Induction of S100b in myocardium: an intrinsic inhibitor of cardiac hypertrophy.
Cardiac hypertrophy induced by pressure overload and following myocardial infarction entails regulation of myocardial gene expression, recapitulating an embryonic phenotype, including activation of fetal beta-myosin heavy chain and skeletal alpha-actin. Progressive hypertrophy and alterations in gene expression may contribute to myocardial failure. Although signaling pathways that contribute to hypertrophy development have been identified, intrinsic cardiac regulators that limit hypertrophic response have not been determined. The beta subunit of S100 protein is induced in the myocardium of human subjects and an experimental rat model following myocardial infarction. Forced S100 beta expression in neonatal rat cardiac myocyte cultures and high level expression of S100 beta in transgenic mice hearts inhibit cardiac hypertrophy and the associated phenotype by modulating protein kinase C-dependent pathways. S100 beta expression is probably a component of the myocyte response to trophic stimulation that serves as a negative feedback mechanism to limit cellular growth and the associated alterations in gene expression.
Toronto Hospital, ON, Canada.
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D000199:Actins / Q000235:genetics; D000818:Animals; D002303:Cardiac Output, Low / Q000209:etiology; D006332:Cardiomegaly / Q000209:etiology / Q000517:prevention & control*; D002455:Cell Division / Q000235:genetics; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005246:Feedback; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000150:complications; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000235:genetics; D024501:Nonmuscle Myosin Type IIB; D010641:Phenotype; D011493:Protein Kinase C / Q000235:genetics; D051381:Rats; D009418:S100 Proteins / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology
D000199:Actins; D009418:S100 Proteins; D011493:Protein Kinase C; D024501:Nonmuscle Myosin Type IIB; C103815:nonmuscle myosin type IIB heavy chain; D018995:Myosin Heavy Chains