Cross-talk between transcriptional regulation by thyroid hormone and myogenin: new aspects of the Ca2+-dependent expression of the fast-type sarcoplasmic reticulum Ca2+-ATPase.
Cross-talk between transcriptional regulation by thyroid hormone and myogenin: new aspects of the Ca2+-dependent expression of the fast-type sarcoplasmic reticulum Ca2+-ATPase.
复制标题
甲状腺激素和肌生成素转录调节之间的串扰：快速型肌浆网 Ca2+-ATP 酶的 Ca2+ 依赖性表达的新方面。
DOI：
--
复制
发表时间：
1998
影响因子：
4.1
通讯作者：
C. van Hardeveld
中科院分区：
文献类型：
--
作者：
M. Thelen;W. Simonides;A. Muller;C. van Hardeveld
我们以前已经证明了骨骼肌表型的主要决定因素之间的相互作用，通过显示连续收缩活动抑制甲状腺激素（3，3 '，5-三碘甲状腺原氨酸; T3）依赖的转录活性的快速型肌质/内质网Ca 2 +-ATP酶（SERCA 1），快速表型的特征。细胞内游离Ca ~（2+）浓度（[Ca ~（2+）]i）和成肌决定因子MyoD和肌细胞生成素（myogenin）都被认为是收缩活动对骨骼肌表型影响的介质。使用L 6细胞，我们已经表明，稳态[Ca 2 +]i高于120 nM的静息水平的增加确实可以模拟收缩活性对T3依赖性SERCA 1表达的影响。我们现在表明，增加[Ca 2 +]i对T3依赖的SERCA 1在L 6细胞中的表达的抑制作用是在翻译前水平发挥作用，并伴随着肌细胞生成素mRNA表达的增加。在这些细胞中肌细胞生成素的过度表达表明，单独肌细胞生成素的表达增加强烈降低了SERCA 1启动子活性的T3依赖性刺激。这些结果表明，骨骼肌表型的调节途径，其中[Ca 2 +]i介导的收缩活性的影响，通过调节肌细胞生成素的表达，这反过来又干扰转录调节T3。
We have previously demonstrated an interaction between the major determinants of skeletal muscle phenotype by showing that continuous contractile activity represses the thyroid hormone (3,3', 5-tri-iodothyronine; T3)-dependent transcriptional activity of fast-type sarcoplasmic/endoplasmic-reticulum Ca2+-ATPase (SERCA1), a characteristic of the fast phenotype. Both the free cytosolic Ca2+ concentration ([Ca2+]i) and the myogenic determination factors MyoD and myogenin have been implicated as mediators of the effect of contractile activity on skeletal muscle phenotype. Using L6 cells we have shown that an increase in the steady-state [Ca2+]i above the resting level of 120 nM indeed can mimic the effect of contractile activity on T3-dependent SERCA1 expression. We now show that the repressing effect of increased [Ca2+]i on T3-dependent SERCA1 expression in L6 cells is exerted at a pre-translational level and is accompanied by increased myogenin mRNA expression. Myogenin overexpression in these cells revealed that increased expression of myogenin alone strongly decreases the T3-dependent stimulation of SERCA1 promoter activity. These results suggest a pathway for the regulation of skeletal muscle phenotype in which [Ca2+]i mediates the effect of contractile activity by regulating the expression of myogenin, which in turn interferes with transcriptional regulation by T3.