Regulation and functional significance of phospholipase D in myocardium

  • Yvonne E. G. Eskildsen-Helmond
  • Han A. A. Van Heugten
  • Jos M. J. Lamers
Chapter
Part of the Developments in Molecular and Cellular Biochemistry book series (DMCB, volume 17)

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 II that are shown to activate phospholipase D, also potently stimulate phospholipase C-β 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.

Key words

phospholipase D signaltransduction myocardium cardiomyocytes protein kinase C phospholipase C phosphatidic acid phosphatidylethanol hypertrophy ischemic preconditioning inotrophy 

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Copyright information

© Kluwer Academic Publishers 1996

Authors and Affiliations

  • Yvonne E. G. Eskildsen-Helmond
    • 1
  • Han A. A. Van Heugten
    • 1
  • Jos M. J. Lamers
    • 1
  1. 1.Department of Biochemistry, Cardiovascular Research Institute (COEUR), Faculty of Medicine and Health SciencesErasmus University RotterdamRotterdamThe Netherlands

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