title: 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.
  
  
  CONCLUSIONS
  JNK1/2 activation is associated with endogenous NO in response to ischemic insult.
authors.affiliation: Department of Neurosurgery, Affiliated Hospital, Weifang Medical University, Weifang, Shandong 261053, China.
authors.forename: Xian-Wei
authors.initials: XW
authors.lastname: Zeng
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Pan
authors.forename: Tai-Ling
authors.initials: TL
authors.lastname: Ji
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Xiao-Qiang
authors.initials: XQ
authors.lastname: Wang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002545:Brain Ischemia / Q000201:enzymology*; D004791:Enzyme Inhibitors; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism*; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004791:Enzyme Inhibitors; D007191:Indazoles; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D048056:Mitogen-Activated Protein Kinase 9; D048055:Mitogen-Activated Protein Kinase 8; C080122:7-nitroindazole