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

• Published in: Journal of neurochemistry 2008-08, Vol.106 (4), p.1952-1963
• Main Authors: Pei, Dong-Sheng, Song, Yuan-Jian, Yu, Hong-Min, Hu, Wei-Wei, Du, Yang, Zhang, Guang-Yi
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry; Biological and medical sciences; Brain Ischemia - drug therapy; Brain Ischemia - enzymology; Brain Ischemia - physiopathology; Cardiology. Vascular system; cerebral ischemia; c‐Jun N‐terminal kinase; Enzyme Activation - drug effects; Enzyme Activation - physiology; Hippocampus - drug effects; Hippocampus - enzymology; Hippocampus - physiopathology; JNK Mitogen-Activated Protein Kinases - metabolism; Kinases; Male; Medical sciences; mitogen-activated protein kinase; Neurology; Nitric oxide; Nitric Oxide - pharmacology; Nitric Oxide - physiology; Rats; Rats, Sprague-Dawley; Reperfusion Injury - drug therapy; Reperfusion Injury - enzymology; Reperfusion Injury - physiopathology; S-nitrosylation; Signal transduction; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2008.05531.x

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.