TY  - JOUR
AU  - Krunić, Matija
AU  - Ristić, Biljana
AU  - Bošnjak, Mihajlo
AU  - Paunović, Verica
AU  - Tovilović-Kovačević, Gordana
AU  - Zagović, Nevena
AU  - Mirčić, Aleksandar
AU  - Marković, Zoran
AU  - Todorović Marković, Biljana
AU  - Jovanović, Svetlana
AU  - Kleut, Duška
AU  - Mojović, Miloš
AU  - Nakarada, Đura
AU  - Marković, Olivera S.
AU  - Vuković, Irena
AU  - Harhaji-Trajković, Ljubica
AU  - Trajković, Vladimir
PY  - 2021
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/5467
AB  - We investigated the ability of graphene quantum dot (GQD) nanoparticles to protect SH-SY5Y human neuro blastoma cells from oxidative/nitrosative stress induced by iron-nitrosyl complex sodium nitroprusside (SNP). 
GQD reduced SNP cytotoxicity by preventing mitochondrial depolarization, caspase-2 activation, and subsequent 
apoptotic death. Although GQD diminished the levels of nitric oxide (NO) in SNP-exposed cells, NO scavengers 
displayed only a slight protective effect, suggesting that NO quenching was not the main protective mechanism of 
GQD. GQD also reduced SNP-triggered increase in the intracellular levels of hydroxyl radical (
•
OH), superoxide 
anion (O2
•− ), and lipid peroxidation. Nonselective antioxidants, •
OH scavenging, and iron chelators, but not 
superoxide dismutase, mimicked GQD cytoprotective activity, indicating that GQD protect cells by neutralizing •
OH generated in the presence of SNP-released iron. Cellular internalization of GQD was required for optimal 
protection, since a removal of extracellular GQD by extensive washing only partly diminished their protective 
effect. Moreover, GQD cooperated with SNP to induce autophagy, as confirmed by the inhibition of autophagy limiting Akt/PRAS40/mTOR signaling and increase in autophagy gene transcription, protein levels of proauto phagic beclin-1 and LC3-II, formation of autophagic vesicles, and degradation of autophagic target p62. The 
antioxidant activity of GQD was not involved in autophagy induction, as antioxidants N-acetylcysteine and 
dimethyl sulfoxide failed to stimulate autophagy in SNP-exposed cells. Pharmacological inhibitors of early 
(wortmannin, 3-methyladenine) or late stages of autophagy (NH4Cl) efficiently reduced the protective effect of 
GQD. Therefore, the ability of GQD to prevent the in vitro neurotoxicity of SNP depends on both •
OH/NO 
scavenging and induction of cytoprotective autophagy.
PB  - Elsevier
T2  - Free Radical Biology and Medicine
T1  - Graphene quantum dot antioxidant and proautophagic actions protect  SH-SY5Y neuroblastoma cells from oxidative stress-mediated  apoptotic death
VL  - 177
SP  - 167
EP  - 180
DO  - 10.1016/j.freeradbiomed.2021.10.025
ER  - 

@article{
author = "Krunić, Matija and Ristić, Biljana and Bošnjak, Mihajlo and Paunović, Verica and Tovilović-Kovačević, Gordana and Zagović, Nevena and Mirčić, Aleksandar and Marković, Zoran and Todorović Marković, Biljana and Jovanović, Svetlana and Kleut, Duška and Mojović, Miloš and Nakarada, Đura and Marković, Olivera S. and Vuković, Irena and Harhaji-Trajković, Ljubica and Trajković, Vladimir",
year = "2021",
abstract = "We investigated the ability of graphene quantum dot (GQD) nanoparticles to protect SH-SY5Y human neuro blastoma cells from oxidative/nitrosative stress induced by iron-nitrosyl complex sodium nitroprusside (SNP). 
GQD reduced SNP cytotoxicity by preventing mitochondrial depolarization, caspase-2 activation, and subsequent 
apoptotic death. Although GQD diminished the levels of nitric oxide (NO) in SNP-exposed cells, NO scavengers 
displayed only a slight protective effect, suggesting that NO quenching was not the main protective mechanism of 
GQD. GQD also reduced SNP-triggered increase in the intracellular levels of hydroxyl radical (
•
OH), superoxide 
anion (O2
•− ), and lipid peroxidation. Nonselective antioxidants, •
OH scavenging, and iron chelators, but not 
superoxide dismutase, mimicked GQD cytoprotective activity, indicating that GQD protect cells by neutralizing •
OH generated in the presence of SNP-released iron. Cellular internalization of GQD was required for optimal 
protection, since a removal of extracellular GQD by extensive washing only partly diminished their protective 
effect. Moreover, GQD cooperated with SNP to induce autophagy, as confirmed by the inhibition of autophagy limiting Akt/PRAS40/mTOR signaling and increase in autophagy gene transcription, protein levels of proauto phagic beclin-1 and LC3-II, formation of autophagic vesicles, and degradation of autophagic target p62. The 
antioxidant activity of GQD was not involved in autophagy induction, as antioxidants N-acetylcysteine and 
dimethyl sulfoxide failed to stimulate autophagy in SNP-exposed cells. Pharmacological inhibitors of early 
(wortmannin, 3-methyladenine) or late stages of autophagy (NH4Cl) efficiently reduced the protective effect of 
GQD. Therefore, the ability of GQD to prevent the in vitro neurotoxicity of SNP depends on both •
OH/NO 
scavenging and induction of cytoprotective autophagy.",
publisher = "Elsevier",
journal = "Free Radical Biology and Medicine",
title = "Graphene quantum dot antioxidant and proautophagic actions protect  SH-SY5Y neuroblastoma cells from oxidative stress-mediated  apoptotic death",
volume = "177",
pages = "167-180",
doi = "10.1016/j.freeradbiomed.2021.10.025"
}

Krunić, M., Ristić, B., Bošnjak, M., Paunović, V., Tovilović-Kovačević, G., Zagović, N., Mirčić, A., Marković, Z., Todorović Marković, B., Jovanović, S., Kleut, D., Mojović, M., Nakarada, Đ., Marković, O. S., Vuković, I., Harhaji-Trajković, L.,& Trajković, V.. (2021). Graphene quantum dot antioxidant and proautophagic actions protect  SH-SY5Y neuroblastoma cells from oxidative stress-mediated  apoptotic death. in Free Radical Biology and Medicine
Elsevier., 177, 167-180.
https://doi.org/10.1016/j.freeradbiomed.2021.10.025

Krunić M, Ristić B, Bošnjak M, Paunović V, Tovilović-Kovačević G, Zagović N, Mirčić A, Marković Z, Todorović Marković B, Jovanović S, Kleut D, Mojović M, Nakarada Đ, Marković OS, Vuković I, Harhaji-Trajković L, Trajković V. Graphene quantum dot antioxidant and proautophagic actions protect  SH-SY5Y neuroblastoma cells from oxidative stress-mediated  apoptotic death. in Free Radical Biology and Medicine. 2021;177:167-180.
doi:10.1016/j.freeradbiomed.2021.10.025 .

Krunić, Matija, Ristić, Biljana, Bošnjak, Mihajlo, Paunović, Verica, Tovilović-Kovačević, Gordana, Zagović, Nevena, Mirčić, Aleksandar, Marković, Zoran, Todorović Marković, Biljana, Jovanović, Svetlana, Kleut, Duška, Mojović, Miloš, Nakarada, Đura, Marković, Olivera S., Vuković, Irena, Harhaji-Trajković, Ljubica, Trajković, Vladimir, "Graphene quantum dot antioxidant and proautophagic actions protect  SH-SY5Y neuroblastoma cells from oxidative stress-mediated  apoptotic death" in Free Radical Biology and Medicine, 177 (2021):167-180,
https://doi.org/10.1016/j.freeradbiomed.2021.10.025 . .