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

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 stre...

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Bibliographic Details
Published in:Life sciences (1973) 2003-11, Vol.74 (1), p.37-45
Main Authors: Zhang, Quanguang, Tian, Hui, Fu, Xinzhen, Zhang, Guangyi
Format: Article
Language:English
Subjects:
Acetylcysteine - pharmacology
Animals
Brain Ischemia - enzymology
Cerebral ischemia
Enzyme Activation
Hippocampus
Hippocampus - enzymology
Male
MAP Kinase Kinase 7
Mitogen-activated protein kinase kinase 7 (MKK7)
Mitogen-Activated Protein Kinase Kinases - metabolism
N-acetylcysteine (NAC)
Phosphorylation
Rat
Rats
Rats, Sprague-Dawley
Signal Transduction
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Summary: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.
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2003.06.025