ROLE OF IRON IN TOXICITIES AND PATHOLOGIES

铁在毒性和病理学中的作用

• 批准号: 3253295
• 负责人: STEVEN D. AUST
• 金额: $ 9.27万
• 依托单位: UTAH STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-05-01 至 1992-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3253295
• 关键词: alloxan; carbon tetrachloride; catalyst; chelating agents; chromatography; doxorubicin; enzyme mechanism; ferritin; ferroxidase; gel electrophoresis; iron; laboratory rat; oxidation; paraquat; protein purification; radiation sensitivity; toxicology

We propose that iron catalyzes the free radical oxidation of biomolecules that results in the toxicity of redox cycling chemicals, irradiation damage and iron overload. The iron that catalyzes these toxicities or pathologies must be a low molecular weight chelate of iron which normally exists in very low concentration or otherwise does not catalyze the oxidation of tissue macromolecules. Upon iron overload or the exposure to chemicals or conditions which promote the release of iron from ferritin, the released iron has the potential to be toxic. We hypothesize that this toxicity may be at least minimized by ceruloplasmin catalyzed oxidation and sequestration of the iron in ferritin. The long-term objective of the proposed research is to study ferritin and ceruloplasmin with regards to their ability to sequester iron in order to devise an effective therapeutic system. We propose to determine if a number of redox cycling chemicals or irradiation cause the release of iron from ferritin in vivo in a number of tissues, and to determine if ceruloplasmin and ferritin might provide protection against the toxicity of this iron. We propose to study paraquat, diquat, carbon tetrachloride, adriamycin, alloxan and Y-irradiation in their respective target tissues. We propose to study the interactions between ceruloplasmin and serum ferritin, three isoferritins, and the recently described lipid-associated ferritin.

我们认为铁催化自由基氧化。 导致氧化还原循环毒性的生物分子 化学物质、辐射损伤和铁超载。这把熨斗 催化这些毒性或致病作用必须是低分子的 通常存在于极低浓度的铁的重量络合物 浓度或其他条件不会催化氧化 组织大分子。在铁超载或暴露于 促进铁的释放的化学物质或条件 铁蛋白，释放出来的铁具有潜在的毒性。我们 假设这种毒性至少可以通过以下方式最小化 铜蓝蛋白催化铁的氧化和截留 铁蛋白。拟议研究的长期目标是 研究铁蛋白和铜蓝蛋白的能力 隔离铁以便设计出有效的治疗系统。 我们建议确定一些氧化还原循环化学品或 照射引起体内铁蛋白中铁的释放 组织数量，并确定铜蓝蛋白和铁蛋白 可能对这种铁的毒性起到保护作用。我们 建议研究百草枯、敌草枯、四氯化碳、 阿霉素、四氧嘧啶和Y-射线在各自靶点的应用 纸巾。我们建议研究它们之间的相互作用 铜蓝蛋白和血清铁蛋白，三种异铁蛋白，以及 最近发现了脂质相关铁蛋白。