Zhang J, Rittenhouse S E
Department of Pharmacology/Jefferson Cancer Institute, Philadelphia, PA, USA.
Biochem Biophys Res Commun. 1995 Jun 15;211(2):484-90. doi: 10.1006/bbrc.1995.1839.
Lysophosphatidic acid is a biologically active serum phospholipid known to have growth factor-like activities and to cause platelet aggregation. Activated phosphoinositide 3-kinase has been suggested to be involved in cytoskeletal reorganization and mitogenesis. We report that lysophosphatidic acid causes platelet phosphoinositide 3-kinase activation, leading to accumulation of phosphatidylinositol (3, 4, 5) P3 and phosphatidylinositol (3, 4) P2, and stimulates phospholipase C. Worthmannin, a potent inhibitor of phosphoinositide 3-kinase, blocks platelet aggregation induced by lysophosphatidic acid without impairing phospholipase C activation. Eristostatin, an antagonist of fibrinogen binding to platelet integrin, completely blocks platelet aggregation without inhibiting phosphoinositide 3-kinase or phospholipase C. We suggest that lysophosphatidic acid, in activating phosphoinositide 3-kinase, promotes platelet aggregation, but that platelet aggregation in response to lysophosphatidic acid does not significantly enhance phosphoinositide 3-kinase activation.
溶血磷脂酸是一种具有生物活性的血清磷脂，已知具有生长因子样活性并能引起血小板聚集。有研究表明，活化的磷脂酰肌醇3激酶参与细胞骨架重组和有丝分裂。我们报告称，溶血磷脂酸可导致血小板磷脂酰肌醇3激酶活化，进而导致磷脂酰肌醇（3,4,5）P3和磷脂酰肌醇（3,4）P2积累，并刺激磷脂酶C。渥曼青霉素是一种有效的磷脂酰肌醇3激酶抑制剂，可阻断溶血磷脂酸诱导的血小板聚集，而不影响磷脂酶C的活化。埃瑞他汀是一种纤维蛋白原与血小板整合素结合的拮抗剂，可完全阻断血小板聚集，而不抑制磷脂酰肌醇3激酶或磷脂酶C。我们认为，溶血磷脂酸在激活磷脂酰肌醇3激酶时促进血小板聚集，但溶血磷脂酸诱导的血小板聚集并不会显著增强磷脂酰肌醇3激酶的活化。
