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: 3108784
• 负责人: ALBERT Y SUN
• 金额: $ 13.47万
• 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/3108784
• 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。一般而言，一个 自由基生成的增加会导致 细胞的生化和生物物理性质。这一过程 自由基的产生也可能在病理过程中起重要作用。 衰老和酗酒的表现。总的目标是 本项目旨在研究自由基在人体内的作用。 脑膜退化，并检查酒精是否- 增强的自由基形成会影响衰老过程。 具体地说，实验将被设计为(1)测试 自由基在衰老中起重要作用的假说 乙醇通过以下途径加速老化过程 加强或加强脂质过氧化过程；(2) 根据以下方面评估特定的膜依赖过程 衰老和慢性酒精摄入；(3)研究身体 大脑中的保护系统对抗游离的毒性效应 激进攻击和(4)评估饮食的重要性 抗氧化剂，如维生素E和C，在提供保护方面 防止酒精摄入造成的过氧化损伤。 对于本项目中描述的实验，我们将继续使用 以C57BL/6NNIA小鼠为动物模型。自旋捕获技术 将被用来检测这两种物质在体外的自由基形成 和活体系统。此外，所涉及的酶的活性 在大脑过氧化过程的新陈代谢中，例如 超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶 也被调查。由于许多神经元膜突起是 已知取决于膜脂的微环境 正常的功能，我们将具体检查年龄的影响 酒精和(Na+，K+)-ATPase活性，酶及其动力学， 磷酸化中间体和哇巴因结合特性 小鼠突触质膜。此外，其他膜结合在一起 对调节膜脂很重要的酶将是 检查并测试它们对自由基形成的敏感性。 预计通过此次系统调研，新的 可以获得关于膜的机制的信息 因年龄和/或饮酒而恶化，以及 膳食补充维生素E和维生素C对人体健康的影响 减轻因衰老和/或酗酒而产生的一些变化。