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Studies on the function and the regulation of expression of platelet membrane protein GPIV (CD36)

血小板膜蛋白GPIV（CD36）的功能及表达调控研究

基本信息

批准号：
09672346
负责人：
HAYASHI Yukiko
金额：
$ 2.05万
依托单位：
Asahikawa Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09672346/
关键词：
Platlet Signal transduction PKC Arachidonic acid CD36 PUFA 膜蛋白CD36 多価不飽和脂肪酸

项目摘要

We have studied the effects of platelet membrane protein CD36 on the platelet signal transduction using CD36 defective platelets. One of the reported roles of CD36 is the transporter of unsaturated fatty acids. Compared to normal ones little characteristic responses of CD36 defective platelets have been reported. Arachidonic acid (AA), one of the unsaturated fatty acid, has pivotal role in platelet aggregation through its metabolite TxA2. We observed that under the decreasing store Ca2+ conditions CD36 defective platelets showed clear differences in the reactions where AA metabolites have more essential roles. We found that AA inhibits platelet aggregation induced by its metabolites TxA2. The IC50 of AA for normal platelets was 26.5±12.2 μM,and that for C36 defective platelets was 105±44 μM respectively. These results corroborate the role of CD36 as fatty acid transporter. This is the first report on the impaired functions of CD36 defective platelets. AA and other unsaturated fatty acids activate Ca2+ independent PKC in the cytosol independently of membrane lipids and cytosolic Ca2+ Physiological significances of the PKC isotypes have not been clearly understood. Hence the mechanisms of the inhibiting effects of AA were next studied. It was confirmed that AA inhibits PLCβ activation through serine phosphorylation by Ca2+ independent PKC.Consequently the Ca2+ dependent PKC closely connected to aggregation are not activated. Thus PKC isotypes are linked to each other leading to the physiologically proper responses of platelets. More important point is that AA itself regulates reactions induced by its descendants through the PKC isotypes.

我们用CD 36缺陷的血小板研究了血小板膜蛋白CD 36对血小板信号转导的影响。报道的CD 36的作用之一是不饱和脂肪酸的转运蛋白。与正常血小板相比，CD 36缺陷血小板的特征性反应很少。花生四烯酸（AA）是一种不饱和脂肪酸，通过其代谢产物TxA 2在血小板聚集中发挥重要作用。我们观察到，在储存Ca 2+减少的条件下，CD 36缺陷型血小板在AA代谢物具有更重要作用的反应中表现出明显的差异。我们发现AA抑制其代谢产物TxA 2诱导的血小板聚集。AA对正常血小板的IC_（50）为26.5±12.2 μM，对C36缺陷血小板的IC_（50）为105±44 μM。这些结果证实了CD 36作为脂肪酸转运蛋白的作用。这是首次报道CD 36缺陷型血小板功能受损。AA和其它不饱和脂肪酸激活胞质中的不依赖于Ca ~（2+）的PKC，而不依赖于膜脂和胞质Ca ~（2+）。因此，AA的抑制作用的机制进行了研究。结果表明，AA通过Ca ~（2+）非依赖性PKC的丝氨酸磷酸化抑制PLCβ的活化，从而使与聚集密切相关的Ca ~（2+）依赖性PKC不被激活。因此，PKC同种型彼此连接，导致血小板的生理学上适当的反应。更重要的一点是，AA本身通过PKC同种型调节其后代诱导的反应。