Regulation of SERCA 2 expression by thyroid hormone in cultured chick embryo cardiomyocytes.
We investigated the role of thyroid hormone in the physiological perinatal increase in cardiac sarcoplasmic reticulum (SR) Ca(2+)-adenosinetriphosphatase (ATPase) expression. We isolated and cultured the cardiomyocytes in 10(-8) M triiodothyronine (T3) for 48 h and then measured SR Ca(2+)-ATPase mRNA and immunodetectable protein contents as well as SR-dependent 45Ca2+ uptake rate. We also examined the effect of T3 on expression of the same gene in monkey kidney CV-1 cells, which do not express thyroid hormone receptors. T3 increased cardiomyocyte SR Ca2+ pump mRNA content by 289 +/- 35%, and immunodetectable SR Ca2+ pump protein content by 255 +/- 44%, and SR-specific 45Ca2+ uptake rate by 189 +/- 22% (P < 0.01 for each). In contrast, T3 had no significant effect on the total cellular RNA or protein contents in the cardiomyocyte, and there was no effect of T3 on Ca(2+)-ATPase mRNA content in the thyroid hormone receptor-negative CV-1 cells. These data demonstrate that T3 increases expression of the cardiac SR Ca2+ pump, that the effect can be localized to the cardiomyocyte, and that the effect is dependent on thyroid hormone receptors. These data are consistent with pretranslational and possibly transcriptional level effect of thyroid hormone on the cardiac SR Ca2+ pump gene (SERCA 2). The gestation-associated increase in thyroid hormone may be at least partially responsible for the previously demonstrated perinatal increase in cardiac SR Ca2+ pump expression.
Fisher
D J
DJ
Lillie Frank Abercrombie Section of Pediatric Cardiology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
Phillips
S
S
McQuinn
T
T
D000818:Animals; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000235:genetics*; D002478:Cells, Cultured; D002642:Chick Embryo; D015870:Gene Expression / Q000187:drug effects*; D006321:Heart / Q000196:embryology / Q000502:physiology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D014284:Triiodothyronine / Q000494:pharmacology*
D012333:RNA, Messenger; D014284:Triiodothyronine; D000252:Calcium-Transporting ATPases; D002118:Calcium