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Delayed activation and regulation of MKK7 in hippocampal CA1 region following global cerebral ischemia in rats.

Abstract
c-Jun N-terminal protein kinase (JNK) activation and subsequent c-Jun phosphorylation which stimulates its transcriptional activity have been well studied in cerebral ischemia. To determine whether mitogen-activated protein kinase kinase 7 (MKK7) play a role in JNK activation in response to the stress of global cerebral ischemia, we tested the activation of such a kinase by using phospho-Ser and phospho-Thr antibodies. Immunoprecipitation and Western blot analysis revealed that MKK7 was expressed at similar levels in all conditions, whereas phospho-MKK7 was highly augmented from 1 to 5 days and reached its peak at 3 days after 15 min of ischemia. Consistent with the active phase, the interaction of MLK3, ASK1 and phospho-JNK with MKK7 was increased compared with sham control, as shown by coimmunoprecipitation experiments. Moreover, MKK7 activation was markedly reduced by pretreatment of the free radical scavenging thiol antioxidant N-acetylcysteine (NAC). Together with previous studies, the late activation of MKK7 in hippocampal CA1 region may contribute to delayed cell death, and the protective effects of antioxidant against ischemia-induced injury may be partially mediated by the down-regulation of JNK signal pathway.
AuthorsQuanguang Zhang, Hui Tian, Xinzhen Fu, Guangyi Zhang
JournalLife sciences (Life Sci) Vol. 74 Issue 1 Pg. 37-45 (Nov 21 2003) ISSN: 0024-3205 [Print] Netherlands
PMID14575811 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • MAP Kinase Kinase 7
  • Mitogen-Activated Protein Kinase Kinases
  • Acetylcysteine
Topics
  • Acetylcysteine (pharmacology)
  • Animals
  • Brain Ischemia (enzymology)
  • Enzyme Activation
  • Hippocampus (enzymology)
  • MAP Kinase Kinase 7
  • Male
  • Mitogen-Activated Protein Kinase Kinases (metabolism)
  • Phosphorylation
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction

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