ROLE OF MEMBRANE LIPIDS IN HEAT INJURY

有证据表明，膜结构是（或影响）的目标 高温损伤来自于实验表明膜脂 调节细胞对高温暴露的敏感性。 的方式 然而，膜组分相互作用以影响热损伤， 需要明确的解释 本提案的长期目标是 阐明膜脂在热诱导损伤中的作用， 细胞死亡和病毒灭活，并确定 其中高温损伤和耐热性的发展是 通过对（i）脂质代谢（ii）膜脂质的影响介导， 包括特定膜蛋白微环境的变化， (iii)特异性膜靶点（例如蛋白质）。 我们打算做到这一点 长期目标，通过确定如何灵敏度，耐热性， 脂质代谢、病毒附着和进入（即蛋白质及其脂质 微环境）在细胞中受到影响， 膜组成 这几个参数的范围 将检查与加热细胞和病毒相关的问题。 进一步建立 脂质代谢和细胞热敏感性的变化程度 发生在病毒感染的细胞中，并评估 在病毒生命的各个阶段，病毒包膜的脂质成分 循环（附着、进入以及组装、出芽和释放）。 我们 进一步的目标是看看操纵宿主细胞脂质是否可以改变 病毒脂质、病毒对热的敏感性或病毒的某些方面 生命周期以及病毒脂质或病毒 对热灭活的敏感性被病毒组装所抑制， 耐热宿主细胞 我们的研究发现， 热疗、细胞膜和病毒生命周期 转化为体内动物模型的背景。 除了 他们的重要性，热疗，拟议的研究有更广泛的 影响，与细胞脂质组织的问题有关 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 使用高温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.