title: Roles of transcriptional corepressor RIP140 and coactivator PGC-1α in energy state of chronically infarcted rat hearts and mitochondrial function of cardiomyocytes.
abstract: 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 α (ERRα), peroxisome proliferate activated receptor α 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 activate both autophagy and apoptosis pathways. We conclude that RIP140 and PGC-1α exert antagonistic role in regulating cardiac energy state and mitochondrial biogenesis.
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Chen
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Wang
authors.forename: Jianwen
authors.initials: J
authors.lastname: Chen
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Weiwei
authors.initials: W
authors.lastname: Cao
authors.forename: Shaorui
authors.initials: S
authors.lastname: Chen
authors.forename: Suowen
authors.initials: S
authors.lastname: Xu
authors.forename: Heqing
authors.initials: H
authors.lastname: Huang
authors.forename: Peiqing
authors.initials: P
authors.lastname: Liu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D018929:Cell Culture Techniques; D004734:Energy Metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005786:Gene Expression Regulation; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D008297:Male; D053858:Metabolic Networks and Pathways; D008929:Mitochondria, Heart / Q000378:metabolism* / Q000502:physiology; D063269:Mitochondrial Turnover; D009203:Myocardial Infarction / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000078723:Nuclear Receptor Interacting Protein 1; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010725:Phosphocreatine / Q000378:metabolism; D061251:Primary Cell Culture; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D005230:Fatty Acids, Nonesterified; D009687:Nuclear Proteins; D000078723:Nuclear Receptor Interacting Protein 1; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D010725:Phosphocreatine; D000255:Adenosine Triphosphate