Exogenous nitric oxide negatively regulates c-Jun N-terminal kinase activation via inhibiting endogenous NO-induced S-nitrosylation during cerebral ischemia and reperfusion in rat hippocampus.
Nitric oxide (NO), synthesized from l-arginine by NO synthases, is a small endogenous free radical with multiple functions. The c-Jun N-terminal kinase (JNK) signaling pathway plays a critical role in mediating apoptosis in cerebral ischemia and reperfusion. In this study, we found that the NO donor sodium nitroprusside (SNP) can decrease the damage of hippocampal neurons induced by cerebral ischemia and reperfusion. Our current study demonstrates that SNP can suppress the phosphorylation of JNK3 by suppressing the increased S-nitrosylation of JNK3 induced by cerebral ischemia and reperfusion. In contrast, dithiothreitol reversed the effect of SNP on S-nitrosylation of JNK3. Furthermore, the inhibitor of nNOS (7-NI) and the inhibitor of iNOS (AMT) can decrease JNK3 phosphorylation through decreasing S-nitrosylation of JNK3. Our data suggest that endogenous NO synthesized by NO synthases can increase JNK3 phosphorylation by means of S-nitrosylation during global ischemia/reperfusion in rat hippocampus. However, the exogenous NO (SNP) can reverse the effect of endogenous NO by inhibiting S-nitrosylation of JNK3. Together, these results suggest that the exogenous NO may provide a new clue for stroke therapy.
Research Center for Biochemistry and Molecular Biology, The Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical College, Xuzhou, China.
Dong-Sheng
DS
Pei
Yuan-Jian
YJ
Song
Hong-Min
HM
Yu
Wei-Wei
WW
Hu
Yang
Y
Du
Guang-Yi
GY
Zhang
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology
D009569:Nitric Oxide; D048031:JNK Mitogen-Activated Protein Kinases