S100A6 is a negative regulator of the induction of cardiac genes by trophic stimuli in cultured rat myocytes.
S100A6 (calcyclin), a member of the S100 family of EF-hand Ca2+ binding proteins, has been implicated in the regulation of cell growth and proliferation. We have previously shown that S100B, another member of the S100 family, is induced postinfarction and limits the hypertrophic response of surviving cardiac myocytes. We presently report that S100A6 expression is also increased in the periinfarct zone of rat heart postinfarction and in cultured neonatal rat myocytes by treatment with several trophic agents, including platelet-derived growth factor (PDGF), the alpha1-adrenergic agonist phenylephrine (PE), and angiotensin II (AII). Cotransfection of S100A6 in cultured neonatal rat cardiac myocytes inhibits induction of the cardiac fetal gene promoters skeletal alpha-actin (skACT) and beta-myosin heavy chain (beta-MHC) by PDGF, PE, AII, and the prostaglandin F2alpha (PGF2alpha), induction of the S100B promoter by PE, and induction of the alpha-MHC promoter by triiodothyronine (T3). By contrast, S100B cotransfection selectively inhibited only PE induction of skACT and beta-MHC promoters. Fluorescence microscopy demonstrated overlapping intracellular distribution of S100B and S100A6 in transfected myocytes and in postinfarct myocardium but heterodimerization of the two proteins could not be detected by co-immunoprecipitation. We conclude that S100A6 may function as a global negative modulator of differentiated cardiac gene expression comparable to its putative role in cell cycle progression of dividing cells.
Tsoporis
J N
JN
Department of Medicine, Division of Cardiology, University of Toronto, St. Michael's Hospital, Room 6-044, Queen Wing, 30 Bond Street, Toronto, Ontario, M5B 1W8, Canada.
Marks
A
A
Haddad
A
A
O'Hanlon
D
D
Jolly
S
S
Parker
T G
TG
D000199:Actins / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009414:Nerve Growth Factors; D010656:Phenylephrine / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D000075383:S100 Calcium Binding Protein A6; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D024723:Ventricular Myosins / Q000235:genetics
D000199:Actins; D018797:Cell Cycle Proteins; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D000075383:S100 Calcium Binding Protein A6; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C489132:S100a6 protein, rat; C579158:S100b protein, rat; D010656:Phenylephrine; D004247:DNA; D024723:Ventricular Myosins