TRs Have Common and Isoform-Specific Functions in Regulation of the Cardiac Myosin Heavy Chain Genes
Copyright policy )TRs Have Common and Isoform-Specific Functions in Regulation of the Cardiac Myosin Heavy Chain Genes
AbstractTRα1 and TRβ mediate the regulatory effects of T3 and have profound effects on the cardiovascular system. We have analyzed the expression of the cardiac myosin heavy chain (MyHC) genesα and β in mouse strains deficient for one or several TR genes to identify specific regulatory functions of TRα1 and TRβ. The results show that TRα1 deficiency, which slows the heart rate, causes chronic overexpression of MyHCβ. However, MyHCβ was still suppressible by T3 in both TRα1- and TRβ-deficient mice, indicating that either receptor can mediate repression of MyHCβ. T3-dependent induction of the positively regulated MyHCα gene was similar in both TRα1- and TRβ-deficient mice. The data identify a specific role for TRα1 in the negative regulation of MyHCβ, whereas TRα1 and TRβ appear interchangeable for hormone-dependent induction of MyHCα. This suggests that TR isoforms exhibit distinct specificities in the genes that they regulate within a given tissue type. Thus, dysregulation of MyHCβ is likely to contribute to the critical role of TRα1 in cardiac function.
- Pennsylvania State University United States
- Icahn School of Medicine at Mount Sinai United States
- Karolinska Institute Sweden
Male, Mice, Knockout, Mice, Inbred BALB C, Receptors, Thyroid Hormone, Myosin Heavy Chains, Receptors, Cytoplasmic and Nuclear, Blotting, Northern, DNA-Binding Proteins, Mice, Inbred C57BL, Mice, Gene Expression Regulation, Animals, Protein Isoforms, Triiodothyronine, Electrophoresis, Polyacrylamide Gel, Female, Cardiac Myosins, Crosses, Genetic
Male, Mice, Knockout, Mice, Inbred BALB C, Receptors, Thyroid Hormone, Myosin Heavy Chains, Receptors, Cytoplasmic and Nuclear, Blotting, Northern, DNA-Binding Proteins, Mice, Inbred C57BL, Mice, Gene Expression Regulation, Animals, Protein Isoforms, Triiodothyronine, Electrophoresis, Polyacrylamide Gel, Female, Cardiac Myosins, Crosses, Genetic
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