Biomaterial Database

Inhibition of phosphatidic acid production and lysophospholipid formation in collagen-stimulated human platelets by staurosporine, a protein kinase inhibitor. 1991

L M Thomas, and B J Holub

Department of Nutritional Sciences, University of Guelph, Ontario, Canada.

To investigate a possible regulatory role of protein kinase C (PKC) on collagen-induced phospholipase activity, human platelets were prelabelled with either [3H] arachidonic acid or [14C]stearic acid and stimulated with collagen (2 micrograms/ml) in the presence or absence of the protein kinase inhibitor, staurosporine (1 microM). The collagen-induced release of [3H]arachidonic acid and formation of [14C]stearoyl-labelled lysophospholipids was inhibited by prior incubation with staurosporine, as was the formation of 3H-labelled thromboxane B2, thereby suggesting inhibition of the collagen-induced phospholipase A2 activity. The degradation of phosphatidylinositol (PI) and elevation of phosphatidic acid (PA) in platelets prelabelled with either radiotracer were also completely blocked by staurosporine pretreatment, indicating a suppression of collagen-stimulated phospholipase C activity. Suppressed phospholipase C activity may have been due to diminished thromboxane A2 formation since treatment with the dual cyclo-oxygenase/lipoxygenase inhibitor, BW755C, also resulted in an inhibition of the collagen-stimulated loss of 14C-labelled PI and rise in PA by 75-80%. Our results suggest that protein kinase, possible PKC, may be involved in the regulation of these phospholipases in collagen-stimulated human platelets.

UI	MeSH Term	Description	Entries
D008246	Lysophospholipids	Derivatives of PHOSPHATIDIC ACIDS that lack one of its fatty acyl chains due to its hydrolytic removal.	Lysophosphatidic Acids,Lysophospholipid,Acids, Lysophosphatidic
D010712	Phosphatidic Acids	Fatty acid derivatives of glycerophosphates. They are composed of glycerol bound in ester linkage with 1 mole of phosphoric acid at the terminal 3-hydroxyl group and with 2 moles of fatty acids at the other two hydroxyl groups.	Ammonium Phosphatidate,Diacylglycerophosphates,Phosphatidic Acid,Acid, Phosphatidic,Acids, Phosphatidic,Phosphatidate, Ammonium
D010738	Type C Phospholipases	A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC 3.1.4.3), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.	Lecithinase C,Phospholipase C,Phospholipases, Type C,Phospholipases C
D010741	Phospholipases A	Phospholipases that hydrolyze one of the acyl groups of phosphoglycerides or glycerophosphatidates.
D011450	Prostaglandin Endoperoxides, Synthetic	Synthetic compounds that are analogs of the naturally occurring prostaglandin endoperoxides and that mimic their pharmacologic and physiologic activities. They are usually more stable than the naturally occurring compounds.	Prostaglandin Endoperoxide Analogs,Prostaglandin Endoperoxide Analogues,Synthetic Prostaglandin Endoperoxides,Analogues, Prostaglandin Endoperoxide,Endoperoxide Analogues, Prostaglandin,Endoperoxides, Synthetic Prostaglandin
D001792	Blood Platelets	Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation.	Platelets,Thrombocytes,Blood Platelet,Platelet,Platelet, Blood,Platelets, Blood,Thrombocyte
D003094	Collagen	A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).	Avicon,Avitene,Collagen Felt,Collagen Fleece,Collagenfleece,Collastat,Dermodress,Microfibril Collagen Hemostat,Pangen,Zyderm,alpha-Collagen,Collagen Hemostat, Microfibril,alpha Collagen
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000470	Alkaloids	Organic nitrogenous bases. Many alkaloids of medical importance occur in the animal and vegetable kingdoms, and some have been synthesized. (Grant & Hackh's Chemical Dictionary, 5th ed)	Alkaloid,Plant Alkaloid,Plant Alkaloids,Alkaloid, Plant,Alkaloids, Plant
D001095	Arachidonic Acids		Eicosatetraenoic Acids,Acids, Arachidonic,Acids, Eicosatetraenoic