The role of adrenergic system in regulation of cardiac myosin heavy chain gene expression.
The cardiac phenotype exhibits considerable plasticity, being under the regulation of numerous factors, such as developmental stage, functional load, as well as nutritional and hormonal states of the animal. Several lines of evidence indicate that the adrenergic nervous system plays an important role in the redistribution of myosin isoforms in the heart. For example, chemical sympathectomy favors the expression of V3 isomyosin at the expense of V1. In this study, we have examined the effect of adrenergic pathways on the expression of cardiac myosin heavy chain (MHC) genes. The level of cAMP was modulated by either adding forskolin or 8-bromo-cAMP to primary cultures of embryonic (18 d) cardiac myocytes. We have found that the level of mRNA coding for MHC-alpha was increased two- to three-fold. The effect was dose- and time-dependent and was potentiated further when the 8-Br-cAMP was given together with a phosphodiesterase inhibitor. The same changes were found in KCl arrested cells, indicating independence of contractile activity. Treatment of cells known to activate the protein kinase C (TPA) and inositol triphosphate pathways has increased the level of beta-MHC mRNA while that of alpha-MHC remained unchanged. These data lend strong support to direct effect of the adrenergic system on activity of cardiac genes.
Gupta
M P
MP
Department of Medicine, University of Chicago, Illinois.
Gupta
M
M
Zak
R
R
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D005333:Fetus; D015971:Gene Expression Regulation, Enzymologic; D006321:Heart / Q000187:drug effects*; D009218:Myosins / Q000235:genetics*; D010703:Phorbol Esters / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects* / Q000502:physiology; D015854:Up-Regulation
D010703:Phorbol Esters; D012333:RNA, Messenger; D011941:Receptors, Adrenergic; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000001:Calcimycin; D009218:Myosins