Apoptosis in cardiac diseases: stress- and mitogen-activated signaling pathways.
Apoptosis is a form of cell death that involves discrete genetic and molecular programs, de novo protein expression and a unique cellular phenotype. Evidence for the existence of apoptosis in the human heart has been reported in various cardiac diseases, including ischemic and non-ischemic heart failure, myocardial infarction and arrhythmias. Among the most potent stimuli that elicit cardiomyocyte apoptosis are: oxygen radicals (including NO), cytokines (FAS/TNF alpha-receptor signaling), stress conditions (chemical or physical, e.g., radiation), sphingolipid metabolites (ceramide) and autocoids, e.g., angiotensin II. Apoptosis of cardiac myocytes may contribute to progressive pump-failure, arrhythmias and cardiac remodeling. The recognition of numerous molecular targets associated with cardiomyocyte apoptosis may provide novel therapeutic strategies for diverse cardiac ailments, as recently suggested by pharmacologic studies in experimental animals. This review paper is aimed to highlight the role of protein kinase signaling pathways in apoptosis with special attention to the stress-activated protein kinases (SAPK) and mitogen-activated protein kinases (MAPK) systems.
Feuerstein
G Z
GZ
Cardiovascular Disease Research, DuPont Pharmaceuticals Corporation, Wilmington, DE 19880-0400, USA.
Young
P R
PR
D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D020935:MAP Kinase Signaling System; D009206:Myocardium / Q000378:metabolism*; D018384:Oxidative Stress; D010743:Phospholipids / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D015290:Second Messenger Systems
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D010743:Phospholipids; D011494:Protein Kinases