EFFECT OF THYROID-HORMONE ON THE EXPRESSION OF MESSENGER-RNA ENCODING SARCOPLASMIC-RETICULUM PROTEINS
EFFECT OF THYROID-HORMONE ON THE EXPRESSION OF MESSENGER-RNA ENCODING SARCOPLASMIC-RETICULUM PROTEINS
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DOI：
10.1161/01.res.69.2.266
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发表时间：
1991-08-01
影响因子：
20.1
通讯作者：
PERIASAMY, M
中科院分区：
文献类型：
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作者：
ARAI, M;OTSU, K;PERIASAMY, M
本研究的目的是确定在甲状腺激素诱导的心肌肥大过程中，与钙释放、摄取和储存功能相关的各种肌浆网成分编码基因的表达。用L甲状腺素(T4)200mg/kg/d连续4d(T4~4d组)和8d(T4~8d组)诱导两组兔甲亢模型。另一组在饮水中加入0.8 mg/ml丙基硫氧嘧啶，连续4周诱发甲状腺功能减退。通过RNA狭缝印迹和Northern印迹分析，确定不同肌浆网蛋白编码基因的相对表达水平。在甲亢组，心肌Ryanodine受体和肌浆网钙/慢收缩钙-ATPase 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)，而在甲低组分别下降到71%(P<0.05)和75%。在这些心脏中，甲亢(T4-8天组，72%)和甲减(77%)的磷蛋白基因表达水平均降低。另一方面，在甲状腺功能亢进和甲状腺功能减退的脑室中，Calequestrin的mRNA水平没有变化。与Ca~(2+)-ATPase mRNA水平的变化相一致，甲亢大鼠脑室组织中的Ca~(2+)-ATPase蛋白表达水平升高至199%(T4~8日龄组)，而甲减大鼠脑室组织中的Ca~(2+)-ATPase蛋白表达水平下降至对照组的86%。在甲亢和甲减兔骨骼肌组织中，Ryanodine受体、Ca~(2+)-ATPase、磷蛋白和钙调素的表达水平也发生了类似的变化。这些结果表明，心肌和骨骼肌中负责钙释放和钙吸收的肌浆网蛋白的mRNA水平是受甲状腺激素水平变化的协调调节的。这些mRNA水平的变化应该会导致蛋白质水平的变化，从而改变甲亢和甲减慢性阶段的钙释放和摄取。
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-mu-g/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 Ca2+-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 hyperthyrodism (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 Ca2+-ATPase mRNA levels, the Ca2+-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, Ca2+-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.