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Activation of peroxisome proliferator‐activated receptor‐α prevents glycogen synthase 3β phosphorylation and inhibits cardiac hypertrophy
Author(s) -
Li Ruifang,
Zheng Wenhua,
Pi Rongbiao,
Gao Jie,
Zhang Huijie,
Wang Ping,
Le Kang,
Liu Peiqing
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.06.017
Subject(s) - nfat , gsk 3 , phosphorylation , protein kinase b , peroxisome proliferator activated receptor , endocrinology , medicine , glycogen synthase , fenofibrate , chemistry , peroxisome proliferator activated receptor alpha , gsk3b , peroxisome , signal transduction , receptor , calcineurin , microbiology and biotechnology , biology , nuclear receptor , biochemistry , transcription factor , gene , transplantation
Activation of peroxisome proliferator‐activated receptor‐α (PPAR‐α) has been recently reported to inhibit vascular inflammatory response and prevent cardiac hypertrophy. However, it is unclear how the activation of PPAR‐α regulates hypertrophic response. In the present study, we found that application of fenofibrate and overexpression of PPAR‐α inhibited endothelin‐1 (ET‐1)‐induced phosphorylation of protein kinase B (Akt) at Ser473 and glycogen synthase kinase3β (GSK3β) 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‐α. These results suggest that activation of PPAR‐α inhibits ET‐1‐induced cardiac hypertrophy through regulating PI3K/Akt/GSK3β and NFAT signaling pathways.