RELATIONSHIP OF CELLULAR REDOX STATE AND THERMOTOLERANCE

细胞氧化还原态与耐热性的关系

• 批准号: 3963241
• 负责人: A RUSSO
• 金额: --
• 依托单位: DIVISION OF CANCER TREATMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3963241
• 关键词: cell death; electrolyte balance; environmental stressor; glutathione; human therapy evaluation; intracellular; membrane structure; neoplasm /cancer thermotherapy; oxidation reduction reaction; polyamines; thermostability; thiols

Hyperthermia is currently being evaluated as a potential cancer treatment modality. The mechanism(s) of hyperthermia killing and the induction of thermal resistance (thermotolerance) are not known. We will examine the role of the cellular reduction potential during and after heating to determine its role or alteration during thermal stress. This will be accomplished by using drugs which either bind GSH or prevent its synthesis. There appears to be a relationship between the synthesis of heat shock proteins and the induction of heat resistance. The effect of thiol modulation will be studied in the context of heat shock proteins. Recently, several compounds have been introduced which elevate cellular GSH. These compounds will be synthesized and evaluated in regard to thermal response. Continued effort to inter-relate oxidative stress and the biochemical induction of genetic materials center around GSH metabolism. There is also interest in the role that GSH has on maintaining the integrity of the membrane. Heat sensitizers, such as polyamines will be studied to determine their impact on the cellular redox systems as reflected by GSH levels.

热疗目前正在被评估为一种潜在的癌症治疗方法。 情态。高温致死的机制(S)及其诱导 热阻(耐热性)是未知的。我们将研究 细胞还原电位在加热过程中和加热后的作用 确定其在热应激期间的作用或变化。这将是 通过使用药物来结合GSH或阻止其 综合。似乎有关系的合成之间的关系 热休克蛋白与耐热性的诱导。的影响 硫醇的调节将在热休克蛋白的背景下进行研究。 最近，已经有几种化合物被引入，它们可以提高细胞 谷胱甘肽。这些化合物将被合成并在以下方面进行评估 热反应。继续努力将氧化应激和 遗传物质的生化诱导以谷胱甘肽为中心 新陈代谢。还有人感兴趣的是谷胱甘肽在维持 膜的完整性。热敏剂，如多胺将 被研究以确定它们对细胞氧化还原系统的影响 反映在GSH水平上。