摘要
目的探讨转录辅助因子受体相互作用蛋白140(receptor interacting protein 140,RIP140)与过氧化物酶体增殖物受体γ共激活因子1α(peroxisome proliferator-activated receptor gamma coactivator-1α,PGC-1α)在血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)调节心肌细胞能量代谢中的作用。方法借助腺病毒载体系统诱导RIP140和PGC-1α基因过表达;利用荧光检测系统测定乳鼠心肌细胞线粒体ATP的含量;实时荧光定量PCR和Western blot的方法检测RIP140和PGC-1α的表达情况。结果乳鼠心肌细胞给予100 nmol·L-1AngⅡ刺激36 h后,心肌细胞线粒体ATP的含量降低(P<0.01),同时伴随RIP140 mRNA与蛋白水平的升高,而PGC-1αmRNA与蛋白水平下调。AngⅡ诱导的ATP含量减少在过表达RIP140组中进一步下降,而在过表达PGC-1α组中有所减轻。结论AngⅡ诱导的ATP含量减少与RIP140表达上调和PGC-1α表达下调有关。
Aim To investigate the role of transcriptional cofactors receptor interacting protein 140( RIP140) and peroxisome proliferator-activated receptor γ coactivator-1α( PGC-1α) in the angiotensin Ⅱ( Ang Ⅱ) mediated energy metabolism regulation in cardiomyocytes. Methods RIP140 or PGC-1α was overexpressed via adenovirus vector system. ATP contents were detected by luminescence detection assay system. Real-time PCR and Western blot analysis were used to measure the expressions of RIP140 and PGC-1α genes. Results After treated with 100 nmol·L- 1Ang Ⅱ for 36 h in neonatal cardiomyocytes,the content of mitochondrial ATP was reduced notably( P <0. 01). Accordingly,the mRNA and protein levels for RIP140 were increased. However,the mRNA and protein levels of PGC-1α were downregulated markedly.What's more,the reduction of ATP induced by Ang Ⅱwas further aggravated by RIP 1 4 0 overexpression,butameliorated by overexpressing PGC-1α. Conclusion The reduction of ATP mediated by AngⅡ is associated with the upregulation of RIP140,as well as the downregulation of PGC-1α.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2015年第2期194-198,共5页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No 81402923)
广州医科大学博士启动金(No 2012C41)
广东省临床用药研究基金-施慧达心血管用药研究基金(No 2013X61)
关键词
血管紧张素Ⅱ
RIP140
PGC-1Α
ATP
能量代谢
心肌细胞
angiotensin Ⅱ
receptor interacting protein 140
peroxisome proliferator-activated receptor gamma coactivator-1α
ATP
energy metabolism
cardiomyocytes
