title: The protective role of peroxisome proliferator-activated receptor γ coactivator-1α in hyperthyroid cardiac hypertrophy.
abstract: Heart failure is a major cause of death throughout the world. Hyperthyroidism has been shown to induce cardiac hypertrophy, which is a contributing factor to heart failure. However, the mechanism underling effect of thyroid hormone is not completely clear. The present study investigates the role of peroxisome proliferator-activated receptor (PPAR) γ coactivator-1α (PGC-1α) in cardiac hypertrophy induced by Triiodothyronine (T3). We investigated PGC-1α mRNA expression in rat hearts exposed to T3 in vivo and ex vivo. Surprisingly, we found that the extended periods of T3 treatment led to an increase in PGC-1α expression compared to shorter treatment times, which resulted in a reduction of PGC-1α expression. Mechanistic studies showed that suppression of PGC-1α by small interfering RNA in cardiomyocytes amplified the cellular hypertrophic response to T3 stimulation, whereas overexpression of PGC-1α was protective. Furthermore, we presented evidence to show that T3 decreased PGC-1α expression via p38 mitogen-activated protein kinases (MAPK) pathway. Our studies also revealed that overexpression of PGC-1α in cardiomyocytes inhibited basal and T3-induced p38 MAPK phosphorylation. These data indicate for the first time that PGC-1α plays protective role in T3-induced cardiac hypertrophy and that hypertrophic growth induced by T3 involves a regulatory pathway between PGC-1α and p38 MAPK.
authors: Jiangsu Diabetes Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
authors: Wei
authors: W
authors: Xu
authors: Dongxia
authors: D
authors: Hou
authors: Xiangrui
authors: X
authors: Jiang
authors: Zhiyuan
authors: Z
authors: Lu
authors: Ting
authors: T
authors: Guo
authors: Yuan
authors: Y
authors: Liu
authors: Dongjin
authors: D
authors: Wang
authors: Ke
authors: K
authors: Zen
authors: Bo
authors: B
authors: Yu
authors: Chen-Yu
authors: CY
authors: Zhang
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000209:etiology / Q000378:metabolism*; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D006980:Hyperthyroidism / Q000139:chemically induced / Q000150:complications; D032383:Myocytes, Cardiac / Q000378:metabolism; D010101:Oxygen Consumption; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010766:Phosphorylation / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000235:genetics*; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014284:Triiodothyronine / Q000008:administration & dosage / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D014284:Triiodothyronine; D048051:p38 Mitogen-Activated Protein Kinases