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

Quanguang Zhang, Hui Tian, Xinzhen Fu, Guangyi Zhang

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)37-45
Number of pages9
JournalLife sciences
Volume74
Issue number1
DOIs
StatePublished - Nov 21 2003
Externally publishedYes

Fingerprint

MAP Kinase Kinase 7
Hippocampal CA1 Region
Brain Ischemia
Rats
Chemical activation
JNK Mitogen-Activated Protein Kinases
Ischemia
Antioxidants
Phosphorylation
MAP Kinase Signaling System
Scavenging
Acetylcysteine
Cell death
Immunoprecipitation
Sulfhydryl Compounds
Protein Kinases
Free Radicals
Signal Transduction
Cell Death
Phosphotransferases

Keywords

  • Cerebral ischemia
  • Hippocampus
  • Mitogen-activated protein kinase kinase 7 (MKK7)
  • N-acetylcysteine (NAC)
  • Phosphorylation
  • Rat

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Delayed activation and regulation of MKK7 in hippocampal CA1 region following global cerebral ischemia in rats. / Zhang, Quanguang; Tian, Hui; Fu, Xinzhen; Zhang, Guangyi.

In: Life sciences, Vol. 74, No. 1, 21.11.2003, p. 37-45.

Research output: Contribution to journalArticle

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