TOXIC METABOLITES OF OXYGEN IN CATARACTOGENESIS

白内障发生中氧的有毒代谢物

• 批准号: 3257327
• 负责人: KAILASH C BHUYAN
• 金额: $ 21.75万
• 依托单位: MOUNT SINAI SCHOOL OF MEDICINE OF CUNY
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-09-01 至 1986-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3257327
• 关键词: Schiff bases; aging; aminoacid transport; antioxidants; ascorbate; catalase; cataract; chromatography; electron spin resonance spectroscopy; fluorescence spectrometry; free radicals; gas chromatography; glutathione peroxidase; human tissue; hydrogen peroxide; lens proteins; membrane lipids; molecular pathology; respiratory oxygen; selenium; superoxide dismutase; tissue /cell culture

As stated in the earlier report, our overall objective is to investigate molecular mechanisms of cataractogenesis and to search for medical therapy which may prevent or arrest cataract at an early stage. Our studies on cataract induced by 3-amino-1H-1,2,4-triazole, human senile cataract, and selenium-induced cataract strongly suggest that toxic oxygen metabolites, such a O2, H2O2, OH and/or 1O2 are triggering agents in cataractogenesis. The enzymatic defenses provided by catalase, superoxide dismutase (SOD), and GSH peroxidase of lens and other eye tissue against the toxic derivatives of oxygen are of utmost importance in protecting the crystalline lens from oxidative damage. As seen from our recent experimental work, H2O2 of aqueous humor was significantly increased and the activities of lenticular catalase and SOD were decreased in selenium-induced cataract in rat, showing the involvement of similar biochemical mechanism. A fall in the protein-SH of lens showed oxidation of protein and a rise in lenticular malondialdehyde (MDA) evidenced peroxidation of membrane lipids. Cataract induced by selenium may arise from conformational changes in functional and structural proteins of lens due to the formation of disulfide and selenotrisulfide crosslinks by reaction of SH-groups with selenite. We propose to explore these reactions. It is one of our objectives to investigate the possibility of the involvement of similar biochemical mechanism in various experimental cataracts induced by UV, X-ray, naphthalene etc. Further experimental work will be conducted to study the products formed by reaction between MDA and lenticular proteins and amino acids in relation to crosslinking and aggregation. Functional integrity of lens plasma membrane in cataract will be assessed by studying cation transport and amino acid transport. Biosynthesis of protein in cataract will be examined by estimating the incorporation of 14C-L-leucine into lenticular protein. We will also continue the attempts to prevent or arrest cataract in animal model by using antioxidants.

正如早些时候的报告所述，我们的总体目标是调查 白内障发生的分子机制及其药物治疗 可以在早期阶段预防或阻止白内障。我们对白内障的研究 3-氨基-1H-1，2，4-三氮唑诱导的人老年性白内障 硒诱导的白内障强烈提示有毒的氧代谢物，如 O2、H_2O_2、OH和/或O_2是白内障发生的触发因素。这个 过氧化氢酶、超氧化物歧化酶和谷胱甘肽提供的酶防御 晶状体和其他眼组织的过氧化物酶对氧的毒性衍生物的保护作用 对于保护水晶晶状体免受氧化至关重要 损坏。 从我们最近的实验工作可以看出，房水中的过氧化氢是 豆状体内过氧化氢酶和超氧化物歧化酶活性显著升高。 减少硒诱导的大鼠白内障，显示其参与了 类似的生化机制。晶状体蛋白-SH的下降显示 蛋白质氧化和晶状体丙二醛(MDA)升高 膜脂过氧化。硒引起的白内障可能是由 晶状体功能和结构蛋白的构象变化 SH基反应生成二硫化物和三硫代硒的交联物 加了亚硒酸盐。我们建议探讨这些反应。它是我们的一家 目的探讨同种病毒感染的可能性。 紫外线、X射线、辐射诱发多种实验性白内障的生化机制 将进行进一步的实验工作，以研究 丙二醛与豆状蛋白质和氨基酸反应生成的产物 与交联性和聚集性有关。晶状体的功能完整性 白内障的质膜将通过研究阳离子转运和 氨基酸运输。白内障中蛋白质的生物合成将通过 ~(14)C-L-亮氨酸掺入豆状蛋白的估算。我们会 还继续尝试通过以下方法预防或阻止动物模型的白内障 使用抗氧化剂。