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.
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Authors | Quanguang Zhang, Hui Tian, Xinzhen Fu, Guangyi Zhang |
Journal | Life sciences
(Life Sci)
Vol. 74
Issue 1
Pg. 37-45
(Nov 21 2003)
ISSN: 0024-3205 [Print] Netherlands |
PMID | 14575811
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- MAP Kinase Kinase 7
- Mitogen-Activated Protein Kinase Kinases
- Acetylcysteine
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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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