INTERACTION OF ETHANOL AND MEMBRANE ETHER LIPIDS

这项提案将解决酒精伤害和细胞之间的关系 膜乙醚类脂，主要是血浆原。最初的方法将是 是膜醚脂浓度和组成与 酒精暴露。成分将以总乙醇为单位制作。 暴露剂量和暴露时间。乙醇诱导膜的意义 乙醚脂质修饰最初将通过相关性进行评估 具有身体依赖性和/或耐受性的浓度和成分 乙醇。细胞膜中乙醚类脂替代品的可能性 内容可能代表对酒精侮辱的适应将由以下人员评估 测定纤溶酶原浓度对物理性质的影响 (粘度、相变和相分离) 脂质体，以及从处理后分离的膜组分 动物。膜浆原的功能意义也将是 利用观察到的纤溶酶原 鱼中枢神经系统膜的浓度可以控制 通过环境温度的变化。因此，纤溶酶原浓度可以 在一个完整的生物体中，这种改变与长期接触乙醇无关。 然后，对急性酒精的行为反应可以独立测量。 以前接触过酒精，并分析了血浆蛋白原 专注度和成分。这项调查的第二阶段将 阐述代谢途径中的机制或特定反应 受酒精暴露的影响。综合的相对贡献或 降解到乙醇引起的血浆蛋白原变化将被估计 用(1-14C)十六醇(1-14C)乙酸酯和14C-乙醇胺标记 在乙醇存在或不存在的情况下的血浆蛋白原。三种不同的 化合物还将允许对特定的 合成途径中受抑制或刺激的反应(S) 乙醇。最初的实验将使用神经母细胞瘤进行。 在培养中保持的细胞。如果在这张图中发现了特定的损伤 这些反应将使用大鼠中枢神经系统组织进行评估。

This proposal will address the relationship between ethanol insult and cell membrane ether lipids, primarily plasmalogens. The initial approach will be to correlate membrane ether lipid concentration and composition with ethanol exposure. The composition will be made in terms of total ethanol dose and period of exposure. The significance of ethanol induced membrane ether lipid modification will be assessed initially by correlation of concentration and composition with physical depenence and/or tolerance to ethanol. The possibility that alternatives in cell membrane ether lipid content may represent adaptation to ethanol insult will be evaluated by measuring the effect of plasmalogen concentration on physical properties (viscosity, phase transition and phase separation) of multilamellar liposomes, as well as well membrane fractions isolated from treated animals. The functional significance of membrane plasmalogens will also be evaluated by taking advantage of the observation that plasmalogen concentrations of fish central nervous system membranes can be manipulated by change in environment temperature. Thus, plasmalogen concentration can be altered independent of chronic ethanol exposure in an intact organism. The behavioral response to acute ethanol can then be measured independent of prior ethanol exposure and analyzed in regard to plasmalogen concentration and composition. The second phase of this investigation will address the mechanism or specific reaction in the metabolic pathway influenced by ethanol exposure. Relative contribution of synthesis or degradation to ethanol elicited changes in plasmalogen will be estimated using (1-14C) hexadecanol (1-14C) acetate and 14C-ethanolamine to label plasmalogen in the presence or absence of ethanol. The three different compounds would also allow prediction to be made concerning specific reaction(s) in the synthetic pathway which are inhibited or stimulated by ethanol. The initial experiments will be carried out using neuroblastoma cells maintained in culture. If specific lesions are identified in this system the reactions will be appraised using rat CNS tissue.