کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4323763 1613812 2015 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
RIP3 S-nitrosylation contributes to cerebral ischemic neuronal injury
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
RIP3 S-nitrosylation contributes to cerebral ischemic neuronal injury
چکیده انگلیسی


• The Cys119 residue is the major nitrosylation site of RIP3.
• RIP3 could be S-nitrosylated by NO generated by nNOS during cerebral ischemia–reperfusion, which is mediated by NMDAR.
• Blocking RIP3 S-nitrosylation could reduce ischemic neuronal damage.

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 Cys119 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 neuronal injury.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research - Volume 1627, 19 November 2015, Pages 165–176
نویسندگان
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