Exercise training improves cardiac function-related gene levels through thyroid hormone receptor signaling in aged rats
Exercise training improves cardiac function-related gene levels through thyroid hormone receptor signaling in aged rats
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DOI：
10.1152/ajpheart.00761.2003
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发表时间：
2004-05-01
影响因子：
4.8
通讯作者：
Yamaguchi, I
中科院分区：
文献类型：
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作者：
Iemitsu, M;Miyauchi, T;Yamaguchi, I
运动训练改善了衰老引起的肌球蛋白重链(MHC)和肌浆网(SR)钙-ATPase的下调，这两种酶参与了心脏收缩和松弛的调节。转录激活剂甲状腺激素受体影响MHC和SR钙-ATPase基因表达的调节。我们推测，运动训练改善老年大鼠心脏功能相关的MHC和SR钙-ATPase基因的分子机制可能与心肌组织中的受体受体信号转导有关。以久坐不动的青年大鼠(4个月龄)、久坐不动的老年大鼠(23个月龄)和训练后的老年大鼠(23个月龄，游泳训练8周)的心脏为实验对象，研究运动训练对老年大鼠心脏组织中肌质激素受体信号转导和肌浆网钙-三磷酸腺苷酶基因表达的影响。老年大鼠经训练后心功能得到改善。心脏中TR-α(1)和TR-β(1)蛋白的表达在久坐老龄大鼠显著低于久坐老龄大鼠，而在训练老龄大鼠显著高于久坐老龄大鼠。心肌组织中α-MHC和SR Ca~(2+)-ATPase基因转录调控区的TRDNA结合活性、心脏α-MHC和SR Ca~(2+)-ATPase的mRNA和蛋白表达，以及血浆3，3‘-三碘甲腺原氨酸和甲状腺激素水平的改变与心肌TRR蛋白水平的变化有关。这些结果提示，运动训练可改善衰老诱导的心肌细胞受体信号转导的MHC和SR钙-ATPase基因转录的下调，从而有助于改善训练后的老年心脏的心功能。
Exercise training improves the aging-induced downregulation of myosin heavy chain (MHC) and sarcoplasmic reticulum (SR) Ca2+-ATPase, which participate in the regulation of cardiac contraction and relaxation. Thyroid hormone receptor (TR), a transcriptional activator, affected the regulation of gene expression of MHC and SR Ca2+-ATPase. We hypothesized that myocardial TR signaling contributes to a molecular mechanism of exercise training-induced improvement of MHC and SR Ca2+-ATPase genes with cardiac function in old age. We investigated whether TR signaling and gene expression of MHC and SR Ca2+-ATPase in the aged heart are affected by exercise training, using the hearts of sedentary young rats (4 mo old), sedentary aged rats (23 mo old), and trained aged rats (23 mo old, swimming training for 8 wk). Trained aged rats showed improvement in cardiac function. Expression of TR-alpha(1) and TR-beta(1) proteins in the heart were significantly lower in sedentary aged rats than in sedentary young rats and were significantly higher in trained aged rats than in sedentary aged rats. The activity of TR DNA binding to the transcriptional regulatory region in the alpha-MHC and SR Ca2+-ATPase genes and the mRNA and protein expression of alpha-MHC and SR Ca2+-ATPase in the heart and plasma 3,3'-triiodothyronine and thyroxine levels were altered in association with changes in the myocardial TR protein levels. These findings suggest that exercise training improves the aging-induced downregulation of myocardial TR signaling-mediated transcription of MHC and SR Ca2+-ATPase genes, thereby contributing to the improvement of cardiac function in trained aged hearts.