Neuroprotective activity of GQD against SNP-induced toxicity are mediated by ROS/RNS scavenging and protective autophagy induction
2019
Аутори:
Ristić, BiljanaKrunić, Matija
Bošnjak, Mihajlo
Mirčić, Aleksandar
Tovilović-Kovačević, Gordana
Zogović, Nevena
Paunović, Verica
Trajković, Vladimir
Harhaji-Trajković, Ljubica
Тип документа:
Конференцијски прилог (Објављена верзија)
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© 2019 by the Nordic Autophagy Society
Метаподаци
Приказ свих података о документуАпстракт:
We investigated the ability of nano-sized graphen layers graphen quantum dots (GQD) to protect human neuroblastoma SH-SY5Y cells from toxicity of NO donor sodium nitroprusside (SNP). GQD prevented SNP induced mitochondrial depolarization and caspase dependent apoptosis. GQD partly suppressed neurotoxicity of NO donor DEA-NONOate and reduced SNP induced NO release in cells and cell-free system, suggesting that neuroprotective effects of GQD were partly mediated by their NO-scavanging capacity. However, GQD significantly preserved SH-SY5Y cells from light exhausted SNP, which was unable to produce NO, implying the existence of protective mechanism independent of NO-scavenging. Unspecific antioxidant, as well as hydroxyl radical (.OH) scavengers DMSO, vitamin E and gluthatione mimicked neuroprotective activity of GQD, while GQD diminished concentration of reactive oxygen species (ROS), especially .OH, in cells and cell culture medium, suggesting important role of .OH scavenging in neuroprotective activity of GQD. However ability of GQD to protect SH-SY5Y cells from SNP was not exclusively mediated by their ability to scavenge NO and ROS from medium, since it persisted after washing of GQD preincubated cells. Interestingly, GQD were found to be present in autophagosome-like vacuoles. Both SNP and GQD, and especially their combination, increased intracellular acidity characteristic for presence of autophagosomes, concentration of proautophagic protein beclin-1, while deacreased level of specific substrate of autophagic proteolysis p62. Moreover, SNP and GQD, and above all their combination, increased concentration of autophagosome-associated protein LC3 II in the presence of inhibitor of autophagic proteolysis bafilomycin A1. Finally, autophagy inhibitors 3-methzladenine, wortmannin and NH4Cl prevented neuroprotective ability of GQD, implying that GQD stimulated prosurvival autophagy in SNP treated neurons. Therefore, by demonstrating ability of GQD to protect SH-SY5Y neurons from SNP induced apoptosis by scavenging NO/ROS and stimulation of cytoprotective autophagy, our results suggest that GQD could be valuable candidate for treatment of neurodegenerative disorders.
Кључне речи:
neuroprotection; oxidative/nitrosative stress; autophagy; graphen quantum dotsФинансирање / пројекти:
- Модулација сигналних путева који контролишу интрацелуларни енергетски баланс у терапији тумора и неуро-имуно-ендокриних поремећаја (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41025)
- Улога аутофагије у регулацији смрти туморских ћелија (RS-MESTD-Basic Research (BR or ON)-173053)
У:
- 3rd Nordic Autophagy Society (NAS) Conference; 2019 May 22-24; Utrecht, Nederlands. Nordic Autophagy Society; 2019. p. 40.