Inhibitor analysis of LDL-induced platelet aggregation.
Oxidized low density lipoproteins (oxLDL) bounded to specific receptors on the platelet surface are able to activate platelets. However, the exact mechanism of signal transduction from LDL receptors into the cell still requires investigation. In the present paper inhibitors of the main enzymes of known platelet activation pathways were used to investigate the mechanism of the LDL-induced platelet aggregation. Our experiments were performed with autoxidized LDL (2-thiobarbituric acid reactive substances < 8 nmoles/mg). We demonstrated that the main enzymes of the arachidonate cycle do not play an important role in LDL-induced platelet aggregation, whereas inhibition of protein kinase C and phospholipase C--principal enzymes of the phosphoinositide cycle--resulted in the inhibition of LDL-induced platelet aggregation in a dose-dependent manner. It was also shown that transmembrane calcium transport was necessary for LDL-induced platelet activation. Thus, we conclude that the phosphoinositide cycle is the main mechanism of cellular signal transduction during LDL-induced platelet activation.
Vlasova
I I
II
Research Institute of Physical and Chemical Medicine, Moscow, Russia.
Azizova
O A
OA
Lopukhin YuM
D000098:Acetophenones / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D009637:Masoprocol / Q000494:pharmacology; D009355:Neomycin / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011973:Receptors, LDL / Q000378:metabolism; D015398:Signal Transduction; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D014700:Verapamil / Q000494:pharmacology
D000098:Acetophenones; D004791:Enzyme Inhibitors; D008077:Lipoproteins, LDL; D010716:Phosphatidylinositols; D010975:Platelet Aggregation Inhibitors; D011973:Receptors, LDL; D017392:Thiobarbituric Acid Reactive Substances; C099252:oxidized low density lipoprotein; D000244:Adenosine Diphosphate; D009637:Masoprocol; D014700:Verapamil; D011493:Protein Kinase C; D010738:Type C Phospholipases; D009355:Neomycin; C006821:4-bromophenacyl bromide; D002118:Calcium; D007213:Indomethacin