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KCI등재 학술저널

Thyroid Hormone-Induced Alterations of Ca<SUP>2&#8290;</SUP>-ATPase and Phospholamban Protein Expression in Cardiac Sarcoplasmic Reticulum

Thyroid Hormone-Induced Alterations of Ca<SUP>2&#8290;</SUP>-ATPase and Phospholamban Protein Expression in Cardiac Sarcoplasmic Reticulum

<P> Alterations of cardiovascular function associated with various thyroid states have been studied. In hyperthyroidism left ventricular contractility and relaxation velocity were increased, whereas these parameters were decreased in hypothyroidism. The mechanisms for these changes have been suggested to include alterations in the expression and/or activity levels of various proteins; α-myosin heavy chain, β- myosin heavy chain, β-receptors, the guanine nucleotide-binding regulatory protein, and the sarcolemmal Ca<SUP>2&#8290;</SUP>-ATPase. All these cellular alterations may be associated with changes in the intracellular Ca<SUP>2&#8290;</SUP> concentration. The most important regulator of intracellular Ca<SUP>2&#8290;</SUP> concentration is the sarcoplasmic reticulum (SR), which serves as a Ca<SUP>2&#8290;</SUP> sink during relaxation and as a Ca<SUP>2&#8290;</SUP> source during contraction. The Ca<SUP>2&#8290;</SUP>-ATPase and phospholamban are the most important proteins in the SR membrane for muscle relaxation. The dephosphorylated phospholamban inhibits the SR Ca<SUP>2&#8290;</SUP>-ATPase through a direct interaction, and phosphorylation of phospholamban relieves the inhibition. In the present study, quantitative changes of Ca<SUP>2&#8290;</SUP>-ATPase and phospholamban expression and the functional consequences of these changes in various thyroid states were investigated. The effects of thyroid hormones on (1) SR Ca<SUP>2&#8290;</SUP> uptake, (2) phosphorylation levels of phospholamban, (3) SR Ca<SUP>2&#8290;</SUP>-ATPase and phospholamban protein levels, (4) phospholamban mRNA levels were examined. Our findings indicate that hyperthyroidism is associated with increases in Ca<SUP>2&#8290;</SUP>-ATPase and decreases in phospholamban levels whereas opposite changes in these proteins occur in hypothyroidism.

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