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Effect of aging and neurodegenerative disorders on cellular membrane fluidity

衰老和神经退行性疾病对细胞膜流动性的影响

基本信息

批准号：
01570517
负责人：
SAKAKIHARA Yoichi
金额：
$ 1.34万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1991
项目状态：
已结题

项目摘要

The physiological properties of cellular membrane have determined many important cellular function by regulating cell motility, adhesion to the substrate, and the affinity of receptor to the ligands. The membrane fluidity is one of such physiological properties of cellular membrane, and has been studied extensively. We have measured the membrane fluidity of platelet in patients with neurodegenerative disorders, since platelet membrane shares many receptors with neurons and could be a good model to probe the changes in neuronal function.We used steady state anisotropy of a lipophilic membrane probe, diphenylhexatrien, to monitor the changes in membrane fluidity. Using this probe, we measured the membrane fluidity of the platelet derived from patients with Alzheimer disease and Rett syndrome. It was found that the membrane fluidity in the platelet derived from the patients with Alzheimer disease was higher (more fluid) than those from age matched control. Recently, it was found that apop … More rotein E in patients with Alzheimer disease is abnormal. The abnormal increase in platelet membrane fluidity might be relevant to apoprotein abnormality. The membrane fluidity of platelet from Rett syndrome was not different from the control.Since the lipid environment of platelet might alter their membrane fluidity, we next investigated the effect of plasma triglyceride on platelet membrane fluidity. We incubated human platelet with high concentration of triglyceride emulsion. It was clearly shown that the presence of triglyceride in the incubation medium has increased platelet membrane fluidity. In order to further delineate the mechanism of triglyceride action on platelet membrane, we measured the content of cholesterol in the platelet membrane. Cholesterol is one of the major determinant of cellular membrane fluidity along with fatty acid carbon chain length. It was shown that platelet membrane cholesterol decreased when the platelet were incubated with high concentration of triglyceride.As mentioned earlier, platelet membrane shares many receptors with neuronal plasma membrane. The altered lipid environments as happened in some inborn errors of lipid metabolism, might alter membrane properties of neuron, and thus changes neuronal function.It is implicated that measuring platelet membrane fluidity could give us important information on the function of neuronal membrane as well. Less

细胞膜的生理特性通过调节细胞运动、与底物的粘附以及受体与配体的亲和力来决定细胞的许多重要功能。细胞膜流动性是细胞膜的重要生理特性之一，已被广泛研究。我们测定了神经退行性疾病患者的血小板膜流动性，因为血小板膜与神经元有许多共同的受体，可以是一个很好的模型来探测神经元功能的变化，我们使用稳态各向异性的亲脂性膜探针，二苯基己三烯，监测膜流动性的变化。用此探针测定了阿尔茨海默病和Rett综合征患者血小板的膜流动性。结果发现，阿尔茨海默病患者血小板膜流动性高于同龄对照组。最近，人们发现， ...更多信息阿尔茨海默病患者的鱼藤素E异常。血小板膜流动性异常增高可能与载脂蛋白异常有关。Rett综合征患者的血小板膜流动性与对照组无差异，由于血小板的脂质环境可能会改变其膜流动性，我们接下来研究了血浆甘油三酯对血小板膜流动性的影响。我们将人血小板与高浓度甘油三酯乳剂孵育。结果清楚地表明，孵育培养基中甘油三酯的存在增加了血小板膜流动性。为了进一步阐明甘油三酯对血小板膜的作用机制，我们测定了血小板膜中胆固醇的含量。胆固醇是细胞膜流动性的主要决定因素之一，沿着脂肪酸碳链长度。结果表明，当血小板与高浓度甘油三酯孵育时，血小板膜胆固醇降低，如前所述，血小板膜与神经元质膜共享许多受体。某些先天性脂质代谢异常所引起的脂质环境的改变，可改变神经元膜的性质，从而改变神经元的功能，而血小板膜流动性的测定也可为了解神经元膜的功能提供重要信息。少