ALCOHOL-MEMBRANE INTERACTION IN THE BRAIN: AGING EFFECT

大脑中的酒精与膜的相互作用：衰老效应

• 批准号: 3108780
• 负责人: ALBERT Y SUN
• 金额: $ 14.02万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-07-01 至 1992-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3108780
• 关键词: acylation; acyltransferase; aging; alcoholic beverage consumption; alcoholism /alcohol abuse; animal age group; brain cell; brain metabolism; cell membrane; density gradient ultracentrifugation; dietary supplements; drug tolerance; drug withdrawal; enzyme mechanism; ethanol; fluorescence spectrometry; gel electrophoresis; laboratory mouse; membrane lipids; membrane permeability; membrane structure; nutrition related tag; pathogenic diet; peroxidation; radionuclides; scintillation counter; spectrometry; synaptosomes; thin layer chromatography; tissue /cell culture

There is increasing experimental evidence to support the concept of free radical damage to cellular constituents. In general, an increase in free radical generation would lead to alterations of biochemical and biophysical properties of cells. The process of free radical generation may also be important in the pathological manifestations of aging and alcoholism. The overall objective of this project is to investigate the involvement of free radicals in brain membrane deterioration, and to examine whether alcohol- enhanced free radical formation will affect the aging process. Specifically, experiments will be designed to (1) test the hypothesis that free radicals play and important role in the aging process, and that ethanol accelerates aging process through potentiation or enhancement of the lipid peroxidation process; (2) evaluate specific membrane-dependent processes with respect to aging and chronic ethanol administration; (3) study the body protective system in brain against the toxic effects of free radical attack and (4) evaluate the importance of dietary antioxidants, such as vitamins E and C, in providing protection against the peroxidative damage resulted from alcohol ingestion. For experiments described in this project, we will continue to use C57BL/6NNIA mice as the animal model. The spin trapping technique will be employed to detect free radical formation in both in vitro and in vivo systems. In addition, the activity of enzymes involved in metabolism of the peroxidation process in brain, such as supreoxide dismutase, catalase, and glutathione peroxidase will also be investigated. Since many neuronal membrane processes are known to depend on the microenvironment of membrane lipids for proper functioning, we will specifically examine the effects of age and alcohol and (Na+, K+)-ATPase activity, enzyme its kinetics, phosphorylated intermediates and ouabain binding properties in mouse synaptic plasma membranes. In addition, other membrane-bound enzymes which are important in modulating membrane lipids will be examined and tested for their sensitivity to the radical formation. It is anticipated that through this systematic investigation, new information may be obtained regarding the mechanism of membrane deterioration due to age and/or alcohol intake, and the effectiveness of dietary supplement of vitamin E and vitamin C on alleviating some of the changes due to aging and/or alcohol abuse.

越来越多的实验证据支持这一概念 自由基对细胞成分的损害。 一般来说， 自由基生成的增加会导致 细胞的生物化学和生物物理特性。 的过程 自由基的产生也可能是重要的病理 衰老和酗酒的表现。 的总体目标 这个项目是调查自由基参与 脑细胞膜退化，并检查是否酒精- 增强的自由基形成将影响老化过程。 具体而言，实验将被设计为（1）测试 自由基在衰老中作用假说 乙醇加速老化过程， 增强或加强脂质过氧化过程;（2） 评估特定的膜依赖性过程， 衰老和慢性乙醇给药;（3）研究身体 大脑中的保护系统对抗自由基的毒性作用 （4）评估饮食的重要性 抗氧化剂，如维生素E和C，提供保护 防止酒精摄入引起的过氧化损伤。 对于本项目中描述的实验，我们将继续使用 C57 BL/6 NNIA小鼠作为动物模型。 自旋捕获技术 将被用来检测自由基的形成，在体外 和体内系统。 此外，参与酶的活性 在大脑过氧化过程的代谢中， 超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶将 也要加以研究。 由于许多神经元膜过程 已知依赖于膜脂质的微环境， 正常运作，我们将专门研究年龄的影响， 乙醇和（Na+，K+）-ATP酶活性，酶动力学， 磷酸化中间体和哇巴因结合特性 小鼠突触质膜。 此外，其他膜结合 在调节膜脂质中重要的酶将被 检查并测试了它们对自由基形成的敏感性。 预计通过这次系统的调查， 可以获得关于膜的机制的信息， 由于年龄和/或酒精摄入而恶化， 膳食补充维生素E和维生素C对 减轻由于衰老和/或酒精滥用引起的一些变化。