Gq signaling in cardiac adaptation and maladaptation.
Accumulating evidence suggests that cardiac responses to a number of circulating or locally released humoral factors contribute to adaptive responses after hemodynamic stress or myocardial injury. In particular, hormones such as angiotensin II, endothelin 1, norepinephrine and prostaglandin F2 alpha which bind to and activate cardiomyocyte membrane receptors coupled to the Gq class of GTP binding proteins have been implicated in the development and ultimate decompensation of cardiac hypertrophy. Herein we summarize recent developments in cultured cardiomyocyte and transgenic mouse systems which are defining the phenotypes resulting from Gq signaling events in cardiomyocytes, and which are elucidating the critical downstream mediators. Postulated roles for protein kinase C, p38 MAP kinase and jun-N terminal kinase are discussed in relation to Gq-mediated cardiomyocyte hypertrophy and apoptotic signaling. The evidence to date suggests that molecular targeting of Gq or its effectors has the potential to modify cardiac adaptive and maladaptive responses to stress or injury.
Dorn
G W
GW
Department of Medicine, University of Cincinnati College of Medicine, Ohio 45267, USA.
Brown
J H
JH
D000222:Adaptation, Physiological / Q000502:physiology*; D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology; D006332:Cardiomegaly / Q000503:physiopathology; D002478:Cells, Cultured; D015237:Dinoprost / Q000502:physiology; D019332:Endothelin-1 / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology*; D006321:Heart / Q000502:physiology*; D006331:Heart Diseases / Q000503:physiopathology*; D006439:Hemodynamics / Q000502:physiology; D048031:JNK Mitogen-Activated Protein Kinases; D051379:Mice; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases; D009206:Myocardium / Q000166:cytology; D009638:Norepinephrine / Q000502:physiology; D010641:Phenotype; D011493:Protein Kinase C / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases
D019332:Endothelin-1; D000804:Angiotensin II; D015237:Dinoprost; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins; D009638:Norepinephrine