Thyroid hormone stimulates Na, K-ATPase gene expression in the hemodynamically unloaded heterotopically transplanted rat heart.
Thyroid hormone stimulates Na, K-ATPase gene expression in the hemodynamically unloaded heterotopically transplanted rat heart.
复制标题
甲状腺激素刺激血流动力学卸载的异位移植大鼠心脏中 Na、K-ATP 酶基因的表达。
DOI：
10.1089/thy.2000.10.753
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Ismail-Beigi,F
中科院分区：
文献类型：
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作者：
Shao,Y;Ojamaa,K;Klein,I;Ismail-Beigi,F
在异位移植的大鼠心脏中研究甲状腺激素对心肌Na，K-ATP酶基因表达的调节，以区分甲状腺激素对心脏的直接影响和继发于血流动力学负荷增加的影响。在这个模型中，移植的心脏在组织学上是正常的，并且自发地跳动，但是血流动力学上是卸载的。移植后3d，心室Na，K-ATP酶α2-和β1-mRNAs及α1-和α2-蛋白的相对含量增加2 ~ 3倍，但这些变化是短暂的。接下来，我们确定了在心脏中Na，K-ATP酶表达的各种参数中观察到的三碘甲状腺原氨酸（T3）诱导的最大变化：用T3处理非移植的甲状腺功能正常大鼠以达到甲状腺功能亢进的稳态，导致心脏重量、RNA和RNA/蛋白比、Na，K-ATP酶活性、Na，K-ATP酶α2-蛋白和酶活性显著增加，α2-和β1-mRNA含量增加约3倍。然后检查甲状腺素（T4）对异位移植心脏和原位心脏的作用。T4处理（宿主的）导致移植心脏中Na，K-ATP酶α1-、α2-和α1-mRNA的显著增加（分别为1.6 ± 0.1、2.4 ± 0.2和1.7 ± 0.1倍），与稀释处理的甲状腺功能正常宿主的移植心脏相比，（所有变化p>0.05）。此外，T4诱导的移植心脏增量与T4处理的宿主大鼠相应原位心脏中观察到的增量相似。我们的结论是，增加Na，K-ATP酶的表达，甲状腺激素在很大程度上发生独立的增加心脏工作引起的激素，并反映了直接作用的激素对Na，K-ATP酶基因的表达。
Regulation of myocardial Na, K-ATPase gene expression by thyroid hormone was investigated in the heterotopically transplanted rat heart to distinguish the direct effects of the hormone on the heart from effects secondary to increased hemodynamic workload. In this model, the transplanted heart is histologically normal and spontaneously beating, but hemodynamically unloaded. Three days after transplantation, relative contents of ventricular Na, K-ATPase α2- and β1-mRNAs and α1- and α2-proteins were increased twofold to threefold in the transplanted heart, but these changes were transient. We next determined the maximal triiodothyronine (T3)-induced changes that are observed in various parameters of Na, K-ATPase expression in the heart: treatment of nontransplanted euthyroid rats with T3to reach hyperthyroid steady state resulted in significant increases in heart weight, RNA and RNA/protein ratio, Na, K-ATPase activity, Na, K-ATPase α2-protein and enzyme activity, and approximately threefold increase in both α2- and β1-mRNA content. The effect of treatment with thyroxine (T4) on the heterotopically transplanted and thein situheart was then examined. T4treatment (of the host) resulted in a significant increase in Na, K-ATPase α1-, α2-, and α1-mRNAs in transplanted hearts (1.6 ± 0.1-, 2.4 ± 0.2-, and 1.7 ± 0.1-fold, respectively), that was associated with a 2.2 ± 0.2-fold increase in α2protein as compared to transplanted hearts in diluent-treated euthyroid hosts (p>0.05 for all changes). In addition, T4-induced increments in transplanted hearts were similar to those observed in the correspondingin situhearts of host rats treated with T4. We conclude that the increase in Na, K-ATPase expression by thyroid hormone largely occurs independently of increased cardiac work elicited by the hormone and reflects a direct action of the hormone on Na, K-ATPase gene expression.