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Neuroprotective effects of KR-62980, a new PPARγ agonist, against chemical ischemia-reperfusion in SK-N-SH cells.
MedLine Citation:
PMID:  21111719     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
PPARγ agonists exert neuroprotective effects against various types of brain injuries. In the present study, we investigated the effects of KR-62980, a new PPARγ agonist, and rosiglitazone on the neuronal cell death induced by chemical ischemia-reperfusion in SK-N-SH cells and their underlying molecular mechanisms. Both agonists inhibited chemical ischemia-reperfusion-induced cell death, and the effects were associated with anti-apoptotic action. KR-62980 and rosiglitazone suppressed NO and ROS formation, and N-acetyl-N-acetoxy-4-chlorobenzenesulfonamide, an NO generator, reversed the protective effects of the agonists on cell viability. In the agonist-induced anti-apoptotic process, PTEN expression was suppressed in parallel with increased Akt and ERK phosphorylation, whereas PD98059 (an ERK inhibitor) or wortmannin (a PI-3K inhibitor) abolished the cell survival by KR-62980 and rosiglitazone. All of the effects of KR-62980 and rosiglitazone appeared to be PPARγ-dependent because the effects were reversed by bisphenol A diglycidyl ether, a PPARγ antagonist, or by PPARγ knockdown. Our results demonstrate that two PPARγ agonists, KR-62980 and rosiglitazone, inhibited chemical ischemia-reperfusion-induced neuronal cell death by PPARγ-mediated anti-apoptotic and anti-oxidant mechanisms related to PTEN suppression and ERK phosphorylation.
Authors:
Ki Young Kim; Hyun Sill Cho; Su Hee Lee; Jin Hee Ahn; Hyae Gyeong Cheon
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Publication Detail:
Type:  Journal Article     Date:  2010-11-25
Journal Detail:
Title:  Brain research     Volume:  1372     ISSN:  1872-6240     ISO Abbreviation:  Brain Res.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  103-14     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier B.V. All rights reserved.
Affiliation:
Bio-Organic Science Division, Korea Research Institute of Chemical Technology, P.O. Box 107, Yuseong-gu, Daejeon, 305-600, Republic of Korea.
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