Arai M, Otsu K, MacLennan D H, Alpert N R, Periasamy M
Department of Physiology and Biophysics, University of Vermont College of Medicine, Burlington 05405.
Circ Res. 1991 Aug;69(2):266-76. doi: 10.1161/01.res.69.2.266.
The purpose of this study was to determine the expression of genes encoding various sarcoplasmic reticulum components that are functionally coupled with calcium release, uptake, and storage function during cardiac hypertrophy induced by thyroid hormone. Hyperthyroidism was induced in two groups of rabbits by the injection of 200 micrograms/kg L-thyroxine (T4) daily for 4 days (T4-4-day group) and 8 days (T4-8-day group). Hypothyroidism was induced in another group of rabbits by adding 0.8 mg/ml propylthiouracil to the drinking water for 4 weeks. The relative expression level of mRNA encoding different sarcoplasmic reticulum proteins was determined by RNA slot blot and Northern blot analysis. In hyperthyroid hearts, the steady-state level of cardiac ryanodine receptor mRNA and sarcoplasmic reticulum cardiac/slow-twitch Ca(2+)-ATPase mRNA were both increased to 147% (T4-4-day group) and 186% (T4-8-day group) of control, respectively, but decreased to 71% and 75%, respectively, in hypothyroid ventricles. The mRNA level for phospholamban was decreased in both hyperthyroidism (T4-8-day group, 72%) and hypothyroidism (77%) in these hearts. On the other hand, calsequestrin mRNA levels did not change in hyperthyroid and hypothyroid ventricles. In accord with the changes in Ca(2+)-ATPase mRNA levels, the Ca(2+)-ATPase protein was increased to 199% (T4-8-day group) in hyperthyroid ventricles and decreased to 86% of control in hypothyroid ventricles. The expression levels of ryanodine receptor, Ca(2+)-ATPase, phospholamban, and calsequestrin mRNAs were similarly altered in skeletal muscle tissues from hyperthyroid and hypothyroid rabbits. These results indicate that the mRNA levels of sarcoplasmic reticulum proteins responsible for calcium release and calcium uptake are coordinately regulated in response to changes in thyroid hormone level in both heart and skeletal muscle. These changes in mRNA level should lead to changes in protein levels and thus to altered calcium release and uptake in the chronic stages of hyperthyroidism and hypothyroidism.
本研究的目的是确定在甲状腺激素诱导的心脏肥大过程中，编码各种肌浆网成分的基因的表达情况，这些成分在功能上与钙的释放、摄取和储存功能相关。通过每天注射200微克/千克L-甲状腺素（T4），连续4天（T4-4天组）和8天（T4-8天组），诱导两组兔子发生甲状腺功能亢进。通过在饮用水中添加0.8毫克/毫升丙硫氧嘧啶4周，诱导另一组兔子发生甲状腺功能减退。通过RNA斑点印迹和Northern印迹分析，确定编码不同肌浆网蛋白的mRNA的相对表达水平。在甲状腺功能亢进的心脏中，心脏雷诺丁受体mRNA和肌浆网心脏/慢肌钙（2+）-ATP酶mRNA的稳态水平分别增加到对照组的147%（T4-4天组）和186%（T4-8天组），但在甲状腺功能减退的心室中分别降至71%和75%。在这些心脏中，受磷蛋白的mRNA水平在甲状腺功能亢进（T4-8天组，72%）和甲状腺功能减退（77%）时均降低。另一方面，在甲状腺功能亢进和减退的心室中，肌集钙蛋白mRNA水平没有变化。与钙（2+）-ATP酶mRNA水平的变化一致，钙（2+）-ATP酶蛋白在甲状腺功能亢进的心室中增加到199%（T4-8天组），在甲状腺功能减退的心室中降至对照组的86%。甲状腺功能亢进和减退兔子的骨骼肌组织中，雷诺丁受体、钙（2+）-ATP酶、受磷蛋白和肌集钙蛋白mRNA的表达水平也有类似变化。这些结果表明，在心脏和骨骼肌中，负责钙释放和摄取的肌浆网蛋白的mRNA水平会随着甲状腺激素水平的变化而协同调节。mRNA水平的这些变化应会导致蛋白质水平的变化，从而在甲状腺功能亢进和减退的慢性阶段改变钙的释放和摄取。
