Platelet activation by simultaneous actions of diacylglycerol and unsaturated fatty acids.
Several cis-unsaturated fatty acids such as oleic, linoleic, linolenic, eicosapentaenoic, and docosahexaenoic acids added directly to intact human platelets greatly enhance protein kinase C activation as judged by the phosphorylation of its specific endogenous substrate, a 47-kDa protein. This enhancement absolutely requires the presence of a membrane-permeant diacylglycerol, 1,2-dioctanoylglycerol, or a tumor-promoting phorbol ester, phorbol 12-myristate 13-acetate. In the presence of ionomycin and either 1,2-dioctanoylglycerol or phorbol 12-myristate 13-acetate, the release of serotonin from the platelets is also remarkably increased by cis-unsaturated fatty acids. The effect of these fatty acids is observed at concentrations less than 50 microM. Saturated fatty acids and trans-unsaturated fatty acids are inactive. Titration of ionomycin to induce a release reaction and measurement of the intracellular Ca2+ level by the fura-2 procedure indicate that cis-unsaturated fatty acids increase an apparent sensitivity of the platelet response to Ca2+. The results suggest that cis-unsaturated fatty acids, which are presumably produced from phosphatidylcholine by signal-dependent activation of phospholipase A2, may take part directly in cell signaling through the protein kinase C pathway.
Yoshida
K
K
Department of Biochemistry, Kobe University School of Medicine, Japan.
Asaoka
Y
Y
Nishizuka
Y
Y
D004075:Diglycerides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D015759:Ionomycin / Q000494:pharmacology; D007700:Kinetics; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D015539:Platelet Activation / Q000187:drug effects*; D011493:Protein Kinase C / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism; D013329:Structure-Activity Relationship; D013997:Time Factors
D004075:Diglycerides; D005230:Fatty Acids, Nonesterified; D010750:Phosphoproteins; D012701:Serotonin; D015759:Ionomycin; D011493:Protein Kinase C