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The role of MMP-9 in integrin-mediated hippocampal cell death after pilocarpine-induced status epilepticus

Authors
 Gyung W. Kim  ;  Hyun-Jeong Kim  ;  Kyoung-Joo Cho  ;  Hyun-Woo Kim  ;  Yang-Je Cho  ;  Byung I. Lee 
Citation
 Neurobiology of Disease, Vol.36(1) : 169-180, 2009 
Journal Title
 Neurobiology of Disease 
ISSN
 0969-9961 
Issue Date
2009
Abstract
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 beta1-integrin levels decreased on day 3 after SE. beta1-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, beta1-integrin degradation, the reduction of ILK activity and Akt phosphorylation, and subsequent hippocampal damage after SE. However, co-treatment with anti-beta1-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
Full Text
http://www.sciencedirect.com/science/article/pii/S096999610900179X
DOI
10.1016/j.nbd.2009.07.008
Appears in Collections:
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Gyung Whan(김경환) ORCID logo https://orcid.org/0000-0001-7053-4372
Kim, Hyun Woo(김현우)
Kim, Hyun Jeong(김현정)
Lee, Byung In(이병인)
Cho, Kyuong Joo(조경주)
Cho, Yang Je(조양제)
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/104287
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