文章基本信息

标题：12(S)-Hydroperoxy-eicosatetraenoic acid increases arachidonic acid availability in collagen-primed platelets
本地全文：下载
作者：Catherine Calzada ; Evelyne Véricel ; Bérengère Mitel 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2001
卷号：42
期号：9
页码：1467-1473
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Lipid hydroperoxides have been reported to regulate cell function and eicosanoid formation. The aim of the present study was to determine the effect of 12( S )-hydroperoxy-eicosatetraenoic acid [12( S )-HPETE], the platelet 12-lipoxygenase-derived hydroperoxide of arachidonic acid (AA), on the availability of nonesterified AA, which represents a rate-limiting step in the biosynthesis of eicosanoids. The coincubation of human platelets with concentrations of 12( S )-HPETE below 50 nM and subthreshold concentrations (STC) of collagen (less than 0.24 μg/ml) significantly enhanced platelet aggregation and the formation of thromboxane B₂, the stable catabolite of the potent aggregating agent thromboxane A₂. In addition, the nonesterified endogenous AA concentration increased by 3-fold. Arachidonoyl-containing molecular species concentrations of 1,2-diacyl-glycero-3-phosphocholine, 1-alkyl-2-acyl-glycero-3-phosphocholine, and 1-alkenyl-2-acyl-glycero-3-phosphoethanolamine decreased specifically in response to 12( S )-HPETE, whereas no significant changes were observed within 1,2-diacyl-glycero-3-phosphoethanolamine and 1,2-diacyl-glycero-3-phosphoinositol molecular species. The 12( S )-HPETE-induced increase in nonesterified AA was fully prevented by arachidonoyl trifluoromethyl ketone, an inhibitor of cytosolic phospholipase A₂ (cPLA₂), and cPLA₂ was translocated to membranes and phosphorylated in platelets incubated with 12( S )-HPETE. In conclusion, these results indicate that nanomolar concentrations of 12( S )-HPETE could play a significant role in controlling the level of endogenous AA and the formation of thromboxane, thereby potentiating platelet function. —Calzada, C., E. Véricel, B. Mitel, L. Coulon, and M. Lagarde. 12( S )-Hydroperoxy-eicosatetraenoic acid increases arachidonic acid availability in collagen-primed platelets. J. Lipid Res. 2001. 42: 1467–1473.
关键词：cytosolic phospholipase A₂ ; hydroperoxides ; phospholipid molecular species ; platelet aggregation