Different Requirement of Intracellular Calcium and Protein Kinase C for Arachidonic Acid Release and Serotonin Secretion in Cathepsin G-activated Platelets

Summary Previous studies have shown that platelet stimulation with cathepsin G rapidly results in cytoplasmic calcium ([Ca2+]j) increase and activation of protein kinase C (PKC). To elucidate the relationship between these two biochemical events and their relative contribution to the regulation of platelet response to cathepsin G, arachidonic acid (AA) release and serotonin (5HT) secretion were studied. Platelets made Ca2+- depleted and -permeable by treatment with A23187 were compared to intact platelets to better dissociate calcium changes from other receptor- stimulated events. AA release elicited by cathepsin G in intact platelets was prevented by the Ca2+ chelator BAPTA; in Ca2+-depleted, -permeable platelets AA was released in direct response to added Ca2+ and was not increased by simultaneous stimulation with cathepsin G. In intact platelets, PKC inhibition by Ro 31-8220 or PKC induction with PMA either enhanced or reduced, respectively, cathepsin G-induced AA release. Both BAPTA and Ro 31-8220 prevented 5HT secretion from intact platelets; however, in Ca2+-depleted, -permeable platelets, cathepsin G was able to evoke 5HT secretion and p47 phosphorylation independently of [Ca2+]j increase, both effects being hampered by Ro 31-8220. Ca2+ and PKC therefore regulate PLA2 activity and 5HT secretion in cathepsin G-stimulated platelets in a different manner: the former is mainly triggered by [Ca2+]j increase, while PKC represents the major factor in determining dense granule secretion.

[1]  R. Farndale,et al.  lonomycin-stimulated Arachidonic Acid Release in Human Platelets: a Role for Protein Kinase C and Tyrosine Phosphorylation , 1996, Thrombosis and Haemostasis.

[2]  P. Renesto,et al.  The phospholipase C/protein kinase C pathway is involved in cathepsin G-induced human platelet activation: comparison with thrombin. , 1996, The Biochemical journal.

[3]  A. Marcus,et al.  Thrombosis and Inflammation as Multicellular Processes: Significance of Cell-Cell Interactions , 1995, Thrombosis and Haemostasis.

[4]  C. Cerletti,et al.  Platelet Activation by Polymorphonuclear Leukocytes: Role of Cathepsin G and P-Selectin , 1995, Thrombosis and Haemostasis.

[5]  R. Farndale,et al.  The Tyrosine Kinase Inhibitors, Genistein and Methyl 2,5-Dihydroxycinnamate, Inhibit the Release of (3H)Arachidonate from Human Platelets Stimulated by Thrombin or Collagen , 1994, Thrombosis and Haemostasis.

[6]  C. Cerletti,et al.  Polymorphonuclear Leukocyte-Platelet Interaction: Role of P-Selectin in Thromboxane B2 and Leukotriene C4 Cooperative Synthesis , 1994, Thrombosis and Haemostasis.

[7]  L. Salvatore,et al.  Neutrophil Derived Cathepsin G Induces Potentially Thrombogenic Changes in Human Endothelial Cells: a Scanning Electron Microscopy Study in Static and Dynamic Conditions , 1994, Thrombosis and Haemostasis.

[8]  M. Selak.  Cathepsin G and thrombin: evidence for two different platelet receptors. , 1994, The Biochemical journal.

[9]  C. Cerletti,et al.  Effects of leukocyte-derived cathepsin G on platelet membrane glycoprotein Ib-IX and IIb-IIIa complexes: a comparison with thrombin. , 1993, Blood.

[10]  Roger J. Davis,et al.  cPLA2 is phosphorylated and activated by MAP kinase , 1993, Cell.

[11]  C. Cerletti,et al.  Intracellular Ca2+ rise in human platelets induced by polymorphonuclear-leucocyte-derived cathepsin G. , 1992, The Biochemical journal.

[12]  R. Faint.  Platelet-neutrophil interactions: their significance. , 1992, Blood reviews.

[13]  J. White,et al.  Platelet activation by fMLP-stimulated polymorphonuclear leukocytes: the activity of cathepsin G is not prevented by antiproteinases. , 1991, Blood.

[14]  P. Parker,et al.  Protein kinase C heterogeneity in GH4C1 rat pituitary cells. Characterization of a Ca2(+)-independent phorbol ester receptor. , 1990, The Journal of biological chemistry.

[15]  P. Renesto,et al.  Activation of human platelets by C5a-stimulated neutrophils: a role for cathepsin G. , 1990, The American journal of physiology.

[16]  P. Renesto,et al.  Interference of recombinant eglin C, a proteinase inhibitor extracted from leeches, with neutrophil-mediated platelet activation. , 1990, Laboratory investigation; a journal of technical methods and pathology.

[17]  M. Selak,et al.  Cathepsin G binding to human platelets. Evidence for a specific receptor. , 1990, The Biochemical journal.

[18]  Kuo-ping Huang,et al.  The mechanism of protein kinase C activation , 1989, Trends in Neurosciences.

[19]  P. Davis,et al.  Potent selective inhibitors of protein kinase C , 1989, FEBS letters.

[20]  M. Kroll,et al.  Biochemical mechanisms of platelet activation. , 1989, Blood.

[21]  M. Tyers,et al.  Molecular cloning and expression of the major protein kinase C substrate of platelets , 1988, Nature.

[22]  M. Chignard,et al.  Cathepsin G is a strong platelet agonist released by neutrophils. , 1988, The Biochemical journal.

[23]  K. Glaser,et al.  Regulation of eicosanoid biosynthesis in vitro and in vivo by the marine natural product manoalide: a potent inactivator of venom phospholipases. , 1988, The Journal of pharmacology and experimental therapeutics.

[24]  S. P. Halenda,et al.  Thrombin and C-kinase activators potentiate calcium-stimulated arachidonic acid release in human platelets. , 1987, The Biochemical journal.

[25]  Y. Nishizuka.  Studies and perspectives of protein kinase C. , 1986, Science.

[26]  P. Cuatrecasas,et al.  A model for intracellular translocation of protein kinase C involving synergism between Ca2+ and phorbol esters , 1985, Nature.

[27]  S. P. Halenda,et al.  Phorbol myristate acetate inhibits thrombin-stimulated Ca2+ mobilization and phosphatidylinositol 4,5-bisphosphate hydrolysis in human platelets. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[28]  R. Tsien,et al.  A new generation of Ca2+ indicators with greatly improved fluorescence properties. , 1985, The Journal of biological chemistry.

[29]  H. Hidaka,et al.  Phorbol ester-induced activation of human platelets is associated with protein kinase C phosphorylation of myosin light chains , 1983, Nature.

[30]  S. Watson,et al.  Synergy between Ca2+ and protein kinase C is the major factor in determining the level of secretion from human platelets. , 1993, The Biochemical journal.

[31]  Y. Nomura,et al.  Modes of inhibitory action of 4 beta-phorbol 12-myristate 13-acetate in thrombin-stimulated arachidonic acid release in intact and permeabilized platelets. , 1990, Archives of biochemistry and biophysics.

[32]  P. Henson.  Interactions between neutrophils and platelets. , 1990, Laboratory investigation; a journal of technical methods and pathology.

[33]  J. Weinberg,et al.  Receptor-mediated modulation of human monocyte, neutrophil, lymphocyte, and platelet function by phorbol diesters. , 1982, The Journal of clinical investigation.

[34]  A. Fabiato,et al.  Calculator programs for computing the composition of the solutions containing multiple metals and ligands used for experiments in skinned muscle cells. , 1979, Journal de physiologie.