Faculty Collaboration Database

The cAMP response element binding protein is expressed and phosphorylated in cardiac myocytes. Circ Res 1994 Jun;74(6):1042-9

Date

06/01/1994

Pubmed ID

8187274

DOI

10.1161/01.res.74.6.1042

Scopus ID

2-s2.0-0028321553 (requires institutional sign-in at Scopus site)   42 Citations

Abstract

Cardiac cells grow in response to a number of stimuli that activate intracellular signaling pathways. The cAMP-signaling pathway mediates the activation of gene transcription in other cell types by the cAMP response element binding protein (CREB-P). Our aim was to explore the physiological role of CREB-P in response to elevated cAMP in cardiac cells by determining if phosphorylation of CREB-P (to phosphoCREB-P) rapidly induces transcription in culture. Primary embryonic chick heart cultures were used in which cAMP was raised by forskolin (5 mumol/L) or isoproterenol (10 mumol/L) treatment. Since both these agents have inotropic effects, tension production was controlled with 2,3-butanedione monoxime (BDM). This allowed us to determine whether the cAMP-signaling pathway or the contractile state was regulating phosphorylation and transcription. The responses for time periods up to 2 hours were assayed with antibodies to detect phosphoCREB-P and by quantitative filter hybridization for creb gene expression. The staining intensity of the phosphoprotein increased in myocyte nuclei after 10 minutes and persisted for 1 hour with either forskolin or isoproterenol treatment. An increase in creb mRNA abundance was also detected, with the maximum level of expression being at 1 hour with forskolin treatment. These changes are independent of the contractile state, because BDM itself caused no change. BDM plus forskolin induced the same pattern of creb expression as observed with forskolin alone. Therefore, we conclude that elevation of cAMP leads to phosphorylation of CREB-P and an increase in creb mRNA abundance.

Author List

Goldspink PH, Russell B

MESH terms used to index this publication - Major topics in bold

Animals
Cells, Cultured
Chick Embryo
Colforsin
Cyclic AMP
Cyclic AMP Response Element-Binding Protein
Diacetyl
Gene Expression
Myocardium
Phosphorylation