ALCOHOL ACTION ON MEMBRANE STRUCTURES

该项目的长期目标是描述 乙醇与细胞膜。乙醇改变了大豆的性质 所有主要身体器官的细胞膜和许多活动 乙醇存在于细胞膜的水平上。通过以下方式 乙醇，无论是剧烈的还是长期的，都会改变 容纳和结合外源物质的细胞膜，如 将研究多肽、蛋白质和磷脂。急性子和 乙醇对大鼠肝脏结合特性的慢性影响 微生物体、线粒体、脑突触体及其脂类提取物 被刻画出来。亲脂性结合对膜的依赖性 流动性、曲率应力和成分将使用原子核进行评估 磁共振和电子顺磁共振。会是 确定了对慢性酒精暴露的适应性反应是否 对慢性膜流态化或慢性曲率的适应 压力。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的结构及其脂类 萃取物和质叶的膜模型 膜被认为参与多磷肌醇的调节 将建立信令。物理和生化决定因素 将使用磁共振方法和 放射性标记结合方法。急性和慢性酒精对人体的影响 介导磷脂(磷脂酰肌醇)转移的暴露 将对磷脂酰肌醇转移蛋白进行研究。干扰 结合、转移和结合新合成的 磷脂酰肌醇在血浆中进入肌醇脂信号转导通路 急性或慢性乙醇暴露可能会改变细胞膜 磷脂酰肌醇4，5-二磷酸依赖过程。这个 结构域形成与乙醇作用的关系 将对磷脂酰肌醇转移活性进行研究。

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.