کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6261580 | 1613232 | 2016 | 6 صفحه PDF | دانلود رایگان |
- MKK4 could be S-nitrosylated in rats.
- S-nitrosylation and phosphorylation of MKK4 are mediated by nNOS and NMDAR.
- Treatment with drugs that attenuate cerebral I/R-induced MKK4 S-nitrosylation.
S-nitrosylation, the nitric oxide-derived post-translational modification of proteins, plays critical roles in various physiological and pathological functions. In this present study, a rat model of cerebral ischemia and reperfusion by four-vessel occlusion was generated to assess MKK4 S-nitrosylation. Immunoprecipitation and immunoblotting were performed to evaluate MKK4 S-nitrosylation and phosphorylation. Neuronal loss was observed using histological detection. These results indicated that endogenous NO promoted the S-nitrosylation of MKK4. However, application of the exogenous NO donor S-nitrosoglutathione (GNSO), an inhibitor of the neuronal nitric oxide synthase 7-nitroindazole (7-NI), and the N-methyl-d-aspartate receptor (NMDAR) antagonist MK801 diminished I/R-induced S-nitrosylation and phosphorylation. These compounds also markedly decreased cerebral I/R-induced degeneration and death of neurons in hippocampal CA1 region in rats. Taken together, we demonstrated for the first time, that cerebral ischemia/reperfusion can induce S-nitrosylation of MKK4. We also found that inhibiting S-nitrosylation and activation of MKK4 resulted in marked decreases in neuronal degeneration and apoptosis, potentially via NMDAR-mediated mechanisms. These findings may lead to a new field of inquiry to investigate the underlying pathogenesis of stoke and the development of novel treatment strategies.
Journal: Brain Research Bulletin - Volume 124, June 2016, Pages 123-128