Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death
| Autor: | Nevena Zogovic, Duška Kleut, Gordana Tovilovic-Kovacevic, Olivera Markovic, Matija Krunić, Mihajlo Bosnjak, Ljubica Harhaji-Trajkovic, Svetlana Jovanovic, Irena Vuković, Vladimir Trajkovic, Biljana Todorovic-Markovic, Verica Paunovic, Miloš Mojović, Aleksandar Mirčić, Biljana Ristic, Đura Nakarada, Zoran Marković |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Apoptosis
02 engineering and technology medicine.disease_cause Biochemistry Antioxidants Superoxide dismutase Lipid peroxidation Wortmannin Neuroblastoma 03 medical and health sciences chemistry.chemical_compound Cell Line Tumor Physiology (medical) Quantum Dots medicine Neurotoxicity Autophagy Humans Sodium nitroprusside Protein kinase B 030304 developmental biology 0303 health sciences biology Superoxide Graphene quantum dots Nitric oxide 021001 nanoscience & nanotechnology medicine.disease Cell biology Oxidative Stress chemistry Oxidative stress biology.protein Graphite 0210 nano-technology Hydroxyl radical |
| Zdroj: | Free Radical Biology and Medicine |
| Popis: | We investigated the ability of graphene quantum dot (GQD) nanoparticles to protect SH-SY5Y human neuroblastoma 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 autophagylimiting Akt/PRAS40/mTOR signaling and increase in autophagy gene transcription, protein levels of proautophagic 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. This is the peer-reviewed version of the article: Matija Krunić, Biljana Ristić, Mihajlo Bošnjak, Verica Paunović, Gordana Tovilović- Kovacević, Nevena Zogović, Aleksandar Mirčić, Zoran Marković, Biljana Todorović- Marković, Svetlana Jovanović, Duška Kleut, Miloš Mojović, Đura Nakarada, Olivera Marković, Irena Vuković, Ljubica Harhaji-Trajković, Vladimir Trajković, Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death, Free Radical Biology and Medicine, 2021, 177, 167-180, doi: [https://doi.org/10.1016/j.freeradbiomed.2021.10.025] The published version: [https://cer.ihtm.bg.ac.rs/handle/123456789/4812] |
| Databáze: | OpenAIRE |
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