Journal
NEUROBIOLOGY OF DISEASE
Volume 36, Issue 1, Pages 169-180Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2009.07.008
Keywords
Matrix metalloproteinase; Integrins; Pilocarpine; Status epilepticus
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Funding
- Korea Science and Engineering Foundation [KOSEF-2-0709-0008]
- Yonsei University Research Fund [6-2007-0118]
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Recent studies demonstrate that matrix metalloproteinase-9 (MMP-9) is closely involved in the pathogenesis of epilepsy. This study investigated the role of MMP-9 in hippocampal cell death after pilocarpine-induced status epilepticus (SE). We showed that MMP-9 expression and activity significantly increased and beta 1-integrin levels decreased on day 3 after SE. beta 1-integrin degradation was also observed in hippocampal ex vivo extracts incubated with recombinant active MMP-9. Treatment with a selective MMP-9 inhibitor attenuated MMP-9 up-regulation, beta 1-integrin degradation, the reduction of ILK activity and Akt phosphorylation, and subsequent hippocampal damage after SE. However, co-treatment with anti-beta 1-integrin antibody almost completely blocked the protective effects of the MMP-9 inhibitor on both integrin-mediated survival signaling and hippocampal cell death. Our study demonstrates that MMP-9 induces apoptotic hippocampal cell death by interrupting integrin-mediated survival signaling after SE and suggests that MMP-9 may be a promising target for a neuroprotective approach to preventing seizure-induced hippocampal damage. (C) 2009 Elsevier Inc. All rights reserved.
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