ALCOHOL ACTION ON MEMBRANE STRUCTURES

酒精对膜结构的作用

• 批准号: 6563154
• 负责人: Theodore F Taraschi
• 金额: $ 13.07万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-12-01 至 2002-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6563154
• 关键词: biological signal transduction; biophysics; chemical models; electron spin resonance spectroscopy; ethanol; fluidity; laboratory rat; lipid bilayer membrane; lipid structure; liposomes; membrane activity; membrane fusion; membrane lipids; membrane model; membrane structure; microsomes; mitochondrial membrane; nuclear magnetic resonance spectroscopy; phosphatidylinositols; phospholipids; physical chemical interaction; protein binding; synaptosomes

The long term goal of this project is to characterize the interaction of ethanol with cellular membranes. Ethanol modifies the properties of the cell membranes of all the major body organs and many of the actions of ethanol are manifest at the level of the cell membrane. The manner by which ethanol, both acutely and chronically, alters the ability of cellular membranes to accommodate and bind exogenous substances such as peptides, proteins and phospholipids will be investigated. The acute and chronic effects of ethanol on the binding properties of rat liver microsomes, mitochondria, brain synaptosomes and their lipid extracts will be characterized. The dependence of lipophile binding on membrane fluidity, curvature stress, and composition will be assessed using nuclear magnetic resonance and electron paramagnetic resonance. It will be established whether the adaptive response to chronic ethanol exposure is an adaptation to chronic membrane fluidization or chronic curvature stress. The acute and chronic effects of ethanol on membrane domain structure in rat liver microsomes and brain synaptosomes, their lipid extracts, and membrane models for the cytoplasmic leaflet of the plasma membrane thought to be involved in the regulation of polyphosphoinositide signaling will be established. The physical and biochemical determinants of domain structure will be assessed using magnetic resonance methods and radiolabel binding methods. The effects of acute and chronic ethanol exposure upon phospholipid (phosphatidylinositol) transfer mediated by the phosphatidylinositol transfer protein will be investigated. Interference with the binding, transfer and incorporation of newly synthesized phosphatidylinositol into inositol lipid signaling pathways in the plasma membrane by acute or chronic ethanol exposure is likely to alter phosphatidylinositol 4,5-bisphosphate dependent processes. The relationship between domain formation and the effects of ethanol on phosphatidylinositol transfer activity will be investigated.

该项目的长期目标是描述 乙醇与细胞膜。乙醇改变了 所有主要身体器官的细胞膜以及 乙醇在细胞膜水平上是明显的。以何种方式 乙醇，无论是急性还是慢性， 细胞膜以容纳和结合外源物质， 将研究肽、蛋白质和磷脂。急性和 乙醇对大鼠肝脏结合特性的慢性影响 微粒体、线粒体、脑突触体及其脂质提取物将 被描述。亲脂分子结合的膜依赖性 流动性、弯曲应力和组成将使用核分析仪进行评估。 磁共振和电子顺磁共振。将 确定了对慢性乙醇暴露的适应性反应是否 对慢性膜流体化或慢性弯曲的适应 应力乙醇对膜结构域的急性和慢性影响 大鼠肝微粒体和脑突触体结构、脂质 提取物和血浆细胞质小叶的膜模型 被认为参与调节多磷酸肌醇的膜 将建立信令。物理和生物化学决定因素 将使用磁共振方法评估畴结构， 放射性标记结合方法。急性和慢性乙醇的影响 暴露于磷脂（磷脂酰肌醇）转移介导的 将研究磷脂酰肌醇转移蛋白。 干扰 与新合成的 磷脂酰肌醇转化为肌醇脂质信号通路在血浆中 急性或慢性乙醇暴露可能会改变膜 磷脂酰肌醇4，5-二磷酸依赖性过程。的 微区形成与乙醇作用的关系 将研究磷脂酰肌醇转移活性。