期刊
FREE RADICAL RESEARCH
卷 52, 期 4, 页码 491-506出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/10715762.2018.1449210
关键词
Nitric oxide; nitrosative stress; cellular redox status; autophagy; apoptosis; CML-K562 cell line; TAp73 alpha
资金
- DBT, government offices of India [BT/PR12551/BRB/10/02/2009]
- UGC, government offices of India [UGC/787/JRF]
- CSIR, government offices of India [09/028(0945)/2015-EMR-I]
- DST-PURSE programme, government offices of India
The biological outcome of nitric oxide (NO) and reactive nitrogen species (RNS) in regulating pro survival and pro death autophagic pathways still demand further investigation. In the present study, we investigated the effect of nitrosative stress in K562 cells using NO donor compound DETA-NONOate, peroxynitrite, and SIN-1. Exposure to NO, peroxynitrite, and SIN-1 caused decrease in K562 cell survival. NO induced autophagy but not apoptosis or necrosis in K562 cells. In contrast, peroxynitrite and SIN-1 treatment induced apoptosis in K562 cells. Surprisingly, inhibition of autophagic response using 3-methyladenine led to the induction of apoptosis in K562 cells. Increase in 5'adenosine monophosphate-activated protein kinase (AMPK) phosphorylation was only observed in the presence of NO donor indicated that AMPK was crucial to induce autophagy in K562 cells. We for the first time discovered a novel role of p73 in autophagy induction under nitrosative stress in K562 cells. TAp73 alpha was only induced upon exposure to NO but not in the presence of peroxynitrite. Reduced glutathione (GSH)/oxidised glutathione (GSSG) ratio remained unaltered upon NO exposure. Our data suggest a complex network of interaction and cross regulations between NO and p73. These data open a new path for therapies based on the abilities of RNS to induce autophagy-mediated cell death.
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