The roles of protein kinase C and intracellular Ca2+ in the secretion of von Willebrand factor from human vascular endothelial cells
Open Access
- 1 September 1992
- journal article
- Published by Portland Press Ltd. in Biochemical Journal
- Vol. 286 (2) , 631-635
- https://doi.org/10.1042/bj2860631
Abstract
Secretion of von Willebrand factor (vWf) glycoprotein from storage granules in human umbilical-vein endothelial cells was studied in vitro. Either elevation of intracellular Ca2+ concentration ([Ca2+]i) with a Ca2+ ionophore or activation of protein kinase (PK) C by phorbol 12-myristate 13-acetate caused vWf secretion, and together the agents acted synergistically. However, when vWf release was stimulated by receptor-mediated agonists, selective inhibition of PKC had no effect on histamine-induced secretion and significantly elevated thrombin-induced secretion. Furthermore, ATP, which efficiently elevates [Ca2+]i in these cells, was a very poor effector of vWf release. We conclude that elevation of [Ca2+]i by physiological agonists is necessary for vWf release, but other signalling mechanisms, as yet uncharacterized, but not due to PKC activation, are required for full induction of the secretory pathway.Keywords
This publication has 26 references indexed in Scilit:
- Potent selective inhibitors of protein kinase CFEBS Letters, 1989
- Desensitization of inositol phosphate production after agonist stimulation of endothelial cells is not mediated by protein kinase CBiochemical and Biophysical Research Communications, 1989
- Thrombin and histamine activate phospholipase C in human endothelial cells via a phorbol ester‐sensitive pathwayJournal of Cellular Physiology, 1988
- Perturbation of cultured human vascular endothelial cells by phorbol ester or thrombin alters the cellular von Willebrand factor distributionJournal of Cellular Physiology, 1987
- Changes in cytosolic Ca2+ associated with von Willebrand factor release in human endothelial cells exposed to histamine. Study of microcarrier cell monolayers using the fluorescent probe indo-1.Journal of Clinical Investigation, 1987
- Fibrin induces release of von Willebrand factor from endothelial cells.Journal of Clinical Investigation, 1987
- Inducible secretion of large, biologically potent von Willebrand factor multimersCell, 1986
- Isolation of a storage and secretory organelle containing Von Willebrand protein from cultured human endothelial cellsBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1984
- Variant von Willebrand's DiseaseJournal of Clinical Investigation, 1980
- Culture of Human Endothelial Cells Derived from Umbilical Veins. IDENTIFICATION BY MORPHOLOGIC AND IMMUNOLOGIC CRITERIAJournal of Clinical Investigation, 1973