Regulation and functional significance of phospholipase D in myocardium |
| |
Authors: | Yvonne E G Eskildsen-Helmond Han A A Van Heugten Jos M J Lamers |
| |
Institution: | (1) Department of Biochemistry, Cardiovascular Research Institute (COEUR), Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, P.O. Box 1738, 3000 DR, Rotterdam, The Netherlands |
| |
Abstract: | There is now clear evidence that receptor-dependent phospholipase D is present in myocardium. This novel signal transduction pathway provides an alternative source of 1,2-diacylglycerol, which activates isoforms of protein kinase C. The members of the protein kinase C family respond differently to various combinations of Ca2+, phosphatidylserine, molecular species of 1,2-diacylglycerol and other membrane phospholipid metabolites including free fatty acids. Protein kinase C isozymes are responsible for phosphorylation of specific cardiac substrate proteins that may be involved in regulation of cardiac contractility, hypertrophic growth, gene expression, ischemic preconditioning and electrophysiological changes. The initial product of phospholipase D, phosphatidic acid, may also have a second messenger role. As in other tissues, the question how the activity of phospholipase D is controlled by agonists in myocardium is controversial. Agonists, such as endothelin-1, atrial natriuretic factor and angiotensin 11 that are shown to activate phospholipase D, also potently stimulate phospholipase C- in myocardium. PMA stimulation of protein kinase C inactivates phospholipase C and strongly activates phospholipase D and this is probably a major mechanism by which agonists that promote phosphatidyl-4,5-bisphosphate hydrolysis secondary activate phosphatidylcholine-hydrolysis. On the other hand, one group has postulated that formation of phosphatidic acid secondary activates phosphatidyl-4,5-bisphosphate hydrolysis in cardiomyocytes. Whether GTP-binding proteins directly control phospholipase D is not clearly established in myocardium. Phospholipase D activation may also be mediated by an increase in cytosolic free Ca2+ or by tyrosine-phosphorylation. |
| |
Keywords: | phospholipase D signaltransduction myocardium cardiomyocytes protein kinase C phospholipase C phosphatidic acid phosphatidylethanol hypertrophy ischemic preconditioning inotropy |
本文献已被 SpringerLink 等数据库收录! |
|