Mechanism of activation of ADP-induced platelet aggregation under the influence of oxidatively modified fibrinogen.
For evaluation of the mechanisms underlying the effect of oxidized fibrinogen on platelet aggregation we studied ADP-induced platelet aggregation in the presence of UV-oxidized fibrinogen and inhibitors of major enzymes of platelet activation. Cyclooxygenase inhibitor acetylsalicylic acid, protein kinase C inhibitor H7, and to a lesser extent, protein tyrosine kinase inhibitor genistein suppressed ADP-induced platelet aggregation. In the presence of oxidized fibrinogen the degree of suppression was lower than in the presence of nonoxidized fibrinogen. Phospholipase C inhibitor U73122 markedly suppressed platelet aggregation in the presence of oxidized and nonoxidized fibrinogen. It can be hypothesized that oxidized fibrinogen activates platelets by modulating activity of the key signal component phospholipase C.
Aseichev
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AV
Laboratory for Biophysical Basics of Pathology, Institute of Physicochemical Medicine, Russian Ministry of Health, Moscow. aseychev@mail.ru
Azizova
O A
OA
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005340:Fibrinogen / Q000737:chemistry / Q000494:pharmacology* / Q000528:radiation effects; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D010084:Oxidation-Reduction; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011760:Pyrrolidinones / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D014466:Ultraviolet Rays
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D004963:Estrenes; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D000244:Adenosine Diphosphate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D005340:Fibrinogen; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D010738:Type C Phospholipases; D001241:Aspirin