How does thyroid  hormone  regulate  SR-Ca2+ ATPase  (SERCA) protein in the heart?
['Furthermore, using specific inhibitors of the TH-activated kinases, we show that the long-term effects of TH on the expression of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA), alpha- and beta-myosin heavy chain (MHC) and cell growth are reverted, implying that what is initiated as a non-genomic action of the hormone interfaces with genomic effects.', 'Hypothyroid neonates showed increased cholesterol levels and decreased expression of D1 in liver and of Serca-2 in heart, which were normalized with T3 treatment.', 'ERCA2 transcript and protein levels were reduced in FOG-2 transgenic hearts, and FOG-2 overexpression impaired T3-mediated SERCA2 expression in cultured cardiomyocytes. FOG-2 physically interacts with thyroid hormone receptor-alpha1 and abrogated even high levels of T3-mediated SERCA2 promoter activity.', 'A marked elevation of the expression of beta-MHC and a reduced ratio of SERCA/Phospholamban were found in viable myocardium of AMI hearts, which was prevented by TH', 'After TH treatment, AMI-THYR hearts expressed 71% alpha-MHC and 29% beta-MHC, P<0.05 versus SHAM and AMI and the ratio of SERCA/PLB was increased by 2.0-fold, P<0.05 versus SHAM and AMI.', 'Because the binding of T(3) occupied receptors to the thyroid response elements in the SERCA promotor can increase gene expression', 'These results demonstrate that increasing TR expression in the hypertrophied heart is associated with an improvement in contractile function and increased SERCA expression.', 'Increased cardiac D2 activity led to elevated cardiac T3 levels and to enhanced myocardial contractility, accompanied by increased Ca(2+) transients and sarcoplasmic reticulum (SR) Ca(2+) uptake. These phenotypic changes were associated with up-regulation of sarco(endo)plasmic reticulum calcium ATPase (SERCA) 2a expression', 'Our results establish that elevated D2 activity in the heart increases T3 levels and enhances cardiac contractile function while preventing deterioration of cardiac function', 'Hypothyroid heart displays a phenotype of cardioprotection against ischemia and this study investigated whether administration of dronedarone, an amiodarone-like compound that has been shown to preferentially antagonize thyroid hormone binding to thyroid hormone receptor alpha1 (TRalpha1), results in a similar effect. Dronedarone was given in Wistar rats (90 mg/kg, once daily (od) for 2 weeks) (DRON), while untreated animals served as controls (CONT). Hypothyroidism (HYPO) was induced by propylthiouracil administration.', 'while beta-myosin heavy chain (beta-MHC) and sarcoplasmic reticulum Ca2+ adenosine triphosphatase (ATPase) expression (SERCA) was similar to CONT. In HYPO, alpha-MHC and SERCA were decreased while beta-MHC was increased.', 'the postnatal switch from beta- to alpha-myosin heavy chain (beta- and alpha-MHC, respectively) gene expression and the increase of SERCA-2a mRNA expression did not occur in the ventricular myocardium of either the transgenic (thyroid destroyed) or nontransgenic (intact thyroid) offspring of hypothyroid mothers', 'In addition, TR cotransfection and treatment with the TRbeta1-selective agonist GC-1 suggested different functional coupling of the TR isoforms, TRbeta1 to transcription of beta-MyHC, SERCA, and TRbeta1,', 'dditionally, in T3-deprived samples alpha-sarcomeric actinin and SERCA-2 protein levels were reduced to 65.6 +/- 3% (P < 0.0001) and 74.1 +/- 4% (P=0.005), respectively, when compared with the T3-supplemented group.', 'even mild chronic myocardial thyrotoxicosis, such as may occur in human hyperthyroidism, can cause tachycardia and associated changes in high energy phosphate compounds independent of an increase in SERCA II and alpha-MHC.', 'Myocytes from banded hearts treated with T4 were hypertrophied but had increased concentrations of alpha-MHC and SERCA proteins', 'Thyroid hormone (T3) increases the transcription of the sarcoplasmic reticulum Ca2+ adenosine triphosphatase (ATPase) gene (SERCA 2) through three thyroid hormone response elements.', 'MEF-2a in combination with either T3R alpha 1 or T3R beta 1 isoforms resulted in a 2.5-fold increase in SERCA 2 transgene expression in the absence of T3. Addition of T3 did not induce any further increase in SERCA 2 expression when T3R alpha 1 and MEF-2a expression vectors were cotransfected. In contrast, in the presence of T3R beta 1 and MEF-2, the addition of T3 increased chlorampenicol acetyltransferase activity by an additional 2.2-fold to a total 5.5-fold increase.', 'Our findings point to T3R isoform-specific interactions with a cell type-specific transcription factor (MEF-2) in the regulation of SERCA 2 gene expression.', 'These data are consistent with pretranslational and possibly transcriptional level effect of thyroid hormone on the cardiac SR Ca2+ pump gene (SERCA 2)', '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.', 'Thyroid hormone receptor (TR), a transcriptional activator, affected the regulation of gene expression of MHC and SR Ca(2+)-ATPase.', 'The thyroid hormone responsiveness of SR Ca2(+)-ATPase mRNA has been previously established.', 'The mRNA encoding the sarcoplasmic reticulum (SR) Ca2+ ATPase is highly influenced by thyroid hormone (T3) in the hearts of intact animals.', 'Direct cellular effects of thyroid hormone have been implicated in modulating the expression of the myosin heavy chain (MHC) genes and the slow sarcoplasmic reticulum calcium adenosine triphosphatase (SR Ca(2+)-ATPase) gene.']
['The thyroid hormone (TH) induced regulation of  SERCA is mediated both by non-genomic and genomic actions.\nGenomic actions are mediated by the binding of T(3) receptors (TRs) to the thyroid response elements in the SERCA promotor and result in increased gene expression. \nThyroid hormone  increases the transcription of  SERCA 2  through three thyroid hormone response elements. \nData show that the regulation of  cardiac SERCA by thyroid hormone is made at the  pretranslational and possibly transcriptional level \nTRβ1 is shown to be coupled to the expression of SERCA in the heart\nAn  increase of TR expression in the hypertrophied heart has been show to result in  increased SERCA expression.\nInhibition of TRα1 by dronedarone does not change the expression of SERCA in the heart\nFindings show that  SERCA 2 gene expression  is regulated  by TR  isoform-specific interactions with transcription factor (MEF-2) \nHypothyroidism is accompanied by decreased expression of SERCA in the heart.   T3 increases expression of the cardiac SERCA\nTH treatment can reverse the reduction in the ratio of SERCA to phospholamban expression which is found in postinfarcted hearts\nTH treatment  results in increased expression of SERCA in hearts from banded rats']
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