Endothelin induction of inositol phospholipid hydrolysis, sarcomere assembly, and cardiac gene expression in ventricular myocytes. A paracrine mechanism for myocardial cell hypertrophy.
The present study examined the effects of endothelin-1 on phosphoinositide hydrolysis, diacylglycerol formation, and the induction of myocardial cell hypertrophy utilizing a well characterized cultured neonatal rat myocardial cell model. In this system, a hypertrophic response can be assessed by increases in myocardial cell size, an increase in the assembly of an individual contractile protein (myosin light chain-2) into organized contractile units, accumulation of contractile proteins, the activation of a program of immediate early gene expression, and the induction of genes encoding contractile and embryonic proteins (Iwaki, K., Sukhatme, V., Shubeita, H.E., Chien, K.R., (1990) J. Biol. Chem. 265, 13809-13817). Utilizing these criteria, the present study documents that stimulation with endothelin-1 can produce myocardial cell hypertrophy, induce the expression and release of ANF in ventricular cells, and can activate the transcription of cardiac-specific genes. In addition, endothelin-1 stimulates phosphoinositide hydrolysis and the accumulation of diacylglycerol. It is proposed that endothelin-1 stimulation may represent an important paracrine mechanism for the in vivo regulation of cardiac growth and hypertrophy.
Shubeita
H E
HE
Department of Medicine, University of California, San Diego, La Jolla 92093.
McDonough
P M
PM
Harris
A N
AN
Knowlton
K U
KU
Glembotski
C C
CC
Brown
J H
JH
Chien
K R
KR
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004075:Diglycerides / Q000378:metabolism; D016232:Endothelins / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D009218:Myosins / Q000235:genetics; D010716:Phosphatidylinositols / Q000378:metabolism*; D010957:Plasmids; D051381:Rats; D011919:Rats, Inbred Strains; D012518:Sarcomeres / Q000187:drug effects / Q000648:ultrastructure*
D004075:Diglycerides; D016232:Endothelins; D010716:Phosphatidylinositols; D009218:Myosins