The myocardial protein S100A1 plays a role in the maintenance of normal gene expression in the adult heart.
S100A1 and S100B are members of a family of 20 kDa Ca2+-binding homodimers that play a role in signal transduction in mammalian cells. S100A1 is the major isoform in normal heart and S100B, normally a brain protein, is induced in hypertrophic myocardium and functions as an intrinsic negative modulator of the hypertrophic response. In order to examine the function of S100A1, we first showed that, in contrast to S100B, S100A1 was downregulated in rat experimental models of myocardial hypertrophy following myocardial infarction or pressure overload. Second, in co-transfection experiments in cultured neonatal rat cardiac myocytes, S100A1 inhibited the alpha1-adrenergic activation of promoters of genes induced during the hypertrophic response including the fetal genes skeletal alpha actin (skACT), and beta-myosin heavy chain (MHC) and S100B, but not the triiodothyronine (T3) activation of the promoter of the alpha-MHC gene, that is normally expressed in adult myocardium. These results suggest that S100A1 is involved in the maintenance of the genetic program that defines normal myocardial function and that its downregulation is permissive for the induction of genes that underlie myocardial hypertrophy.
Tsoporis
James N
JN
The Centre for Cardiovascular Research, Division of Cardiology, Department of Medicine, The Toronto Hospital, University of Toronto, Toronto, ON, Canada.
Marks
Alexander
A
Zimmer
Danna B
DB
McMahon
Chris
C
Parker
Thomas G
TG
D000199:Actins / Q000235:genetics; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics; D032383:Myocytes, Cardiac / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D012333:RNA, Messenger; D009418:S100 Proteins