drugih bolesti. U ovom radu smo proučavali potencijalni antikancerski efekat inhibitora protonske pumpe pantoprazola (PPZ), terapeutika koji se standardno koristi u lečenju kiselinskih gastrointestinalnih poremećaja. Citotoksični efekat PPZ je ispitivan u kulturama humanog U251 glioblastoma, humanog H460 nesitnoćelijskog karcinoma pluća i mišjeg B16 melanoma. Pokazano je da PPZ aktiviranoj apoptozi u svim ispitivanim ćelijskim linijama prethodi povećana produkcija reaktivnih vrsta kiseonika, depolarizacija mitohondrija i aktivacija kaspaza. U prisustvu PPZ detektovano je povećanje LC3 II proteina ukazujući na aktivaciju autofagije. Detaljnijim ispitivanjem mehanizma koji je u osnovi toksičnog efekta PPZ, utvrđeno je da PPZ aktivira AKT/AMPK signalni put u ispitivanim ćelijskim linijama i stimuliše AMPK zavisnu citoprotektivnu autofagiju u U251 i B16 ćelijskim linijama. Sa druge strane, autofagija aktivirana u ćelijama karcinoma pluća je citotoksična. Sumirano, PPZ ispoljava značajan antikancerski potencijal prema U251, H460 i B16 ćelijama izazivajući apoptozu, pri čemu uloga autofagije u smrti ćelija može biti citoprotektivna ili citotoksična i zavisi od tipa ćelija. Dodatna farmakološka modulacija autofagije mogla bi poboljšati antikancerski potencijal pantoprazola.
AB  - И поред сталног напретка лечења канцера, ова болест остаје друга по смртности у
свету. Како би се скратио временски и финансијски захтеван процес развоја нових
хемотерапеутика последњих десетак година интезивно се ради на испитивању
антиканцерског потенцијала лекова који се већ користе у терапији других болести.
У овом раду смо проучавали потенцијални антиканцерски ефекат инхибитора
протонске пумпе пантопразола (ППЗ), терапеутика који се стандардно користи у
лечењу киселинских гастроинтестиналних поремећаја. Цитотоксични ефекат ППЗ
је испитиван у културама хуманог U251 глиобластома, хуманог H460
неситноћелијског карцинома плућа и мишјег B16 меланома. Показано је да ППЗ
активираној апоптози у свим испитиваним ћелијским линијама претходи повећана
продукција реактивних врста кисеоника, деполаризација митохондрија и
активација каспаза. У присуству ППЗ детектовано је повећање LC3 II протеина
указујући на активацију аутофагије. Детаљнијим испитивањем механизма који је у
основи токсичног ефекта ППЗ, утврђено је да ППЗ активира AKT/AMPK сигнални
пут у испитиваним ћелијским линијама и стимулише AMPK зависну
цитопротективну аутофагију у U251 и B16 ћелијским линијама. Са друге стране,
аутофагија активирана у ћелијама карцинома плућа је цитотоксична. Сумирано,
ППЗ испољава значајан антиканцерски потенцијал према U251, H460 и B16
ћелијама изазивајући апоптозу, при чему улога аутофагије у смрти ћелија може
бити цитопротективна или цитотоксична и зависи од типа ћелија. Додатна
фармаколошка модулација аутофагије могла би побољшати антиканцерски
потенцијал пантопразола.
PB  - Belgrade: Serbian Biological Society
C3  - Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
T1  - Antikancerski potencijal inhibitora protonske pumpe pantoprazola
T1  - Антиканцерски потенцијал инхибитора протонске пумпе пантопразола
SP  - 285
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5737
ER  - 

@conference{
author = "Janjetović, Kristina and Stamenković, Marina and Tovilović-Kovačević, Gordana and Zogović, Nevena and Despotović, Ana and Stevanović, Danijela and Mandić, Miloš and Kosić, Milica and Paunović, Verica and Vučićević, Ljubica and Misirkić Marjanović, Maja and Trajković, Vladimir",
year = "2022",
abstract = "I pored stalnog napretka lečenja kancera, ova bolest ostaje druga po smrtnosti u svetu. Kako bi se skratio vremenski i finansijski zahtevan proces razvoja novih hemoterapeutika poslednjih desetak godina intezivno se radi na ispitivanju antikancerskog potencijala lekova koji se već koriste u terapiji drugih bolesti. U ovom radu smo proučavali potencijalni antikancerski efekat inhibitora protonske pumpe pantoprazola (PPZ), terapeutika koji se standardno koristi u lečenju kiselinskih gastrointestinalnih poremećaja. Citotoksični efekat PPZ je ispitivan u kulturama humanog U251 glioblastoma, humanog H460 nesitnoćelijskog karcinoma pluća i mišjeg B16 melanoma. Pokazano je da PPZ aktiviranoj apoptozi u svim ispitivanim ćelijskim linijama prethodi povećana produkcija reaktivnih vrsta kiseonika, depolarizacija mitohondrija i aktivacija kaspaza. U prisustvu PPZ detektovano je povećanje LC3 II proteina ukazujući na aktivaciju autofagije. Detaljnijim ispitivanjem mehanizma koji je u osnovi toksičnog efekta PPZ, utvrđeno je da PPZ aktivira AKT/AMPK signalni put u ispitivanim ćelijskim linijama i stimuliše AMPK zavisnu citoprotektivnu autofagiju u U251 i B16 ćelijskim linijama. Sa druge strane, autofagija aktivirana u ćelijama karcinoma pluća je citotoksična. Sumirano, PPZ ispoljava značajan antikancerski potencijal prema U251, H460 i B16 ćelijama izazivajući apoptozu, pri čemu uloga autofagije u smrti ćelija može biti citoprotektivna ili citotoksična i zavisi od tipa ćelija. Dodatna farmakološka modulacija autofagije mogla bi poboljšati antikancerski potencijal pantoprazola., И поред сталног напретка лечења канцера, ова болест остаје друга по смртности у
свету. Како би се скратио временски и финансијски захтеван процес развоја нових
хемотерапеутика последњих десетак година интезивно се ради на испитивању
антиканцерског потенцијала лекова који се већ користе у терапији других болести.
У овом раду смо проучавали потенцијални антиканцерски ефекат инхибитора
протонске пумпе пантопразола (ППЗ), терапеутика који се стандардно користи у
лечењу киселинских гастроинтестиналних поремећаја. Цитотоксични ефекат ППЗ
је испитиван у културама хуманог U251 глиобластома, хуманог H460
неситноћелијског карцинома плућа и мишјег B16 меланома. Показано је да ППЗ
активираној апоптози у свим испитиваним ћелијским линијама претходи повећана
продукција реактивних врста кисеоника, деполаризација митохондрија и
активација каспаза. У присуству ППЗ детектовано је повећање LC3 II протеина
указујући на активацију аутофагије. Детаљнијим испитивањем механизма који је у
основи токсичног ефекта ППЗ, утврђено је да ППЗ активира AKT/AMPK сигнални
пут у испитиваним ћелијским линијама и стимулише AMPK зависну
цитопротективну аутофагију у U251 и B16 ћелијским линијама. Са друге стране,
аутофагија активирана у ћелијама карцинома плућа је цитотоксична. Сумирано,
ППЗ испољава значајан антиканцерски потенцијал према U251, H460 и B16
ћелијама изазивајући апоптозу, при чему улога аутофагије у смрти ћелија може
бити цитопротективна или цитотоксична и зависи од типа ћелија. Додатна
фармаколошка модулација аутофагије могла би побољшати антиканцерски
потенцијал пантопразола.",
publisher = "Belgrade: Serbian Biological Society",
journal = "Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia",
title = "Antikancerski potencijal inhibitora protonske pumpe pantoprazola, Антиканцерски потенцијал инхибитора протонске пумпе пантопразола",
pages = "285",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5737"
}

Janjetović, K., Stamenković, M., Tovilović-Kovačević, G., Zogović, N., Despotović, A., Stevanović, D., Mandić, M., Kosić, M., Paunović, V., Vučićević, L., Misirkić Marjanović, M.,& Trajković, V.. (2022). Antikancerski potencijal inhibitora protonske pumpe pantoprazola. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
Belgrade: Serbian Biological Society., 285.
https://hdl.handle.net/21.15107/rcub_ibiss_5737

Janjetović K, Stamenković M, Tovilović-Kovačević G, Zogović N, Despotović A, Stevanović D, Mandić M, Kosić M, Paunović V, Vučićević L, Misirkić Marjanović M, Trajković V. Antikancerski potencijal inhibitora protonske pumpe pantoprazola. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia. 2022;:285.
https://hdl.handle.net/21.15107/rcub_ibiss_5737 .

Janjetović, Kristina, Stamenković, Marina, Tovilović-Kovačević, Gordana, Zogović, Nevena, Despotović, Ana, Stevanović, Danijela, Mandić, Miloš, Kosić, Milica, Paunović, Verica, Vučićević, Ljubica, Misirkić Marjanović, Maja, Trajković, Vladimir, "Antikancerski potencijal inhibitora protonske pumpe pantoprazola" in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia (2022):285,
https://hdl.handle.net/21.15107/rcub_ibiss_5737 .

TY  - JOUR
AU  - Kosić, Milica
AU  - Paunović, Verica
AU  - Ristić, Biljana
AU  - Mirčić, Aleksandar
AU  - Bošnjak, Mihajlo
AU  - Stevanović, Danijela
AU  - Kravić-Stevović, Tamara K
AU  - Trajković, Vladimir
AU  - Harhaji-Trajković, Ljubica
PY  - 2021
UR  - https://www.sciencedirect.com/science/article/pii/S1347861321000591
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4427
AB  - We investigated the effect of 3-methyladenine (3MA), a class III phosphatidylinositol 3-kinase (PI3K)-blocking autophagy inhibitor, on cancer cell death induced by simultaneous inhibition of glycolysis by 2-deoxyglucose (2DG) and mitochondrial respiration by rotenone. 2DG/rotenone reduced ATP levels and increased mitochondrial superoxide production, causing mitochondrial swelling and necrotic death in various cancer cell lines. 2DG/rotenone failed to increase proautophagic beclin-1 and autophagic flux in melanoma cells despite the activation of AMP-activated protein kinase (AMPK) and inhibition of mechanistic target of rapamycin complex 1 (mTORC1). 3MA, but not autophagy inhibition with other PI3K and lysosomal inhibitors, attenuated 2DG/rotenone-induced mitochondrial damage, oxidative stress, ATP depletion, and cell death, while antioxidant treatment mimicked its protective action. The protection was not mediated by autophagy upregulation via class I PI3K/Akt inhibition, as it was preserved in cells with genetically inhibited autophagy. 3MA increased AMPK and mTORC1 activation in energy-stressed cells, but neither AMPK nor mTORC1 inhibition reduced its cytoprotective effect. 3MA reduced JNK activation, and JNK pharmacological/genetic suppression mimicked its mitochondria-preserving and cytoprotective activity. Therefore, 3MA prevents energy stress-triggered cancer cell death through autophagy-independent mechanisms possibly involving JNK suppression and decrease of oxidative stress. Our results warrant caution when using 3MA as an autophagy inhibitor.
PB  - Kyoto : Japanese Pharmacological Society
T2  - Journal of Pharmacological Sciences
T1  - 3-Methyladenine prevents energy stress-induced necrotic death of melanoma cells through autophagy-independent mechanisms
IS  - 1
VL  - 147
DO  - 10.1016/j.jphs.2021.06.003
SP  - 156
EP  - 167
ER  - 

@article{
author = "Kosić, Milica and Paunović, Verica and Ristić, Biljana and Mirčić, Aleksandar and Bošnjak, Mihajlo and Stevanović, Danijela and Kravić-Stevović, Tamara K and Trajković, Vladimir and Harhaji-Trajković, Ljubica",
year = "2021",
abstract = "We investigated the effect of 3-methyladenine (3MA), a class III phosphatidylinositol 3-kinase (PI3K)-blocking autophagy inhibitor, on cancer cell death induced by simultaneous inhibition of glycolysis by 2-deoxyglucose (2DG) and mitochondrial respiration by rotenone. 2DG/rotenone reduced ATP levels and increased mitochondrial superoxide production, causing mitochondrial swelling and necrotic death in various cancer cell lines. 2DG/rotenone failed to increase proautophagic beclin-1 and autophagic flux in melanoma cells despite the activation of AMP-activated protein kinase (AMPK) and inhibition of mechanistic target of rapamycin complex 1 (mTORC1). 3MA, but not autophagy inhibition with other PI3K and lysosomal inhibitors, attenuated 2DG/rotenone-induced mitochondrial damage, oxidative stress, ATP depletion, and cell death, while antioxidant treatment mimicked its protective action. The protection was not mediated by autophagy upregulation via class I PI3K/Akt inhibition, as it was preserved in cells with genetically inhibited autophagy. 3MA increased AMPK and mTORC1 activation in energy-stressed cells, but neither AMPK nor mTORC1 inhibition reduced its cytoprotective effect. 3MA reduced JNK activation, and JNK pharmacological/genetic suppression mimicked its mitochondria-preserving and cytoprotective activity. Therefore, 3MA prevents energy stress-triggered cancer cell death through autophagy-independent mechanisms possibly involving JNK suppression and decrease of oxidative stress. Our results warrant caution when using 3MA as an autophagy inhibitor.",
publisher = "Kyoto : Japanese Pharmacological Society",
journal = "Journal of Pharmacological Sciences",
title = "3-Methyladenine prevents energy stress-induced necrotic death of melanoma cells through autophagy-independent mechanisms",
number = "1",
volume = "147",
doi = "10.1016/j.jphs.2021.06.003",
pages = "156-167"
}

Kosić, M., Paunović, V., Ristić, B., Mirčić, A., Bošnjak, M., Stevanović, D., Kravić-Stevović, T. K., Trajković, V.,& Harhaji-Trajković, L.. (2021). 3-Methyladenine prevents energy stress-induced necrotic death of melanoma cells through autophagy-independent mechanisms. in Journal of Pharmacological Sciences
Kyoto : Japanese Pharmacological Society., 147(1), 156-167.
https://doi.org/10.1016/j.jphs.2021.06.003

Kosić M, Paunović V, Ristić B, Mirčić A, Bošnjak M, Stevanović D, Kravić-Stevović TK, Trajković V, Harhaji-Trajković L. 3-Methyladenine prevents energy stress-induced necrotic death of melanoma cells through autophagy-independent mechanisms. in Journal of Pharmacological Sciences. 2021;147(1):156-167.
doi:10.1016/j.jphs.2021.06.003 .

Kosić, Milica, Paunović, Verica, Ristić, Biljana, Mirčić, Aleksandar, Bošnjak, Mihajlo, Stevanović, Danijela, Kravić-Stevović, Tamara K, Trajković, Vladimir, Harhaji-Trajković, Ljubica, "3-Methyladenine prevents energy stress-induced necrotic death of melanoma cells through autophagy-independent mechanisms" in Journal of Pharmacological Sciences, 147, no. 1 (2021):156-167,
https://doi.org/10.1016/j.jphs.2021.06.003 . .

TY  - JOUR
AU  - Ristić, Biljana
AU  - Harhaji-Trajković, Ljubica
AU  - Bošnjak, Mihajlo
AU  - Dakić, Ivana
AU  - Mijatović, Srđan
AU  - Trajković, Vladimir
PY  - 2021
UR  - https://www.mdpi.com/2072-6694/13/16/4145
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4431
AB  - Graphene-based nanomaterials (GNM) are plausible candidates for cancer therapeutics
and drug delivery systems. Pure graphene and graphene oxide nanoparticles, as well as graphene
quantum dots and graphene nanofibers, were all able to trigger autophagy in cancer cells through both
transcriptional and post-transcriptional mechanisms involving oxidative/endoplasmic reticulum
stress, AMP-activated protein kinase, mechanistic target of rapamycin, mitogen-activated protein
kinase, and Toll-like receptor signaling. This was often coupled with lysosomal dysfunction and
subsequent blockade of autophagic flux, which additionally increased the accumulation of autophagy
mediators that participated in apoptotic, necrotic, or necroptotic death of cancer cells and influenced
the immune response against the tumor. In this review, we analyze molecular mechanisms and
structure–activity relationships of GNM-mediated autophagy modulation, its consequences for
cancer cell survival/death and anti-tumor immune response, and the possible implications for the
use of GNM in cancer therapy.
PB  - Basel : MDPI
T2  - Cancers
T1  - Modulation of Cancer Cell Autophagic Responses by Graphene-Based Nanomaterials: Molecular Mechanisms and Therapeutic Implications
IS  - 16
VL  - 13
DO  - 10.3390/cancers13164145
SP  - 4145
ER  - 

@article{
author = "Ristić, Biljana and Harhaji-Trajković, Ljubica and Bošnjak, Mihajlo and Dakić, Ivana and Mijatović, Srđan and Trajković, Vladimir",
year = "2021",
abstract = "Graphene-based nanomaterials (GNM) are plausible candidates for cancer therapeutics
and drug delivery systems. Pure graphene and graphene oxide nanoparticles, as well as graphene
quantum dots and graphene nanofibers, were all able to trigger autophagy in cancer cells through both
transcriptional and post-transcriptional mechanisms involving oxidative/endoplasmic reticulum
stress, AMP-activated protein kinase, mechanistic target of rapamycin, mitogen-activated protein
kinase, and Toll-like receptor signaling. This was often coupled with lysosomal dysfunction and
subsequent blockade of autophagic flux, which additionally increased the accumulation of autophagy
mediators that participated in apoptotic, necrotic, or necroptotic death of cancer cells and influenced
the immune response against the tumor. In this review, we analyze molecular mechanisms and
structure–activity relationships of GNM-mediated autophagy modulation, its consequences for
cancer cell survival/death and anti-tumor immune response, and the possible implications for the
use of GNM in cancer therapy.",
publisher = "Basel : MDPI",
journal = "Cancers",
title = "Modulation of Cancer Cell Autophagic Responses by Graphene-Based Nanomaterials: Molecular Mechanisms and Therapeutic Implications",
number = "16",
volume = "13",
doi = "10.3390/cancers13164145",
pages = "4145"
}

Ristić, B., Harhaji-Trajković, L., Bošnjak, M., Dakić, I., Mijatović, S.,& Trajković, V.. (2021). Modulation of Cancer Cell Autophagic Responses by Graphene-Based Nanomaterials: Molecular Mechanisms and Therapeutic Implications. in Cancers
Basel : MDPI., 13(16), 4145.
https://doi.org/10.3390/cancers13164145

Ristić B, Harhaji-Trajković L, Bošnjak M, Dakić I, Mijatović S, Trajković V. Modulation of Cancer Cell Autophagic Responses by Graphene-Based Nanomaterials: Molecular Mechanisms and Therapeutic Implications. in Cancers. 2021;13(16):4145.
doi:10.3390/cancers13164145 .

Ristić, Biljana, Harhaji-Trajković, Ljubica, Bošnjak, Mihajlo, Dakić, Ivana, Mijatović, Srđan, Trajković, Vladimir, "Modulation of Cancer Cell Autophagic Responses by Graphene-Based Nanomaterials: Molecular Mechanisms and Therapeutic Implications" in Cancers, 13, no. 16 (2021):4145,
https://doi.org/10.3390/cancers13164145 . .

TY  - CONF
AU  - Paunović, Verica
AU  - Kosić, Milica
AU  - Arsikin-Csordas, Katarina
AU  - Firestone, Raymond A
AU  - Ristić, Biljana
AU  - Mirčić, Aleksandar
AU  - Petričević, Saša
AU  - Bošnjak, Mihajlo
AU  - Zogović, Nevena
AU  - Mandić, Miloš
AU  - Bumbaširević, Vladimir
AU  - Trajković, Vladimir
AU  - Harhaji-Trajković, Ljubica
PY  - 2019
UR  - https://www.fens.org/news-activities/fens-and-societies-calendar/meeting-event/fens-regional-meeting-2019
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6355
AB  - During malignant transformation cells acquire changes in metabolism, signaling pathways as well as organelle content. The preferential use of aerobic glycolysis (Warburg effect), along with the increased number and volume of lysosomes can be viewed as glioma cells’ Achilles heels. In the present study, we aimed to examine the in vitro antiglioma effects of combining lysosomal membrane permeabilization (LMP)-inducing agent N-dodecylimidazole (NDI) with glycolytic inhibitor 2-deoxy-D-glucose (2DG).
NDI-triggered LMP and 2DG-mediated glycolysis block synergistically induced rapid ATP depletion, mitochondrial damage, and reactive oxygen species (ROS) production causing necrotic cell death of U251 glioma cells, but not primary astrocytes. Lysosomal cathepsin inhibitor E64 and antioxidant α-tocopherol partially prevented NDI/2DG-induced glioma cell death, thus implying the involvement of LMP and oxidative stress in the observed cytotoxicity. Likewise, LMP-inducing agent chloroquine
showed synergistic cytotoxic effect with 2DG. Similarly, glucose deprivation as well as other glycolytic inhibitors, iodoacetate and sodium fluoride, synergistically cooperated with NDI, further corroborating that the observed antiglioma effect of the NDI/2DG combined treatment was indeed based on LMP and glycolysis block. Based on these results, we concluded that NDI-triggered LMP caused initial mitochondrial damage, which was further increased by 2DG causing the lack of glycolytic ATP
required to maintain mitochondrial health. This created a positive feedback loop of mitochondrial dysfunction, ATP loss, and ROS production, culminating in necrosis. Therefore, the combination of glycolysis inhibitors and LMP-inducing agents seems promising antiglioma strategy.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
T1  - Synergistic antiglioma action of lysosomal membrane permeabilization and glycolysis inhibition
SP  - 213
EP  - 213
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6355
ER  - 

@conference{
author = "Paunović, Verica and Kosić, Milica and Arsikin-Csordas, Katarina and Firestone, Raymond A and Ristić, Biljana and Mirčić, Aleksandar and Petričević, Saša and Bošnjak, Mihajlo and Zogović, Nevena and Mandić, Miloš and Bumbaširević, Vladimir and Trajković, Vladimir and Harhaji-Trajković, Ljubica",
year = "2019",
abstract = "During malignant transformation cells acquire changes in metabolism, signaling pathways as well as organelle content. The preferential use of aerobic glycolysis (Warburg effect), along with the increased number and volume of lysosomes can be viewed as glioma cells’ Achilles heels. In the present study, we aimed to examine the in vitro antiglioma effects of combining lysosomal membrane permeabilization (LMP)-inducing agent N-dodecylimidazole (NDI) with glycolytic inhibitor 2-deoxy-D-glucose (2DG).
NDI-triggered LMP and 2DG-mediated glycolysis block synergistically induced rapid ATP depletion, mitochondrial damage, and reactive oxygen species (ROS) production causing necrotic cell death of U251 glioma cells, but not primary astrocytes. Lysosomal cathepsin inhibitor E64 and antioxidant α-tocopherol partially prevented NDI/2DG-induced glioma cell death, thus implying the involvement of LMP and oxidative stress in the observed cytotoxicity. Likewise, LMP-inducing agent chloroquine
showed synergistic cytotoxic effect with 2DG. Similarly, glucose deprivation as well as other glycolytic inhibitors, iodoacetate and sodium fluoride, synergistically cooperated with NDI, further corroborating that the observed antiglioma effect of the NDI/2DG combined treatment was indeed based on LMP and glycolysis block. Based on these results, we concluded that NDI-triggered LMP caused initial mitochondrial damage, which was further increased by 2DG causing the lack of glycolytic ATP
required to maintain mitochondrial health. This created a positive feedback loop of mitochondrial dysfunction, ATP loss, and ROS production, culminating in necrosis. Therefore, the combination of glycolysis inhibitors and LMP-inducing agents seems promising antiglioma strategy.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia",
title = "Synergistic antiglioma action of lysosomal membrane permeabilization and glycolysis inhibition",
pages = "213-213",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6355"
}

Paunović, V., Kosić, M., Arsikin-Csordas, K., Firestone, R. A., Ristić, B., Mirčić, A., Petričević, S., Bošnjak, M., Zogović, N., Mandić, M., Bumbaširević, V., Trajković, V.,& Harhaji-Trajković, L.. (2019). Synergistic antiglioma action of lysosomal membrane permeabilization and glycolysis inhibition. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 213-213.
https://hdl.handle.net/21.15107/rcub_ibiss_6355

Paunović V, Kosić M, Arsikin-Csordas K, Firestone RA, Ristić B, Mirčić A, Petričević S, Bošnjak M, Zogović N, Mandić M, Bumbaširević V, Trajković V, Harhaji-Trajković L. Synergistic antiglioma action of lysosomal membrane permeabilization and glycolysis inhibition. in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia. 2019;:213-213.
https://hdl.handle.net/21.15107/rcub_ibiss_6355 .

Paunović, Verica, Kosić, Milica, Arsikin-Csordas, Katarina, Firestone, Raymond A, Ristić, Biljana, Mirčić, Aleksandar, Petričević, Saša, Bošnjak, Mihajlo, Zogović, Nevena, Mandić, Miloš, Bumbaširević, Vladimir, Trajković, Vladimir, Harhaji-Trajković, Ljubica, "Synergistic antiglioma action of lysosomal membrane permeabilization and glycolysis inhibition" in Book of Abstract: Federation of European Neuroscience Societies (FENS) Regional Meeting; 2019 Jul 10-13; Belgrade, Serbia (2019):213-213,
https://hdl.handle.net/21.15107/rcub_ibiss_6355 .

TY  - JOUR
AU  - Paunović, V.
AU  - Kosić, M.
AU  - Đorđević, S.
AU  - Žugić, A.
AU  - Đalinac, N.
AU  - Gašić, U.
AU  - Trajković, Vladimir
AU  - Harhaji-Trajković, Ljubica
PY  - 2016
UR  - http://www.ncbi.nlm.nih.gov/pubmed/27755961
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2563
AB  - Marrubium vulgare is a European medicinal plant with numerous beneficial effects on human health. The aim of the study was to isolate the plant ethanolic extract (MVE) and to investigate its anti-melanoma and anti-glioma effects. MVE was prepared by the modified pharmacopoeial percolation method and characterized by UHPLC-LTQ OrbiTrap MS. MVE dose-dependently reduced viability of melanoma (B16) and glioma (U251) cells, but not peripheral blood mononuclear cells. It arrested cell cycle in S+G2/M phase, which was associated with the activation of MAP kinase p38 and up-regulation of antiproliferative genes p53, p21 and p27. MVE induced oxidative stress, while antioxidants abrogated its antitumor effect. Furthermore, MVE induced mitochondrial depolarization, activation of caspase-9 and -3, Parp cleavage, phosphatidylserine exposure and DNA fragmentation. The mitochondrial apoptotic pathway was associated with the up-regulation of proapoptotic genes Pten, Bak1, Apaf1, and Puma and down-regulation of antiapoptotic genes survivin and Xiap. MVE also stimulated the expression of autophagy-related genes Atg5, Atg7, Atg12, Beclin-1, Gabarab and Sqstm1, as well as LC3-I conversion to the autophagosome associated LC3-II, while autophagy inhibitors exacerbated its cytotoxicity. Finally, the most abundant phenolic components of MVE, ferulic, p-hydroxybenzoic, caffeic and chlorogenic acids, did not exert a profound effect on viability of tumor cells, suggesting that other components individually or in concert are the mediators of the extracts' cytotoxicity. By demonstrating the ability of MVE to inhibit proliferation, induce apoptosis and cytoprotective autophagy, our results suggest that MVE, alone or combined with autophagy inhibitors, could be a good candidate for anti-melanoma and anti-glioma therapy.
T2  - Cellular and molecular biology (Noisy-le-Grand, France)
T1  - Marrubium vulgare ethanolic extract induces proliferation block, apoptosis, and cytoprotective autophagy in cancer cells in vitro.
IS  - 11
VL  - 62
DO  - 10.14715/cmb/2016.62.11.18
SP  - 108
EP  - 114
ER  - 

@article{
author = "Paunović, V. and Kosić, M. and Đorđević, S. and Žugić, A. and Đalinac, N. and Gašić, U. and Trajković, Vladimir and Harhaji-Trajković, Ljubica",
year = "2016",
abstract = "Marrubium vulgare is a European medicinal plant with numerous beneficial effects on human health. The aim of the study was to isolate the plant ethanolic extract (MVE) and to investigate its anti-melanoma and anti-glioma effects. MVE was prepared by the modified pharmacopoeial percolation method and characterized by UHPLC-LTQ OrbiTrap MS. MVE dose-dependently reduced viability of melanoma (B16) and glioma (U251) cells, but not peripheral blood mononuclear cells. It arrested cell cycle in S+G2/M phase, which was associated with the activation of MAP kinase p38 and up-regulation of antiproliferative genes p53, p21 and p27. MVE induced oxidative stress, while antioxidants abrogated its antitumor effect. Furthermore, MVE induced mitochondrial depolarization, activation of caspase-9 and -3, Parp cleavage, phosphatidylserine exposure and DNA fragmentation. The mitochondrial apoptotic pathway was associated with the up-regulation of proapoptotic genes Pten, Bak1, Apaf1, and Puma and down-regulation of antiapoptotic genes survivin and Xiap. MVE also stimulated the expression of autophagy-related genes Atg5, Atg7, Atg12, Beclin-1, Gabarab and Sqstm1, as well as LC3-I conversion to the autophagosome associated LC3-II, while autophagy inhibitors exacerbated its cytotoxicity. Finally, the most abundant phenolic components of MVE, ferulic, p-hydroxybenzoic, caffeic and chlorogenic acids, did not exert a profound effect on viability of tumor cells, suggesting that other components individually or in concert are the mediators of the extracts' cytotoxicity. By demonstrating the ability of MVE to inhibit proliferation, induce apoptosis and cytoprotective autophagy, our results suggest that MVE, alone or combined with autophagy inhibitors, could be a good candidate for anti-melanoma and anti-glioma therapy.",
journal = "Cellular and molecular biology (Noisy-le-Grand, France)",
title = "Marrubium vulgare ethanolic extract induces proliferation block, apoptosis, and cytoprotective autophagy in cancer cells in vitro.",
number = "11",
volume = "62",
doi = "10.14715/cmb/2016.62.11.18",
pages = "108-114"
}

Paunović, V., Kosić, M., Đorđević, S., Žugić, A., Đalinac, N., Gašić, U., Trajković, V.,& Harhaji-Trajković, L.. (2016). Marrubium vulgare ethanolic extract induces proliferation block, apoptosis, and cytoprotective autophagy in cancer cells in vitro.. in Cellular and molecular biology (Noisy-le-Grand, France), 62(11), 108-114.
https://doi.org/10.14715/cmb/2016.62.11.18

Paunović V, Kosić M, Đorđević S, Žugić A, Đalinac N, Gašić U, Trajković V, Harhaji-Trajković L. Marrubium vulgare ethanolic extract induces proliferation block, apoptosis, and cytoprotective autophagy in cancer cells in vitro.. in Cellular and molecular biology (Noisy-le-Grand, France). 2016;62(11):108-114.
doi:10.14715/cmb/2016.62.11.18 .

Paunović, V., Kosić, M., Đorđević, S., Žugić, A., Đalinac, N., Gašić, U., Trajković, Vladimir, Harhaji-Trajković, Ljubica, "Marrubium vulgare ethanolic extract induces proliferation block, apoptosis, and cytoprotective autophagy in cancer cells in vitro." in Cellular and molecular biology (Noisy-le-Grand, France), 62, no. 11 (2016):108-114,
https://doi.org/10.14715/cmb/2016.62.11.18 . .

TY  - JOUR
AU  - Tovilović-Kovačević, Gordana
AU  - Ristić, Biljana
AU  - Šiljić, Marina
AU  - Nikolić, Valentina
AU  - Kravić-Stevović, Tamara
AU  - Dulović, Marija
AU  - Milenković, Marina
AU  - Knežević, Aleksandra
AU  - Bošnjak, Mihajlo
AU  - Bumbaširević, Vladimir
AU  - Stanojević, Maja
AU  - Trajković, Vladimir
PY  - 2013
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6345
AB  - We investigated the role of autophagy, a stress-inducible lysosomal self-digestion of cellular components, in modulation of herpes simplex virus type 1 (HSV-1)-triggered death of U251 human glioma cells. HSV-1 caused apoptotic death in U251 cells, characterized by phosphatidylserine externalization, caspase activation and DNA fragmentation. HSV-1-induced apoptosis was associated with the induction of autophagic response, as confirmed by the conversion of cytosolic LC3-I to autophagosome-associated LC3-II, increase in intracellular acidification, presence of autophagic vesicles, and increase in proteolysis of the selective autophagic target p62. HSV-1-triggered autophagy was not associated with the significant increase in the expression of proautophagic protein beclin-1 or downregulation of the major autophagy suppressor mammalian target of rapamycin (mTOR). Moreover, the phosphorylation of mTOR and its direct substrate p70 S6 kinase was augmented by HSV-1 infection, while the mTOR stimulator Akt and inhibitor AMPK-activated protein kinase (AMPK) were accordingly activated and suppressed, respectively. An shRNA-mediated knockdown of the autophagy-essential LC3b, as well as pharmacological inhibition of autophagy with bafilomycin A1 or 3-methyladenine, markedly accelerated apoptotic changes and ensuing cell death in HSV-1-infected glioma cells. These data indicate that AMPK/Akt/mTOR-independent autophagy could prolong survival of HSV-1-infected U251 glioma cells by counteracting the coinciding apoptotic response.
PB  - Elsevier Masson SAS
T2  - Microbes and Infection
T1  - mTOR-independent autophagy counteracts apoptosis in herpes simplex virus type 1-infected U251 glioma cells
IS  - 8-9
VL  - 15
DO  - 10.1016/j.micinf.2013.04.012
SP  - 615
EP  - 624
ER  - 

@article{
author = "Tovilović-Kovačević, Gordana and Ristić, Biljana and Šiljić, Marina and Nikolić, Valentina and Kravić-Stevović, Tamara and Dulović, Marija and Milenković, Marina and Knežević, Aleksandra and Bošnjak, Mihajlo and Bumbaširević, Vladimir and Stanojević, Maja and Trajković, Vladimir",
year = "2013",
abstract = "We investigated the role of autophagy, a stress-inducible lysosomal self-digestion of cellular components, in modulation of herpes simplex virus type 1 (HSV-1)-triggered death of U251 human glioma cells. HSV-1 caused apoptotic death in U251 cells, characterized by phosphatidylserine externalization, caspase activation and DNA fragmentation. HSV-1-induced apoptosis was associated with the induction of autophagic response, as confirmed by the conversion of cytosolic LC3-I to autophagosome-associated LC3-II, increase in intracellular acidification, presence of autophagic vesicles, and increase in proteolysis of the selective autophagic target p62. HSV-1-triggered autophagy was not associated with the significant increase in the expression of proautophagic protein beclin-1 or downregulation of the major autophagy suppressor mammalian target of rapamycin (mTOR). Moreover, the phosphorylation of mTOR and its direct substrate p70 S6 kinase was augmented by HSV-1 infection, while the mTOR stimulator Akt and inhibitor AMPK-activated protein kinase (AMPK) were accordingly activated and suppressed, respectively. An shRNA-mediated knockdown of the autophagy-essential LC3b, as well as pharmacological inhibition of autophagy with bafilomycin A1 or 3-methyladenine, markedly accelerated apoptotic changes and ensuing cell death in HSV-1-infected glioma cells. These data indicate that AMPK/Akt/mTOR-independent autophagy could prolong survival of HSV-1-infected U251 glioma cells by counteracting the coinciding apoptotic response.",
publisher = "Elsevier Masson SAS",
journal = "Microbes and Infection",
title = "mTOR-independent autophagy counteracts apoptosis in herpes simplex virus type 1-infected U251 glioma cells",
number = "8-9",
volume = "15",
doi = "10.1016/j.micinf.2013.04.012",
pages = "615-624"
}

Tovilović-Kovačević, G., Ristić, B., Šiljić, M., Nikolić, V., Kravić-Stevović, T., Dulović, M., Milenković, M., Knežević, A., Bošnjak, M., Bumbaširević, V., Stanojević, M.,& Trajković, V.. (2013). mTOR-independent autophagy counteracts apoptosis in herpes simplex virus type 1-infected U251 glioma cells. in Microbes and Infection
Elsevier Masson SAS., 15(8-9), 615-624.
https://doi.org/10.1016/j.micinf.2013.04.012

Tovilović-Kovačević G, Ristić B, Šiljić M, Nikolić V, Kravić-Stevović T, Dulović M, Milenković M, Knežević A, Bošnjak M, Bumbaširević V, Stanojević M, Trajković V. mTOR-independent autophagy counteracts apoptosis in herpes simplex virus type 1-infected U251 glioma cells. in Microbes and Infection. 2013;15(8-9):615-624.
doi:10.1016/j.micinf.2013.04.012 .

Tovilović-Kovačević, Gordana, Ristić, Biljana, Šiljić, Marina, Nikolić, Valentina, Kravić-Stevović, Tamara, Dulović, Marija, Milenković, Marina, Knežević, Aleksandra, Bošnjak, Mihajlo, Bumbaširević, Vladimir, Stanojević, Maja, Trajković, Vladimir, "mTOR-independent autophagy counteracts apoptosis in herpes simplex virus type 1-infected U251 glioma cells" in Microbes and Infection, 15, no. 8-9 (2013):615-624,
https://doi.org/10.1016/j.micinf.2013.04.012 . .

TY  - JOUR
AU  - Arsikin-Csordas, Katarina
AU  - Kravić-Stevović, Tamara
AU  - Jovanović, Maja
AU  - Ristić, Biljana
AU  - Tovilović-Kovačević, Gordana
AU  - Zogović, Nevena
AU  - Bumbaširević, Vladimir
AU  - Trajković, Vladimir
AU  - Harhaji-Trajković, Ljubica
PY  - 2012
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6366
AB  - The role of the main intracellular energy sensor adenosine monophosphate (AMP)-activated protein kinase (AMPK) in the induction of autophagic response and cell death was investigated in SH-SY5Y human neuroblastoma cells exposed to the dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA). The induction of autophagy in SH-SY5Y cells was demonstrated by acridine orange staining of intracellular acidic vesicles, the presence of autophagosome- and autophagolysosome-like vesicles confirmed by transmission electron microscopy, as well as by microtubule-associated protein 1 light-chain 3 (LC3) conversion and p62 degradation detected by immunoblotting. 6-OHDA induced phosphorylation of AMPK and its target Raptor, followed by the dephosphorylation of the major autophagy inhibitor mammalian target of rapamycin (mTOR) and its substrate p70S6 kinase (S6K). 6-OHDA treatment failed to suppress mTOR/S6K phosphorylation and to increase LC3 conversion, p62 degradation and cytoplasmatic acidification in neuroblastoma cells in which AMPK expression was downregulated by RNA interference. Transfection of SH-SY5Y cells with AMPK or LC3β shRNA, as well as treatment with pharmacological autophagy inhibitors suppressed, while mTOR inhibitor rapamycin potentiated 6-OHDA-induced oxidative stress and apoptotic cell death. 6-OHDA induced phosphorylation of p38 mitogen-activated protein (MAP) kinase in an AMPK-dependent manner, and pharmacological inhibition of p38 MAP kinase reduced neurotoxicity, but not AMPK activation and autophagy triggered by 6-OHDA. Finally, the antioxidant N-acetyl cysteine antagonized 6-OHDA-induced activation of AMPK, p38 and autophagy. These data suggest that oxidative stress-mediated AMPK/mTOR-dependent autophagy and AMPK/p38-dependent apoptosis could be valid therapeutic targets for neuroprotection.
PB  - Amsterdam: Elsevier
T2  - Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
T1  - Autophagy-dependent and -independent involvement of AMP-activated protein kinase in 6-hydroxydopamine toxicity to SH-SY5Y neuroblastoma cells
IS  - 11
VL  - 1822
DO  - 10.1016/j.bbadis.2012.08.006.
SP  - 1826
EP  - 1836
ER  - 

@article{
author = "Arsikin-Csordas, Katarina and Kravić-Stevović, Tamara and Jovanović, Maja and Ristić, Biljana and Tovilović-Kovačević, Gordana and Zogović, Nevena and Bumbaširević, Vladimir and Trajković, Vladimir and Harhaji-Trajković, Ljubica",
year = "2012",
abstract = "The role of the main intracellular energy sensor adenosine monophosphate (AMP)-activated protein kinase (AMPK) in the induction of autophagic response and cell death was investigated in SH-SY5Y human neuroblastoma cells exposed to the dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA). The induction of autophagy in SH-SY5Y cells was demonstrated by acridine orange staining of intracellular acidic vesicles, the presence of autophagosome- and autophagolysosome-like vesicles confirmed by transmission electron microscopy, as well as by microtubule-associated protein 1 light-chain 3 (LC3) conversion and p62 degradation detected by immunoblotting. 6-OHDA induced phosphorylation of AMPK and its target Raptor, followed by the dephosphorylation of the major autophagy inhibitor mammalian target of rapamycin (mTOR) and its substrate p70S6 kinase (S6K). 6-OHDA treatment failed to suppress mTOR/S6K phosphorylation and to increase LC3 conversion, p62 degradation and cytoplasmatic acidification in neuroblastoma cells in which AMPK expression was downregulated by RNA interference. Transfection of SH-SY5Y cells with AMPK or LC3β shRNA, as well as treatment with pharmacological autophagy inhibitors suppressed, while mTOR inhibitor rapamycin potentiated 6-OHDA-induced oxidative stress and apoptotic cell death. 6-OHDA induced phosphorylation of p38 mitogen-activated protein (MAP) kinase in an AMPK-dependent manner, and pharmacological inhibition of p38 MAP kinase reduced neurotoxicity, but not AMPK activation and autophagy triggered by 6-OHDA. Finally, the antioxidant N-acetyl cysteine antagonized 6-OHDA-induced activation of AMPK, p38 and autophagy. These data suggest that oxidative stress-mediated AMPK/mTOR-dependent autophagy and AMPK/p38-dependent apoptosis could be valid therapeutic targets for neuroprotection.",
publisher = "Amsterdam: Elsevier",
journal = "Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease",
title = "Autophagy-dependent and -independent involvement of AMP-activated protein kinase in 6-hydroxydopamine toxicity to SH-SY5Y neuroblastoma cells",
number = "11",
volume = "1822",
doi = "10.1016/j.bbadis.2012.08.006.",
pages = "1826-1836"
}

Arsikin-Csordas, K., Kravić-Stevović, T., Jovanović, M., Ristić, B., Tovilović-Kovačević, G., Zogović, N., Bumbaširević, V., Trajković, V.,& Harhaji-Trajković, L.. (2012). Autophagy-dependent and -independent involvement of AMP-activated protein kinase in 6-hydroxydopamine toxicity to SH-SY5Y neuroblastoma cells. in Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
Amsterdam: Elsevier., 1822(11), 1826-1836.
https://doi.org/10.1016/j.bbadis.2012.08.006.

Arsikin-Csordas K, Kravić-Stevović T, Jovanović M, Ristić B, Tovilović-Kovačević G, Zogović N, Bumbaširević V, Trajković V, Harhaji-Trajković L. Autophagy-dependent and -independent involvement of AMP-activated protein kinase in 6-hydroxydopamine toxicity to SH-SY5Y neuroblastoma cells. in Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 2012;1822(11):1826-1836.
doi:10.1016/j.bbadis.2012.08.006. .

Arsikin-Csordas, Katarina, Kravić-Stevović, Tamara, Jovanović, Maja, Ristić, Biljana, Tovilović-Kovačević, Gordana, Zogović, Nevena, Bumbaširević, Vladimir, Trajković, Vladimir, Harhaji-Trajković, Ljubica, "Autophagy-dependent and -independent involvement of AMP-activated protein kinase in 6-hydroxydopamine toxicity to SH-SY5Y neuroblastoma cells" in Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1822, no. 11 (2012):1826-1836,
https://doi.org/10.1016/j.bbadis.2012.08.006. . .

TY  - JOUR
AU  - Harhaji-Trajković, Ljubica
AU  - Popadić, Dušan
AU  - Miljković, Đorđe
AU  - Stojanović, Ivana D.
AU  - Isaković, Aleksandra
AU  - Trajković, Vladimir
PY  - 2005
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6015
AB  - The influence of environmental pH on the production of tumoricidal free radical nitric oxide (NO) was investigated in mouse fibrosarcoma L929 and rat glioma C6 cell lines. A combination of IFN-gamma and IL-1 induced a significant NO release and subsequent reduction of cell viability in tumor cell lines. Acidification of cell culture medium reduced tumor cell NO production in a pH-dependent manner. While the inhibitory effect of acidosis on NO production in C6 cells was associated with a further decrease in cell viability, it completely rescued L929 cells from NO-dependent apoptotic and necrotic death. Acidic pH diminished IFN-gamma+ IL-1-induced expression of inducible NO synthase (iNOS) mRNA and protein, and abolished the activation of iNOS transcription factor IRF-1 in L929 cells. Moreover, extracellular acidosis significantly impaired cytokine-induced phosphorylation of MAP kinase p44/42 (ERK1/2) and subsequent expression of transcription factor c-Fos in L929 cells. Finally, mild acidosis (pH 6.8) augmented, while severe acidosis (pH 6.0) reduced, IFN-gamma-induced iNOS activation/NO release and NO-dependent anticancer activity of rat and mouse macrophages. Taken together, our findings indicate that modulation of macrophage and tumor cell iNOS by an acidic microenvironment might influence the progression of NO-sensitive solid tumors.
PB  - Elsevier Inc.
T2  - Free Radical Biology and Medicine
T1  - Acidosis affects tumor cell survival through modulation of nitric oxide release
IS  - 2
VL  - 40
DO  - 10.1016/j.freeradbiomed.2005.08.027
SP  - 226
EP  - 235
ER  - 

@article{
author = "Harhaji-Trajković, Ljubica and Popadić, Dušan and Miljković, Đorđe and Stojanović, Ivana D. and Isaković, Aleksandra and Trajković, Vladimir",
year = "2005",
abstract = "The influence of environmental pH on the production of tumoricidal free radical nitric oxide (NO) was investigated in mouse fibrosarcoma L929 and rat glioma C6 cell lines. A combination of IFN-gamma and IL-1 induced a significant NO release and subsequent reduction of cell viability in tumor cell lines. Acidification of cell culture medium reduced tumor cell NO production in a pH-dependent manner. While the inhibitory effect of acidosis on NO production in C6 cells was associated with a further decrease in cell viability, it completely rescued L929 cells from NO-dependent apoptotic and necrotic death. Acidic pH diminished IFN-gamma+ IL-1-induced expression of inducible NO synthase (iNOS) mRNA and protein, and abolished the activation of iNOS transcription factor IRF-1 in L929 cells. Moreover, extracellular acidosis significantly impaired cytokine-induced phosphorylation of MAP kinase p44/42 (ERK1/2) and subsequent expression of transcription factor c-Fos in L929 cells. Finally, mild acidosis (pH 6.8) augmented, while severe acidosis (pH 6.0) reduced, IFN-gamma-induced iNOS activation/NO release and NO-dependent anticancer activity of rat and mouse macrophages. Taken together, our findings indicate that modulation of macrophage and tumor cell iNOS by an acidic microenvironment might influence the progression of NO-sensitive solid tumors.",
publisher = "Elsevier Inc.",
journal = "Free Radical Biology and Medicine",
title = "Acidosis affects tumor cell survival through modulation of nitric oxide release",
number = "2",
volume = "40",
doi = "10.1016/j.freeradbiomed.2005.08.027",
pages = "226-235"
}

Harhaji-Trajković, L., Popadić, D., Miljković, Đ., Stojanović, I. D., Isaković, A.,& Trajković, V.. (2005). Acidosis affects tumor cell survival through modulation of nitric oxide release. in Free Radical Biology and Medicine
Elsevier Inc.., 40(2), 226-235.
https://doi.org/10.1016/j.freeradbiomed.2005.08.027

Harhaji-Trajković L, Popadić D, Miljković Đ, Stojanović ID, Isaković A, Trajković V. Acidosis affects tumor cell survival through modulation of nitric oxide release. in Free Radical Biology and Medicine. 2005;40(2):226-235.
doi:10.1016/j.freeradbiomed.2005.08.027 .

Harhaji-Trajković, Ljubica, Popadić, Dušan, Miljković, Đorđe, Stojanović, Ivana D., Isaković, Aleksandra, Trajković, Vladimir, "Acidosis affects tumor cell survival through modulation of nitric oxide release" in Free Radical Biology and Medicine, 40, no. 2 (2005):226-235,
https://doi.org/10.1016/j.freeradbiomed.2005.08.027 . .

TY  - JOUR
AU  - Miljković, Đorđe
AU  - Trajković, Vladimir
PY  - 2004
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6010
AB  - Interleukin-17 (IL-17) is a proinflammatory T cell cytokine presumably involved in physiological responses to infection, but also in immunopathology of autoimmune disorders such as rheumatoid arthritis. The proinflammatory action of IL-17 depends considerably on its ability to trigger the expression of inducible nitric oxide (NO) synthase (iNOS), an enzyme responsible for the generation of cytotoxic and immunoregulatory free radical NO. Here we discuss the role of IL-17 in the cytokine network controlling iNOS expression, and analyze signaling pathways employed by IL-17 for the initiation of iNOS gene transcription. We also propose biological consequences of IL-17-mediated NO release that could be relevant for the mechanisms or therapy of autoimmune and inflammatory disorders.
PB  - Elsevier
T2  - Cytokine and Growth Factor Reviews
T1  - Inducible nitric oxide synthase activation by interleukin-17
IS  - 1
VL  - 15
DO  - 10.1016/j.cytogfr.2003.10.003
SP  - 21
EP  - 32
ER  - 

@article{
author = "Miljković, Đorđe and Trajković, Vladimir",
year = "2004",
abstract = "Interleukin-17 (IL-17) is a proinflammatory T cell cytokine presumably involved in physiological responses to infection, but also in immunopathology of autoimmune disorders such as rheumatoid arthritis. The proinflammatory action of IL-17 depends considerably on its ability to trigger the expression of inducible nitric oxide (NO) synthase (iNOS), an enzyme responsible for the generation of cytotoxic and immunoregulatory free radical NO. Here we discuss the role of IL-17 in the cytokine network controlling iNOS expression, and analyze signaling pathways employed by IL-17 for the initiation of iNOS gene transcription. We also propose biological consequences of IL-17-mediated NO release that could be relevant for the mechanisms or therapy of autoimmune and inflammatory disorders.",
publisher = "Elsevier",
journal = "Cytokine and Growth Factor Reviews",
title = "Inducible nitric oxide synthase activation by interleukin-17",
number = "1",
volume = "15",
doi = "10.1016/j.cytogfr.2003.10.003",
pages = "21-32"
}

Miljković, Đ.,& Trajković, V.. (2004). Inducible nitric oxide synthase activation by interleukin-17. in Cytokine and Growth Factor Reviews
Elsevier., 15(1), 21-32.
https://doi.org/10.1016/j.cytogfr.2003.10.003

Miljković Đ, Trajković V. Inducible nitric oxide synthase activation by interleukin-17. in Cytokine and Growth Factor Reviews. 2004;15(1):21-32.
doi:10.1016/j.cytogfr.2003.10.003 .

Miljković, Đorđe, Trajković, Vladimir, "Inducible nitric oxide synthase activation by interleukin-17" in Cytokine and Growth Factor Reviews, 15, no. 1 (2004):21-32,
https://doi.org/10.1016/j.cytogfr.2003.10.003 . .

TY  - JOUR
AU  - Trajković, Vladimir
AU  - Marković, Miloš
AU  - Samardzić, Tatjana
AU  - Miljković, Đorđe
AU  - Popadić, Dušan
AU  - Mostarica Stojković, Marija
PY  - 2001
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5996
AB  - Because the neurotoxic effects of the antifungal drug amphotericin B
(AMB) closely resemble those ascribed to the highly reactive gaseous free radical nitric
oxide (NO), we investigated the effect of AMB on NO production in rodent astrocytes.
AMB caused a dose-dependent increase of NO generation in interferon-g (IFN-g)-stimulated rat and mouse astrocytes, as well as in IFN-g 1 tumor necrosis factor-a (TNFa)-activated rat astrocytoma cell line C6. Treatment of rat astrocytes with AMB markedly potentiated IFN-g-triggered expression of mRNA for iNOS, but not for its
transcription factor IRF-1. The activation of transcription factor NF-kB was apparently
required for AMB-induced iNOS mRNA expression, as the latter was abolished by
NF-kB inhibitors: pyrrolidine dithiocarbamate and MG132. AMB-mediated enhancement of astrocyte NO production was partly dependent on endogenous IL-1, as shown by
partial inhibition of AMB effect with IL-1 receptor antagonist. IFN-g 1 AMB treatment
led to reduction of astrocyte mitochondrial respiration (measured by MTT assay) that
has been completely reverted by selective iNOS inhibitor aminoguanidine. AMB toxicity
toward IFN-g-stimulated astrocytes was dependent on both AMB and NO action, since
AMB and NO-releasing substance SNP synergized in inducing astrocyte mitochondrial
dysfunction. These results suggest that the enhancement of cytokine-induced iNOS
activation in astrocytes and the subsequent release of high amounts of NO might be at
least partly responsible for AMB neurotoxicity.
PB  - Hoboken: Wiley
T2  - Glia
T1  - Amphotericin B Potentiates the Activation of Inducible Nitric Oxide Synthase and Causes Nitric OxideDependent Mitochondrial Dysfunction in Cytokine-Treated Rodent Astrocytes
IS  - 3
VL  - 35
DO  - 10.1002/glia.1083
SP  - 180
EP  - 188
ER  - 

@article{
author = "Trajković, Vladimir and Marković, Miloš and Samardzić, Tatjana and Miljković, Đorđe and Popadić, Dušan and Mostarica Stojković, Marija",
year = "2001",
abstract = "Because the neurotoxic effects of the antifungal drug amphotericin B
(AMB) closely resemble those ascribed to the highly reactive gaseous free radical nitric
oxide (NO), we investigated the effect of AMB on NO production in rodent astrocytes.
AMB caused a dose-dependent increase of NO generation in interferon-g (IFN-g)-stimulated rat and mouse astrocytes, as well as in IFN-g 1 tumor necrosis factor-a (TNFa)-activated rat astrocytoma cell line C6. Treatment of rat astrocytes with AMB markedly potentiated IFN-g-triggered expression of mRNA for iNOS, but not for its
transcription factor IRF-1. The activation of transcription factor NF-kB was apparently
required for AMB-induced iNOS mRNA expression, as the latter was abolished by
NF-kB inhibitors: pyrrolidine dithiocarbamate and MG132. AMB-mediated enhancement of astrocyte NO production was partly dependent on endogenous IL-1, as shown by
partial inhibition of AMB effect with IL-1 receptor antagonist. IFN-g 1 AMB treatment
led to reduction of astrocyte mitochondrial respiration (measured by MTT assay) that
has been completely reverted by selective iNOS inhibitor aminoguanidine. AMB toxicity
toward IFN-g-stimulated astrocytes was dependent on both AMB and NO action, since
AMB and NO-releasing substance SNP synergized in inducing astrocyte mitochondrial
dysfunction. These results suggest that the enhancement of cytokine-induced iNOS
activation in astrocytes and the subsequent release of high amounts of NO might be at
least partly responsible for AMB neurotoxicity.",
publisher = "Hoboken: Wiley",
journal = "Glia",
title = "Amphotericin B Potentiates the Activation of Inducible Nitric Oxide Synthase and Causes Nitric OxideDependent Mitochondrial Dysfunction in Cytokine-Treated Rodent Astrocytes",
number = "3",
volume = "35",
doi = "10.1002/glia.1083",
pages = "180-188"
}

Trajković, V., Marković, M., Samardzić, T., Miljković, Đ., Popadić, D.,& Mostarica Stojković, M.. (2001). Amphotericin B Potentiates the Activation of Inducible Nitric Oxide Synthase and Causes Nitric OxideDependent Mitochondrial Dysfunction in Cytokine-Treated Rodent Astrocytes. in Glia
Hoboken: Wiley., 35(3), 180-188.
https://doi.org/10.1002/glia.1083

Trajković V, Marković M, Samardzić T, Miljković Đ, Popadić D, Mostarica Stojković M. Amphotericin B Potentiates the Activation of Inducible Nitric Oxide Synthase and Causes Nitric OxideDependent Mitochondrial Dysfunction in Cytokine-Treated Rodent Astrocytes. in Glia. 2001;35(3):180-188.
doi:10.1002/glia.1083 .

Trajković, Vladimir, Marković, Miloš, Samardzić, Tatjana, Miljković, Đorđe, Popadić, Dušan, Mostarica Stojković, Marija, "Amphotericin B Potentiates the Activation of Inducible Nitric Oxide Synthase and Causes Nitric OxideDependent Mitochondrial Dysfunction in Cytokine-Treated Rodent Astrocytes" in Glia, 35, no. 3 (2001):180-188,
https://doi.org/10.1002/glia.1083 . .