Effects of PPARαactivation on AngⅡ-induced cardiomyocyte hypertro-phy and interaction of NFATc4 with p65-NFκB
10.3969/j.issn.1000-4718.2014.06.010
- VernacularTitle:激活 PPARα表达对 AngⅡ诱导的心肌细胞肥大及NFATc4与 p65-NFκB 相互作用的影响
- Author:
Jian ZOU
;
Houfeng ZHOU
;
Zhiwei XIAN
;
Peiqing LIU
- Publication Type:Journal Article
- Keywords:
Angiotensin Ⅱ;
Cardiomyocyte hypertrophy;
PPARα;
NFATc4;
p65-NFκB
- From:
Chinese Journal of Pathophysiology
2014;(6):1017-1022
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To investigate the effects of fenofibrate on angiotensin Ⅱ ( AngⅡ)-induced cardiomyocyte hypertrophy .METHODS:Primary neonatal cardiomyocytes were pretreated with fenofibrate (10μmol/L) for 1 h followed by stimulation with AngⅡ(100 nmol/L).The mRNA levels of ANF, BNP andβ-MHC were measured by real-time PCR. Western blotting was employed to determine the nuclear translocations of NFATc 4 and p65-NFκB.Co-immunoprecipitation was used to investigate the interaction of NFATc 4 with p65-NFκB in the nucleus of cardiomyocytes .In addition, the DNA binding activity of NFATc4 on the BNP promoter was determined by EMSA .RESULTS:Fenofibrate significantly inhibited AngⅡ-induced cardiomyocyte hypertrophy .Fenofibrate treatment inhibited the nuclear translocations of NFATc 4 and p65-NFκB, as well as the interactions of NFATc 4 with p65-NFκB in the nucleus of cardiomyocytes induced by AngⅡ.Fenofi-brate inhibited the binding activity of NFATc 4 with the BNP promoter , which was strengthened by AngⅡ.CONCLU-SION:Fenofibrate enhances the interaction of NFATc 4 with PPARα, decreases the interaction of NFATc 4 with p65-NFκB in the nucleus of cardiomyocytes , and inhibits the DNA binding activity of NFATc 4 induced by AngⅡ, which may be the important mechanisms of fenofibrate on inhibiting cardiac hypertrophy .
