Graphene quantum dot antioxidant and proautophagic actions protect SH-SY5Y neuroblastoma cells from oxidative stress-mediated apoptotic death.
2021
Autori:
Krunić, MatijaRistić, Biljana
Bošnjak, Mihajlo
Paunović, Verica
Tovilović-Kovačević, Gordana
Zogović, Nevena
Mirčić, Aleksandar
Marković, Zoran
Todorović-Marković, Biljana
Jovanović, Svetlana
Kleut, Duška
Mojović, Miloš
Nakarada, Đura
Marković, Olivera
Vuković, Irena
Harhaji-Trajković, Ljubica
Trajković, Vladimir
Tip dokumenta:
Članak u časopisu (Objavljena verzija)
,
© 2021 Elsevier Inc.
Metapodaci
Prikaz svih podataka o dokumentuApstrakt:
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 autophagy-limiting 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.
Ključne reči:
Autophagy; Graphene quantum dots; Hydroxyl radical; Neurotoxicity; Nitric oxide; Oxidative stress; Sodium nitroprussideIzvor:
Free Radical Biology and Medicine, 2021, 177, 167-180Finansiranje / projekti:
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200007 (Univerzitet u Beogradu, Institut za biološka istraživanja 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200017 (Univerzitet u Beogradu, Institut za nuklearne nauke Vinča, Beograd-Vinča) (RS-MESTD-inst-2020-200017)
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200026 (Univerzitet u Beogradu, Institut za hemiju, tehnologiju i metalurgiju - IHTM) (RS-MESTD-inst-2020-200026)
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200110 (Univerzitet u Beogradu, Medicinski fakultet) (RS-MESTD-inst-2020-200110)
- Ministarstvo nauke, tehnološkog razvoja i inovacija Republike Srbije, institucionalno finansiranje - 200146 (Univerzitet u Beogradu, Fakultet za fizičku hemiju) (RS-MESTD-inst-2020-200146)
DOI: 10.1016/j.freeradbiomed.2021.10.025
ISSN: 0891-5849
PubMed: 34678419
WoS: 000717740300004
Scopus: 2-s2.0-85117824181
URI
https://linkinghub.elsevier.com/retrieve/pii/S0891584921007760https://radar.ibiss.bg.ac.rs/handle/123456789/4655