RIP3 S-nitrosylation contributes to cerebral ischemic neuronal injury

Brain Research
Wan-Ying MiaoShu-Qun Hu

Abstract

Cerebral ischemia-reperfusion is associated with NMDA receptor-mediated calcium influx which activates neuronal nitric oxide synthase (nNOS) and consequently induces NO production. NO S-nitrosylates cellular protein and aggravates neuronal injury. Receptor-interacting protein 3 (RIP3) is a sensor molecule regulating cell apoptosis and necrosis. However, the roles of RIP3 in cerebral ischemic injury remain elusive. In this study, we reported that RIP3 could be S-nitrosylated by the exogenous NO donor GSNO in HEK293 cells and the Cys(119) residue was the key nitrosylation site. In addition, we found that cerebral ischemia induced RIP3 S-nitrosylation at different time points of reperfusion, which was coupling with RIP3 phosphorylation (which is associated with its activation) and its interaction with receptor-interacting protein 1 (RIP1), and this process facilitated cerebral ischemic injury. Treatment with NMDA receptor antagonist MK801, or nNOS inhibitor 7NI, diminished RIP3 S-nitrosylation and reduced neuronal damage. Taken together, these data demonstrated that NMDAR-dependent RIP3 S-nitrosylation induced by ischemia facilitated its activation in the early stages of ischemia, blocking this process could reduce the ischemia ne...Continue Reading

References

May 1, 1979·Stroke; a Journal of Cerebral Circulation·W A Pulsinelli, J B Brierley
Jul 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·V L DawsonS H Snyder
Sep 7, 2000·Neuropharmacology·G A RameauE B Ziff
Jul 21, 2001·Cell Death and Differentiation·A Martin-VillalbaP H Krammer
Dec 26, 2001·Science's STKE : Signal Transduction Knowledge Environment·S R Jaffrey, S H Snyder
Mar 9, 2005·Trends in Biochemical Sciences·Etienne Meylan, Jürg Tschopp
Apr 17, 2008·Nature Reviews. Molecular Cell Biology·Alexei Degterev, Junying Yuan
Sep 10, 2009·Nature Reviews. Molecular Cell Biology·Moran BenharJonathan S Stamler
Jun 24, 2010·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Frances J NorthingtonLee J Martin
Nov 30, 2011·The Journal of Biological Chemistry·Shu-Qun HuGuang-Yi Zhang

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Citations

Feb 20, 2019·Frontiers in Neuroscience·Xiu-Yun ZhaoQuan-Hong Ma
Jan 1, 2015·F1000Research·James M Murphy, James E Vince

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