title: Activation of peroxisome proliferator-activated receptor-alpha prevents glycogen synthase 3beta phosphorylation and inhibits cardiac hypertrophy.
abstract: Activation of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) has been recently reported to inhibit vascular inflammatory response and prevent cardiac hypertrophy. However, it is unclear how the activation of PPAR-alpha regulates hypertrophic response. In the present study, we found that application of fenofibrate and overexpression of PPAR-alpha inhibited endothelin-1 (ET-1)-induced phosphorylation of protein kinase B (Akt) at Ser473 and glycogen synthase kinase3beta (GSK3beta) at Ser9, and prevented ET-1-induced nuclear translocation of NFATc4 in cardiomyocytes. Moreover, co-immunoprecipitation studies showed that fenofibrate strongly induced the association of nuclear factor of activated T cells (NFATc4) with PPAR-alpha. These results suggest that activation of PPAR-alpha inhibits ET-1-induced cardiac hypertrophy through regulating PI3K/Akt/GSK3beta and NFAT signaling pathways.
authors.affiliation: Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Ruifang
authors.initials: R
authors.lastname: Li
authors.forename: Wenhua
authors.initials: W
authors.lastname: Zheng
authors.forename: Rongbiao
authors.initials: R
authors.lastname: Pi
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.forename: Huijie
authors.initials: H
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Kang
authors.initials: K
authors.lastname: Le
authors.forename: Peiqing
authors.initials: P
authors.lastname: Liu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D006332:Cardiomegaly / Q000201:enzymology / Q000517:prevention & control*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000502:physiology; D011345:Fenofibrate / Q000494:pharmacology*; D005786:Gene Expression Regulation; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection
chemical_list: D019332:Endothelin-1; D050778:NFATC Transcription Factors; D009419:Nerve Tissue Proteins; C477593:Nfatc4 protein, rat; D047493:PPAR alpha; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; D011345:Fenofibrate