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.

我们使用 CD36 缺陷血小板研究了血小板膜蛋白 CD36 对血小板信号转导的影响，已报道的 CD36 的作用之一是不饱和脂肪酸的转运蛋白，与正常的相比，CD36 缺陷血小板的特征性反应很少有报道。花生四烯酸 (AA) 是一种不饱和脂肪酸，通过其代谢物 TxA2 在血小板聚集中发挥关键作用。我们观察到，在钙储存减少的条件下。 CD36缺陷血小板的反应表现出明显的差异，其中AA代谢物具有更重要的作用，我们发现AA抑制其代谢物TxA2诱导的血小板聚集，AA对正常血小板的IC50为26.5±12.2μM，而对C36缺陷血小板的IC50为26.5±12.2μM。分别为 105±44 μM 这些结果证实了 CD36 作为脂肪酸转运蛋白的作用。 AA 和其他不饱和脂肪酸可独立于膜脂质和胞质 Ca2+ 激活细胞质中的 Ca2+ 独立 PKC。 PKC 同种型的生理意义尚未明确，因此 AA 的抑制作用机制尚不清楚。接下来的研究证实AA通过Ca2+非依赖性PKC的丝氨酸磷酸化来抑制PLCβ激活。因此Ca2+依赖性PKC密切相关。与聚集相关的蛋白未被激活，因此 PKC 同种型彼此相连，从而导致血小板的生理学正确反应。更重要的是，AA 本身通过 PKC 同种型调节其后代诱导的反应。