Effect of aging and neurodegenerative disorders on cellular membrane fluidity

细胞膜的生理特性通过调节细胞的运动性、与底物的粘附性以及受体与配体的亲和力，决定了许多重要的细胞功能。膜流动性是细胞膜的生理特性之一，已经得到了广泛的研究。我们测量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，可以作为一个很好的模型来探测神经元功能的变化。我们利用脂膜探针的稳态各向异性来监测膜流动性的变化。使用该探针，我们测量了阿尔茨海默病和雷特综合征患者血小板膜流动性。结果发现，阿尔茨海默病患者的血小板膜流动性高于年龄匹配的对照组。最近，人们发现apop…阿尔茨海默病患者中更多的Rotein E是异常的。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正常对照组无明显差异，由于血小板膜脂环境可能改变其膜流动性，因此我们接下来研究血浆甘油三酯对血小板膜流动性的影响。我们用高浓度的甘油三酯乳剂孵育人的血小板。结果表明，孵育液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上胆固醇的含量。胆固醇是细胞膜流动性和脂肪酸碳链长度的主要决定因素之一。研究表明，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有许多共同的受体。在某些先天性脂代谢异常中，脂质环境的改变可能会改变神经细胞膜的性质，从而改变神经元的功能。因此，测定血小板膜流动性也可以为我们提供有关神经细胞膜功能的重要信息。较少

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