Iemitsu Motoyuki, Miyauchi Takashi, Maeda Seiji, Tanabe Takumi, Takanashi Masakatsu, Matsuda Mitsuo, Yamaguchi Iwao
Cardiovascular Division, Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Am J Physiol Heart Circ Physiol. 2004 May;286(5):H1696-705. doi: 10.1152/ajpheart.00761.2003. Epub 2004 Jan 2.
Exercise training improves the aging-induced downregulation of myosin heavy chain (MHC) and sarcoplasmic reticulum (SR) Ca(2+)-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 Ca(2+)-ATPase. We hypothesized that myocardial TR signaling contributes to a molecular mechanism of exercise training-induced improvement of MHC and SR Ca(2+)-ATPase genes with cardiac function in old age. We investigated whether TR signaling and gene expression of MHC and SR Ca(2+)-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-alpha1 and TR-beta1 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 Ca(2+)-ATPase genes and the mRNA and protein expression of alpha-MHC and SR Ca(2+)-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 Ca(2+)-ATPase genes, thereby contributing to the improvement of cardiac function in trained aged hearts.
运动训练可改善衰老引起的肌球蛋白重链（MHC）和肌浆网（SR）Ca（2+）-ATP酶的下调，它们参与心脏收缩和舒张的调节。甲状腺激素受体（TR）作为一种转录激活因子，影响MHC和SR Ca（2+）-ATP酶基因表达的调节。我们推测，心肌TR信号传导有助于运动训练诱导老年心脏MHC和SR Ca（2+）-ATP酶基因及心脏功能改善的分子机制。我们使用久坐不动的年轻大鼠（4月龄）、久坐不动的老年大鼠（23月龄）和训练后的老年大鼠（23月龄，进行8周游泳训练）的心脏，研究运动训练是否会影响老年心脏中TR信号传导以及MHC和SR Ca（2+）-ATP酶的基因表达。训练后的老年大鼠心脏功能有所改善。久坐不动的老年大鼠心脏中TR-α1和TR-β1蛋白的表达明显低于久坐不动的年轻大鼠，而训练后的老年大鼠心脏中TR-α1和TR-β1蛋白的表达明显高于久坐不动的老年大鼠。与心肌TR蛋白水平的变化相关，α-MHC和SR Ca（2+）-ATP酶基因转录调节区域的TR DNA结合活性、心脏中α-MHC和SR Ca（2+）-ATP酶的mRNA和蛋白表达以及血浆3,3'-三碘甲状腺原氨酸和甲状腺素水平均发生了改变。这些发现表明，运动训练可改善衰老引起的心肌TR信号传导介导的MHC和SR Ca（2+）-ATP酶基因转录下调，从而有助于改善训练后老年心脏的心脏功能。
