Thyroid hormone regulates Ca2+-ATPase mRNA levels of sarcoplasmic reticulum during neonatal development of fast skeletal muscle

We have produced seven lines of transgenic mice carrying the quail gene encoding the fast skeletal muscle-specific isoform of troponin I (TnIf). The quail DNA included the entire TnIf gene, 530 base pairs of 5'-flanking DNA, and 1.5 kilobase pairs of 3'-flanking DNA. In all seven transgenic lines, normally initiated and processed quail TnIf mRNA was expressed in skeletal muscle, where it accumulated to levels comparable to that in quail muscle. Moreover, in the three lines tested, quail TnIf mRNA levels were manyfold higher in a fast skeletal muscle (gastrocnemius) than in a slow skeletal muscle (soleus). We conclude that the cellular mechanisms directing muscle fiber type-specific TnIf gene expression are mediated by cis-regulatory elements present on the introduced quail DNA fragment and that they control TnIf expression by affecting the accumulation of TnIf mRNA. These elements have been functionally conserved since the evolutionary divergence of birds and mammals, despite the major physiological and morphological differences existing between avian (tonic) and mammalian (twitch) slow muscles. In lines of transgenic mice carrying multiple tandemly repeated copies of the transgene, an aberrant quail TnIf transcript (differing from normal TnIf mRNA upstream of exon 2) also accumulated in certain tissues, particularly lung, brain, spleen, and heart tissues. However, this aberrant transcript was not detected in a transgenic line which carries only a single copy of the quail gene.

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Rabbit skeletal muscle sarcoplasmic reticulum Ca2+-ATPase activity: stimulation in vitro by thyroid hormone analogues and bipyridines

Biochimica et Biophysica Acta (BBA) - Biomembranes ◽

10.1016/0005-2736(93)90404-n ◽

1993 ◽

Vol 1153 (2) ◽

pp. 184-190 ◽

Cited By ~ 23

Author(s):

Pamela R. Warnick ◽

Paul J. Davis ◽

Faith B. Davis ◽

Vivian Cody ◽

Galindo Jose ◽

...

Keyword(s):

Skeletal Muscle ◽

Thyroid Hormone ◽

Sarcoplasmic Reticulum ◽

Atpase Activity ◽

Rabbit Skeletal Muscle

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Differential regulation of the expression of fast-type sarcoplasmic-reticulum Ca2+-ATPase by thyroid hormone and insulin-like growth factor-I in the L6 muscle cell line

Biochemical Journal ◽

10.1042/bj3030467 ◽

1994 ◽

Vol 303 (2) ◽

pp. 467-474 ◽

Cited By ~ 9

Author(s):

M H M Thelen ◽

A Muller ◽

M J Zuidwijk ◽

G C van der Linden ◽

W S Simonides ◽

...

Keyword(s):

Transcriptional Regulation ◽

Growth Factor ◽

Thyroid Hormone ◽

Sarcoplasmic Reticulum ◽

Mrna Stability ◽

Half Life ◽

Mrna Levels ◽

Factor I ◽

Igf I ◽

Mrna Half Life

The aim of this study was to investigate the mechanism(s) underlying the thyroid-hormone (L-tri-iodothyronine, T3)-induced elevation of fast-type sarcoplasmic-reticulum Ca(2+)-ATPase (SERCA1) levels in L6 myotubes and the potentiating effect of insulin-like growth factor-I (IGF-I) [Muller, van Hardeveld, Simonides and van Rijn (1991) Biochem. J. 275, 35-40]. T3 increased the SERCA1 protein level (per microgram of DNA) by 160%. The concomitant increase in the SERCA1 mRNA level was somewhat higher (240%). IGF-I also increased SERCA1 protein (110%) and mRNA levels (50%), whereas IGF-I + T3 increased SERCA1 protein and mRNA levels by 410% and 380% respectively. These SERCA1 mRNA analyses show that the more-than-additive action of T3 and IGF-I on SERCA1 expression is, at least in part, pre-translational in nature. Further studies showed that the half-life of SERCA1 protein in L6 cells (17.5 h) was not altered by T3. In contrast, IGF-I prolonged the half-life of SERCA1 protein 1.5-1.9-fold, which may contribute to the disproportional increase in SERCA1 protein content compared with mRNA by IGF-I. Measurements of SERCA1 mRNA half-life (as determined by actinomycin D chase) showed no difference from the control values (15.5 h) in the presence of T3 or IGF-I alone. When T3 and IGF-I were both present, the SERCA1 mRNA half-life was prolonged 2-fold. No significant effects of T3 and IGF-I were observed on the half-life of total protein (37.4 h) and total RNA (37.0 h). The absence of an effect of T3 on SERCA1 protein and mRNA stability, when it was present alone, suggested transcriptional regulation, which was confirmed by nuclear run-on experiments, showing a 3-fold increase in transcription frequency of the SERCA1 gene by T3. We conclude that the synergistic stimulating effects of T3 and IGF-I on SERCA1 expression are the result of both transcriptional and post-transcriptional regulation. T3 acts primarily at the transcriptional level by increasing the transcription frequency of the SERCA1 gene, whereas IGF-I seems to act predominantly at post-transcriptional levels by enhancing SERCA1 protein and mRNA stability, the latter, however, only in the presence of T3.

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