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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2009-9-11
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pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1095-953X
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
36
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
169-80
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pubmed:meshHeading |
pubmed-meshheading:19631748-Analysis of Variance,
pubmed-meshheading:19631748-Animals,
pubmed-meshheading:19631748-Antibodies,
pubmed-meshheading:19631748-Antigens, CD29,
pubmed-meshheading:19631748-Caspase 3,
pubmed-meshheading:19631748-Cell Death,
pubmed-meshheading:19631748-Disease Models, Animal,
pubmed-meshheading:19631748-Dose-Response Relationship, Drug,
pubmed-meshheading:19631748-Enzyme Inhibitors,
pubmed-meshheading:19631748-Hippocampus,
pubmed-meshheading:19631748-In Situ Nick-End Labeling,
pubmed-meshheading:19631748-Male,
pubmed-meshheading:19631748-Matrix Metalloproteinase 2,
pubmed-meshheading:19631748-Matrix Metalloproteinase 9,
pubmed-meshheading:19631748-Mice,
pubmed-meshheading:19631748-Mice, Inbred C57BL,
pubmed-meshheading:19631748-Phosphopyruvate Hydratase,
pubmed-meshheading:19631748-Propidium,
pubmed-meshheading:19631748-Signal Transduction,
pubmed-meshheading:19631748-Statistics as Topic,
pubmed-meshheading:19631748-Status Epilepticus,
pubmed-meshheading:19631748-Time Factors,
pubmed-meshheading:19631748-Up-Regulation
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pubmed:year |
2009
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pubmed:articleTitle |
The role of MMP-9 in integrin-mediated hippocampal cell death after pilocarpine-induced status epilepticus.
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pubmed:affiliation |
Department of Neurology and Brain Korea 21 Project for Medical Science, College of Medicine, Yonsei University, 134, Sinchon-dong, Seodaemun-gu, Seoul 120-752, Republic of Korea.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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