Activation of c-Jun N-terminal kinase 1/2 regulated by nitric oxide is associated with neuronal survival in hippocampal neurons in a rat model of ischemia.

Abstract

BACKGROUND:

C-Jun N-terminal kinase (JNK) signaling pathway plays a critical role in cerebral ischemia. Although the mechanistic basis for this activation of JNK1/2 is uncertain, oxidative stress may play a role. The purpose of this study was to investigate whether the activation of JNK1/2 is associated with the production of endogenous nitric oxide (NO).

METHODS:

Ischemia and reperfusion (I/R) was induced by cerebral four-vessel occlusion. Sprague-Dawley (SD) rats were divided into 6 groups: sham group, I/R group, neuronal nitric oxide synthase (nNOS) inhibitor (7-nitroindazole, 7-NI) given group, inducible nitric oxide synthase (iNOS) inhibitor (2-amino-5,6-dihydro-methylthiazine, AMT) given group, sodium chloride control group, and 1% dimethyl sulfoxide (DMSO) control group. The levels of protein expression and phospho-JNK1/2 were detected by Western blotting and the survival hippocampus neurons in CA1 zone were observed by cresyl violet staining.

RESULTS:

The study illustrated two peaks of JNK1/2 activation occurred at 30 minutes and 3 days during reperfusion. 7-NI inhibited JNK1/2 activation during the early reperfusion, whereas AMT preferably attenuated JNK1/2 activation during the later reperfusion. Administration of 7-NI and AMT can decrease I/R-induced neuronal loss in hippocampal CA1 region.

CONCLUSION:

JNK1/2 activation is associated with endogenous NO in response to ischemic insult.

• Authors: Xian-Wei Zeng, Ming-Wei Li, Jing Pan, Tai-Ling Ji, Bin Yang, Bo Zhang, Xiao-Qiang Wang
• Journal: Chinese medical journal (Chin Med J (Engl)) Vol. 124 Issue 20 Pg. 3367-72 (Oct 2011) ISSN: 2542-5641 [Electronic] China
• PMID: 22088537 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Indazoles
• Nitric Oxide
• Nitric Oxide Synthase Type II
• Mitogen-Activated Protein Kinase 9
• Mitogen-Activated Protein Kinase 8
• 7-nitroindazole

Topics

• Animals
• Blotting, Western
• Brain Ischemia (enzymology)
• Enzyme Inhibitors
• Hippocampus (cytology, metabolism)
• Indazoles (pharmacology)
• Male
• Mitogen-Activated Protein Kinase 8 (metabolism)
• Mitogen-Activated Protein Kinase 9 (metabolism)
• Neurons (cytology, metabolism)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type II (antagonists & inhibitors)
• Phosphorylation (drug effects)
• Rats
• Rats, Sprague-Dawley