S100beta inhibits alpha1-adrenergic induction of the hypertrophic phenotype in cardiac myocytes.
In an experimental rat model of myocardial infarction, surviving cardiac myocytes undergo hypertrophy in response to trophic effectors. This response involves gene reprogramming manifested by the re-expression of fetal genes, such as the previously reported isoform switch from adult alpha- to embryonic beta-myosin heavy chain. We now report the transient re-expression of a second fetal gene, skeletal alpha-actin in rat myocardium at 7 days post-infarction, and its subsequent down-regulation coincident with the delayed induction of S100beta, a protein normally expressed in brain. In cultured neonatal rat cardiac myocytes, co-transfection with an S100beta-expression vector inhibits a pathway associated with hypertrophy, namely, alpha1-adrenergic induction of beta-myosin heavy chain and skeletal alpha-actin promoters mediated by beta-protein kinase C. The induction of beta-myosin heavy chain by hypoxia was similarly blocked by forced expression of S100beta. Our results suggest that S100beta may be an intrinsic negative regulator of the hypertrophic response of surviving cardiac myocytes post-infarction. Such negative regulators may be important in limiting the adverse consequences of unchecked hypertrophy leading to ventricular remodeling and dysfunction.
Tsoporis
J N
JN
The Centre for Cardiovascular Research, Division of Cardiology, Department of Medicine, The Toronto Hospital, University of Toronto, Toronto, Ontario M5G 2C4, Canada.
Marks
A
A
Kahn
H J
HJ
Butany
J W
JW
Liu
P P
PP
O'Hanlon
D
D
Parker
T G
TG
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001324:Autoantigens / Q000494:pharmacology*; D002135:Calcium-Binding Proteins / Q000494:pharmacology*; D006332:Cardiomegaly / Q000473:pathology*; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects; D009203:Myocardial Infarction / Q000473:pathology; D009206:Myocardium / Q000473:pathology*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D010641:Phenotype; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D015398:Signal Transduction
D000316:Adrenergic alpha-Agonists; D001324:Autoantigens; D002135:Calcium-Binding Proteins; D009414:Nerve Growth Factors; D018340:Receptors, Adrenergic, alpha-1; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D011493:Protein Kinase C