Phosphatidylinositol 4,5-bisphosphate regulates activation-induced platelet microparticle formation.
Phosphatidylinositol 4,5-bisphosphate regulates activation-induced platelet microparticle formation.
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磷脂酰肌醇 4,5-二磷酸调节激活诱导的血小板微粒形成。
DOI：
10.1021/bi047344c
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Flaumenhaft,Robert
中科院分区：
文献类型：
--
作者：
O'Connell,DanielJ;Rozenvayn,Nataliya;Flaumenhaft,Robert
While the role of the cytoskeleton in microparticle formation is well-described, the role of membrane phospholipids in regulating this process is poorly defined. PIP2binds many cytoskeletal proteins and may oppose microparticle formation through associations with these proteins. To determine whether PIP2effects microparticle formation, PIP2was incorporated into platelet membranes prior to activation-induced microparticle formation. Incorporation of PIP2into platelet membranes inhibited activation-induced microparticle formation by ≥90%. Inhibition was dose-dependent with an IC50of 12−18 μM. A permeabilized platelet system was next used to assess the effect of modulation of endogenous PIP2levels on microparticle formation. Infusion of type IIβ PIP kinase into permeabilized platelets inhibited microparticle formation by 75 ± 8%. In contrast, incubation of permeabilized platelets with PI-specific phospholipase C augmented microparticle formation by greater than 3-fold. Evaluation of PIP kinases following platelet activation demonstrated that they were lost from platelets in a calpain-dependent manner during microparticle formation. Purified μ-calpain cleaved recombinant type IIβ PIP kinase and inhibited its ability to phosphorylate PI(5)P. In permeabilized platelets, incubation of purified μ-calpain reduced PIP2levels, while exposure to calpeptin increased PIP2levels. Calpain has previously been implicated in platelet microparticle formation. These studies show that calpain may help limit PIP2formation following platelet activation and that PIP2content is an important determinant of platelet microparticle formation.
