Roles of transcriptional corepressor RIP140 and coactivator PGC-1α in energy state of chronically infarcted rat hearts and mitochondrial function of cardiomyocytes
Transcriptional coactivator PPARγ coactivator-1α (PGC-1α) and corepressor receptor-interacting protein 140 (RIP140) are opposing-functional regulators in maintaining energy balance of most metabolic tissues and cells.However,the relative contributions of both factors to energy metabolism in cardiomyocytes remain largely unknown.Herein,we reported that the relative protein levels of RIP140/PGC-1α were up-regulated in the failing hearts after chronic myocardial infarction (MI),and correlated negatively with the energy state index phosphocreatine (PCr)/ATP ratios.Real-time PCR analysis revealed that mRNA expressions of estrogen related receptor αt (ERRα),peroxisome proliferate activated receptor a and β (PPARα,PPARβ),nuclear respiratory factor 1(NRF1) and their target genes were repressed by RIP140 and induced by PGC-1α in a dose dependent manner in neonatal rat cardiomyocytes.We also observed that overexpression of RIP140 through adenovirus delivery can abrogate the PGC-1α-mediated induction of mitochondrial membrane potential elevation and mitochondrial biogenesis,and activateboth autophagy and apoptosis pathways.We conclude that RIP140 and PGC-1α exert antagonistic role in regulating cardiac energy state and mitochondrial biogenesis.
PGC-1α RIP140 Heart failure Adenovirus Metabolism Mitochondrial biogenesis
Yanfang Chen Yuhua Wang Jianwen Chen Xi Chen Weiwei Cao Shaorui Chen Suowen Xu Heqing Huang Peiqing Liu
Department of Pharmacology and Toxicology,School of Pharmaceutical Sciences,Sun Yat-sen University,G Institute of Pharmacy and Pharmacology,Nanhua University,Hengyang,Hunan,China
国内会议
广州
英文
83-97
2013-01-12（万方平台首次上网日期，不代表论文的发表时间）