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Open Access Highly Accessed Research article

PI3K/Akt-independent negative regulation of JNK signaling by MKP-7 after cerebral ischemia in rat hippocampus

JianXi Zhu12, Wei Shen3, Li Gao3, Hao Gu3, ShuTong Shen4, Yi Wang12, HuiWen Wu4 and Jun Guo124*

Author affiliations

1 Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, 210029, People’s Republic of China

2 Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, 210029, People’s Republic of China

3 Department of Neurology, Brain Hospital Affiliated to Nanjing Medical University, Nanjing, 210029, China

4 Laboratory Center for Basic Medical Sciences, Nanjing medical university Nanjing, Nanjing, 210029, People’s Republic of China

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Citation and License

BMC Neuroscience 2013, 14:1  doi:10.1186/1471-2202-14-1

Published: 2 January 2013

Abstract

Background

The inactivation of c-Jun N-terminal kinase (JNK) is associated with anti-apoptotic and anti-inflammatory effects in cerebral ischemia, which can be induced by an imbalance between upstream phosphatases and kinases.

Result

Mitogen-activated protein kinase phosphatase 7 (MKP-7) was upregulated significantly at 4 h of reperfusion postischemia in rat hippocampi. By administration of cycloheximide or siRNA against mitogen-activated protein kinase phosphatase 7 (MKP-7) in a rat model of ischemia/reperfusion, an obvious enhancement of JNK activity was observed in 4 h of reperfusion following ischemia, suggesting MKP-7 was involved in JNK inactivation after ischemia. The subcellular localization of MKP-7 altered after ischemia, and the inhibition of MKP-7 nuclear export by Leptomycin B up-regulated JNK activity. Although PI3K/Akt inhibition could block downregulation of JNK activity through SEK1 and MKK-7 activation, PI3K/Akt activity was not associated with the regulation of JNK by MKP-7.

Conclusions

MKP-7, independently of PI3K/Akt pathway, played a key role in downregulation of JNK activity after ischemia in the rat hippocampus, and the export of MKP-7 from the nucleus was involved in downregulation of cytoplasmic JNK activity in response to ischemic stimuli.

Keywords:
Cerebral ischemia; JNK; PI3K/Akt; MKP-7