ROLE OF MEMBRANE LIPIDS IN HEAT INJURY

膜结构是(或影响)目标的证据 高热损伤来自于实验表明，膜脂 调节细胞对高温暴露的敏感性。以一种方式 然而，膜组件相互作用会影响热损伤 需要明显的澄清。这项提议的长期目标是 阐明膜脂在热损伤中的作用 细胞死亡和病毒灭活，并确定 高热损伤与耐热性的发展 通过影响(I)脂代谢(Ii)膜脂， 包括特定膜蛋白微环境的变化和 (3)特定的膜靶标(例如蛋白质)。我们打算实现这一目标 长期目标是通过确定敏感度、耐热性、 脂代谢、病毒附着和进入(即蛋白质及其脂质 微环境)在已适应其脂质的细胞中受到影响 膜成分。这几个参数的大小 相关的加热细胞和病毒将被检查。进一步确立 脂代谢和细胞热敏感性的变化程度 并评估病毒感染细胞中病毒的重要性 病毒生命不同阶段病毒包膜的脂类成分 循环(附着、进入以及组装、萌芽和释放)。我们 进一步的目的是看看操纵宿主细胞的脂质是否可以改变 要么是病毒脂类，要么是病毒对热的敏感性，要么是病毒的某些方面 生命周期以及病毒脂类或病毒的变化 对热灭活的敏感性是由病毒组装引起的 耐热宿主细胞。我们对两者之间相互关系的发现 体温过高、细胞膜和病毒生命周期 翻译成活体动物模型的背景。除了……之外 它们对体温过高的重要性，拟议的研究范围更广 暗示，与细胞脂质组织的问题相关 和病毒生物学。预计我们的研究将提供基本的 将回答与临床设计相关的问题的信息 使用热疗治疗癌症和病毒性疾病的方案。

Evidence that membrane structures are (or effect) the targets of hyperthermic damage comes from experiments showing that membrane lipids modulate sensitivity of cells to hyperthermic exposure. The way in which membrane components interact to influence heat damage, however, still requires appreciable clarification. The long term goal of this proposal is to clarify the role played by membrane lipids in heat-induced injury and death of cells and inactivation of viruses and to establish the extent to which hyperthermic damage and the development of thermal tolerance are mediated through effects on (i) lipid metabolism (ii) membrane lipids, including changes in the microenvironment of specific membrane proteins and (iii) specific membrane targets (e.g. proteins). We intend to achieve this long term objective by determining how sensitivity, thermal tolerance, lipid metabolism, viral attachment and entry (i.e. proteins and their lipid microenvironments) are affected in cells which have adapted their lipid membrane composition. The extent to which these several parameters are related in heated cells and viruses will be examined. Further to establish the extent of changes in lipid metabolism and cellular heat sensitivity that occur in virally infected cells and evaluate the importance of the lipid component of the viral envelope in various phases of the virus life cycle (attachment, entry and also assembly, budding and release). We further aim to see whether manipulating the host cell lipid can modify either viral lipids, viral sensitivities to heat or aspects of the viral life cycle and whether changes in either viral lipids or viral sensitivities to heat inactivation are occasioned by viral assembly in thermotolerant host cells. Our findings on the interrelationships between hyperthermia, cellular membranes and the viral life cycle will be translated into the context of an in vivo animal model. In addition to their importance for hyperthermia, the proposed studies have wider implications, being relevant to questions of cellular lipid organization and viral biology. It is anticipated that our studies will provide basic information that will answer questions relevant to the design of clinical protocols using hyperthermia to treat cancer and viral diseases.