Time-dependence of cardiomyocyte differentiation disturbed by peroxi-some proliferator-activated receptor a inhibitor GW6471 in murine embryonic stem cells in vitro
Time-dependence of cardiomyocyte differentiation disturbed by peroxi-some proliferator-activated receptor a inhibitor GW6471 in murine embryonic stem cells in vitro作者机构：Institute of Pharmacology and Toxicology and Biochemical Pharmaceutics College of Pharmaceutical Sciences Zhejiang University Hangzhou China
出 版 物：《Acta Pharmacologica Sinica》 (中国药理学报(英文版))
年 卷 期：2007年第28卷第5期
页 面：634-642页
核心收录：
学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
基 金：the National Natural Sciences Foundation of China(№ 30171121,30472112,30672564) the Key Grant of the Chinese Ministry of Education(№ 03088) the International Joint Key Grant of Zhejiang Province(№ 2003C24005)
主 题：peroxisome proliferator-activated receptor α p38 MAPK embryonic stem cells cardiomyocytes differentiation
摘 要：Aim:To investigate the possible roles of peroxisome proliferator-activated recep-tor α(PPARα) and the signal pathway regulating the transcription of PPARα inthe cardiomyocyte differentiation course of murine embryonic stem (ES) cells ***:The expression of PPARα during cardiomyocyte differentiationwas analyzed using both Western blotting and *** genes and sarcomeric proteins were evaluated when embryoid bodieswere challenged with PPARα specific inhibitor GW6471 at different time *** phosphorylation of p38 mitogen-activated protein kinase (MAPK) was stud-ied in the differentiation process,and its specific inhibitor SB203580 was em-ployed to study the function of p38 MAPK on cardiac differentiation and theexpression of PPARα.Results:The expression of PPARα was observed to be ata low level in undifferentiated ES cells and markedly induced with the appearanceof beating *** inhibition of PPARα by its specific inhibitor GW6471(1×10-5mol/L) significantly prevented cardiomyocyte differentiation and resultedin the reduced expression of cardiac sarcomeric proteins (ie α-actinin,troponin-T)and specific genes (ie α-MHC,MLC2v) in a time-dependent *** the differ-entiation course,p-p38 MAPK was maintained at a high level from d 3 followed bya decrease from d *** inhibition of the p38 MAPK pathway by SB203580between d 3 and d 7 efficiently prevented cardiomyocyte differentiation and re-suited in the capture of the upregulation of PPARα.Conclusion:Taken together,these results showed a close association between PPARα and cardiomyocytedifferentiation in vitro,and p38 MAPK was partly responsible for the regulationof PPARα.
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