REYE'S SYNDROME AND MITOCHONDRIAL ENERGY METABOLISM

雷氏综合症和线粒体能量代谢

• 批准号: 3314387
• 负责人: CHUAN-PU LEE
• 金额: $ 11.19万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-01-01 至 1988-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3314387
• 关键词: Reye's syndrome; bioenergetics; biophysics; calcium; disease /disorder model; electron microscopy; heart cell; human subject; liver cells; membrane permeability; mitochondria; molecular pathology; pathologic process; striated muscles; Reye's syndrome; bioenergetics; biophysics; calcium; disease /disorder model; electron microscopy; heart cell; human subject; liver cells; membrane permeability; mitochondria; molecular pathology; pathologic process; striated muscles

The ultimate goal of this proposed research is to elucidate the mechanism of the pathogenesis of Reye's syndrome (RS). The central theme of our research is to gain deeper insight into the site(s) of regulation, at the molecular level, of mitochondrial disorders in Reye's syndrome. We propose to employ both the in vitro and in vivo approaches to further characterize the action of RS-plasma on mitochondrial structure and function, with allantoin plus calcium ion as the key components responsible for the mitochondrial injuries being our working hypothesis. We plan to use the following approaches: (I). To elucidate the action of RS-plasma, on mitochondrial metabolism by continued investigation of: a. the effects fo RS-plasma, allantoin plus and minus calcium ion on mitochondrial functions in isolated mitochondrial preparations from liver, skeletal muscle and heart; b. the possible origin of allantoin and its content in RS-plasma. (II). To further characterize the action of RS-plasma and allantoin plus and minus calcium ion on membrane permeability of isolated hepatocytes and mitochondrial preparations. (III). To identify the site(s) of structural alterations induced by various treatments in RS-patients and animal model, in isolated hepatocytes and mitochondrial preparations by means of ultrastructural examination in parallel with the biochemical studies. (IV). To develop an animal model in which to test the effects of allantoin plus and minus calcium ion in an in vivo system. Correlation of the clinical parameters together with the biochemical and ultrastructural studies will be made. Knowledge derived from these studies will contribute to our understanding of the pathogenesis of Reye's syndrome at the molecular level and will, in turn, lead to the development of improved therapeutic procedures.

这项拟议研究的最终目标是阐明机制 雷耶综合征（RS）的发病机理。 我们的中心主题 研究是为了更深入地了解监管的地点， Reye综合征线粒体疾病的分子水平。 我们建议 采用体外和体内方法进一步表征 RS-plasma对线粒体结构和功能的作用，并具有 Allantoin Plus钙离子作为负责的关键组成部分 线粒体伤害是我们的工作假设。 我们计划使用 以下方法：（i）。 为了阐明RS-plasma的作用， 线粒体代谢继续进行： 效果fo 线粒体功能上的RS-plasma，Allantoin Plus和负钙离子 在肝脏，骨骼肌和孤立的线粒体制剂中 心; b。 Allantoin的可能起源及其含量在Rs-plasma中。 （ii）。 为了进一步表征RS-Plasma和Allantoin Plus的作用 以及分离的肝细胞膜通透性上的负钙离子和 线粒体制剂。 （iii）。 识别结构的位置 在RS患者和动物模型中各种治疗引起的改变， 在孤立的肝细胞和线粒体制备中 超微结构检查与生化研究并行。 （iv）。 开发一种动物模型，以测试艾兰托因的影响 在体内系统中加上和负钙离子。 相关性 临床参数以及生化和超微结构 将进行研究。 这些研究得出的知识将有助于 为了理解Reye综合征的发病机理 分子水平并将导致改善的发展 治疗程序。