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The protective role of peroxisome proliferator‐activated receptor γ coactivator‐1α in hyperthyroid cardiac hypertrophy
Author(s) -
Xu Wei,
Hou Dongxia,
Jiang Xiangrui,
Lu Zhiyuan,
Guo Ting,
Liu Yuan,
Wang Dongjin,
Zen Ke,
Yu Bo,
Zhang ChenYu
Publication year - 2012
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24015
Subject(s) - coactivator , peroxisome proliferator activated receptor , medicine , mapk/erk pathway , endocrinology , triiodothyronine , p38 mitogen activated protein kinases , muscle hypertrophy , small interfering rna , kinase , receptor , biology , nuclear receptor , stimulation , microbiology and biotechnology , chemistry , thyroid , rna , transcription factor , gene , biochemistry
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. J. Cell. Physiol. 227: 3243–3253, 2012. © 2012 Wiley Periodicals, Inc.