title: Cardiac myocyte terminal differentiation. Potential for cardiac regeneration.
abstract: The exact mechanism of terminal differentiation in cardiac myocytes is currently unknown. Studies in the skeletal muscle system provided a model where muscle lineage termination gene directly interacts with Rb to produce and maintain the terminally differentiated state. This interaction provided the critical components for the lock in cell cycle arrest in skeletal muscle cell. Cardiac muscle appears on the surface very similar to skeletal muscle especially since they share large numbers of structural and contractile proteins. However, it is clear that cardiac muscle cells are distinct biologically at the regulatory level. First and foremost, differentiation and capacity for hyperplasia (mitosis) is not mutually exclusive, in that the heart being the first functional organ embryologically is able to grow via cell division until shortly after birth. Thereafter further growth is provided by hypertrophy. In skeletal muscle, these two processes, differentiation and ability to undergo mitosis, appear to be mutually exclusive. Second, cardiac muscles have not been shown to express any of the skeletal muscle determination basic helix loop helix factors like myoD or any proteins that are functionally similar. Third, heterokaryons of cardiac myocytes and fibroblasts reveal a lack of dominance of the cardiac muscle phenotype. This is distinctly different in skeletal muscle, whose phenotype is dominant which provided a platform to identify the skeletal muscle determination gene, myoD. Although various basic helix loop helix proteins and homeobox genes have been identified in cardiac myocytes, their function remains to be elucidated. At this time no cardiac determination gene has been identified. Despite these differences, we have shown that the biology of pocket proteins Rb and P107 is similar in skeletal and cardiac myocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Cardiac Surgical Unit, Massachusetts General Hospital, Cambridge 02138, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: Tam
authors.forename: W
authors.initials: W
authors.lastname: Gu
authors.forename: V
authors.initials: V
authors.lastname: Mahdavi
authors.forename: B
authors.initials: B
authors.lastname: Nadal-Ginard
mesh_terms: D000818:Animals; D042846:CDC2-CDC28 Kinases; D006332:Cardiomegaly / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D002455:Cell Division; D019938:Cyclin D1; D056742:Cyclin D2; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis; D016213:Cyclins / Q000096:biosynthesis; D015870:Gene Expression; D016161:Genes, Retinoblastoma; D006321:Heart / Q000502:physiology*; D006801:Humans; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D015513:Oncogene Proteins / Q000096:biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis; D012038:Regeneration; D016160:Retinoblastoma Protein / Q000096:biosynthesis
chemical_list: C080336:CCND2 protein, human; D056742:Cyclin D2; D016213:Cyclins; D015513:Oncogene Proteins; D016160:Retinoblastoma Protein; D019938:Cyclin D1; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases