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

Neurobiology of Disease

Byung I. Lee¹  Kyoung-Joo Cho²  Hyun-Woo Kim²  Yang-Je Cho²  Hyun-Jeong Kim²  Gyung W. Kim² 

[1] Corresponding author. Department of Neurology, College of Medicine, Yonsei University, 134, Sinchon-dong, Seodaemun-gu, Seoul 120-752, Republic of Korea. Fax: [phone].;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;

关键词: Matrix metalloproteinase;    Integrins;    Pilocarpine;    Status epilepticus;   

DOI  :  

来源: DOAJ

【 摘 要 】

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 β1-integrin levels decreased on day 3 after SE. β1-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, β1-integrin degradation, the reduction of ILK activity and Akt phosphorylation, and subsequent hippocampal damage after SE. However, co-treatment with anti-β1-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.

【 授权许可】

Unknown