The effect of relgulation of PPAR-α on cardiac hypertrophy and the relationship between the effect of PPAR-α with PI3K/Akt/mTOR pathway.
- Author:
Yang WU
;
Bao-xia WANG
;
Yuan-yuan GUO
;
Yu-qin WANG
- Publication Type:Journal Article
- MeSH: Atrial Natriuretic Factor; metabolism; Cardiomegaly; metabolism; Cells, Cultured; Fenofibrate; pharmacology; Humans; Isoproterenol; adverse effects; Myocytes, Cardiac; drug effects; metabolism; Myosin Heavy Chains; metabolism; PPAR alpha; metabolism; Phosphatidylinositol 3-Kinases; metabolism; Proto-Oncogene Proteins c-akt; metabolism; RNA, Messenger; Ribosomal Protein S6 Kinases, 70-kDa; metabolism; Signal Transduction; TOR Serine-Threonine Kinases; metabolism
- From: Chinese Journal of Applied Physiology 2015;31(3):284-288
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effect of peroxisiome proliferator activated receptor-α (PPAR-α) on the regulation of cardiomyocyte hypertrophy and the relationship between the effect of PPAR-α with PI3K/Akt//mTOR signal pathway.
METHODSCardiomyocyte hypertrophy was induced by isoproterenol (ISO). The cell surface area was measured by image analysis system (Leica). The expressions of atrial natriuretic peptide (ANP), β-myosin heavy chain (β-MHC) and PPAR-α mRNA were detected by qRT-PCR. The protein expressions of Akt, mTOR and P70S6K were detected by Western blot. The expression of PPAR-α was suppressed by RNAi.
RESULTS(1) The expression of PPAR-α was significantly reduced in cardiomyocyte hypertrophy. PPAR-α activator Fenofibrate (Feno) increased the expression of PPAR-α and suppressed cardiomyocyte hypertrophy. The inhibitory effect of Feno on cardiomyocyte hypertrophy was reversed by PPAR-α RNAi. (2) Feno significantly inhibited the increase of the protein expressions of p-Akt, p-mTOR and p-p70S6K in ISO induced cardiomyocyte hypertrophy, which could be blocked by PPAR-α RNAi. (3) PI3K antagonist LY294002 (LY) or mTOR antagonist rapamycin (RAPA) markedly-inhibited cardiomyocyte hypertrophy. The inhibitory effects of LY or RAPA on cardiomyocyte hypertrophy were reversed by PPAR-α RNAi.
CONCLUSIONPPAR-α can negatively regulate cardiomyocyte hypertrophy. The effect might be associated with PPAR-α inhiting PI3K/ Akt/mTOR signal pathway.