Trace element dynamics in the vertebrate eye

脊椎动物眼中的微量元素动态

• 批准号: 6635566
• 负责人: MARY C McGahan
• 金额: $ 32.96万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-04-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6635566
• 关键词: animal tissue; antioxidants; biological transport; cataract; dogs; enzyme activity; epithelium; ferritin; fluorescent dye /probe; iron metabolism; lens; lens proteins; organ culture; oxidative stress; pathologic process; radiobiology; statistics /biometry; trace elements; transfection; ultraviolet radiation

DESCRIPTION (provided by applicant): Cataract is a significant health and economic problem worldwide. Oxidative damage has been implicated as a major causative factor in cataract formation. While iron (Fe) catalyzed free radical reactions are responsible for virtually all oxidative tissue damage, little information is available concerning Fe metabolism, storage and utilization in the lens. Storage of Fe in a non-reactive form in ferritin, prevents oxidative damage. Ferritin is made by the lens and a mutation resulting in dysregulation of the synthesis of ferritin subunits results in early bilateral cataracts in humans. The overlying Hypothesis of this proposal is that the uptake of Fe by lens epithelial cells and its movement between a cytoplasmic pool and sites of storage and utilization are carefully controlled under normal physiological conditions. Factors which increase the concentration of Fe in a low molecular weight cytoplasmic pool cause increased susceptibility to oxidative stress and UV irradiation, while a decrease in the size of this pool is protective. The first specific aim of this proposal is to determine how intracellular Fe dynamics, including Fe uptake and efflux, synthesis and concentration of ferritin, storage of Fe in ferritin and the amount of Fe in a low molecular weight cytoplasmic pool are altered by environmental factors and changes in ferritin subunit composition. The second specific aim is to determine whether disturbances in normal Fe distribution within lens epithelial cells result in altered cellular metabolism and affect their ability to withstand oxidative stress or UV irradiation. The results of these studies will provide information essential to our understanding of the metabolism and safe storage of Fe, the central component of damaging oxidative reactions. Such information could lead to the development of effective therapeutic interventions for the delay or prevention of cataract progression.

描述（由申请人提供）：白内障是一种重要的健康和 世界范围内的经济问题。氧化损伤被认为是主要的损伤 白内障形成的致病因素。而铁（Fe）催化自由基 反应几乎是所有氧化组织损伤的原因，但很少 有关铁代谢、储存和利用的信息 镜头。 Fe 以非反应形式储存在铁蛋白中，防止氧化 损害。铁蛋白是由晶状体产生的，突变会导致失调 铁蛋白亚基合成的影响导致早期双侧白内障 人类。 该提案的首要假设是晶状体对铁的吸收 上皮细胞及其在细胞质库和细胞位点之间的运动 在正常生理条件下仔细控制储存和使用 状况。提高低分子铁浓度的因素 细胞质池重量增加对氧化应激的敏感性增加 紫外线照射，同时缩小这个水池的大小是有保护作用的。 该提案的第一个具体目标是确定细胞内 Fe 如何 动力学，包括铁的吸收和流出、合成和浓度 铁蛋白、铁蛋白中铁的储存量以及低分子铁的含量 细胞质库的重量会受到环境因素和细胞质变化的影响 铁蛋白亚基组成。第二个具体目标是确定是否 晶状体上皮细胞内正常铁分布的紊乱导致 改变细胞代谢并影响其抵抗氧化的能力 压力或紫外线照射。 这些研究的结果将为我们提供重要的信息 了解核心成分铁的代谢和安全储存 破坏性氧化反应。这些信息可能会导致发展 延迟或预防白内障的有效治疗干预措施 进展。