ANTIOXIDANT ENZYMES AND AGING IN TRANSGENIC DROSOPHILA

转基因果蝇的抗氧化酶和衰老

• 批准号: 2050217
• 负责人: RAJINDAR S SOHAL
• 金额: $ 20.26万
• 依托单位: SOUTHERN METHODIST UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-07-01 至 1997-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2050217
• 关键词: DNA damage; Drosophilidae; aging; animal mortality; antioxidants; cell transformation; enzyme induction /repression; free radical oxygen; gene dosage; genetically modified animals; glucose 6 phosphate dehydrogenase; glutathione reductase; oxidative stress; oxygen consumption; superoxide dismutase

The general goal of the prospective studies is to understand the causes of the aging process in animals. Endogenously-generated oxygen free radicals have been widely postulated to play a causal role in the aging process; however, few studies have been conducted to directly test the validity of this hypothesis. The purpose of the proposed experiments is to directly test the main prediction of this hypothesis: that a decrease in the level of oxidative stress should slow down the aging process. Extra copies of genes that play key roles in the antioxidative system will be introduced into the Drosophila melanogaster genome and the impact of overexpression on age-related biochemical and physiological changes will be assessed. Effects of the overexpression of the Mn superoxide dismutase, glutathione reductase, glutamylcysteine synthetase and glucose-6-phosphate dehydrogenase will be studied; we have previously examined the effects of Cu-Zn superoxide dismutase and catalase. Because the overexpression of single antioxidative genes may create a biochemical imbalance in an inter- related defense mechanism, a major effort will be made to construct transgenic strains with balanced antioxidative defenses. Results of this study should critically test the veracity of the free radical hypothesis of aging by indicating if the major defenses against reactive oxygen species play a causal role in the aging process of Drosophila. Knowledge gained from this study should help in developing strategies for the manipulation of the aging process in mammalian systems.

前瞻性研究的一般目标是了解 动物的衰老过程。内源性产生的氧自由基 已被广泛假定在衰老过程中发挥因果作用； 但是，很少有研究直接测试 这个假设。提出的实验的目的是直接 检验该假设的主要预测：该水平下降 氧化应激应减缓衰老过程。额外的副本 将引入在抗氧化系统中起关键作用的基因 进入果蝇的果蝇基因组和过表达的影响 将评估与年龄有关的生化和生理变化。效果 Mn超氧化物歧化酶的过表达谷胱甘肽 还原酶，谷氨酰胺半胱氨酸合成酶和葡萄糖-6-磷酸盐 将研究脱氢酶；我们以前已经检查了 Cu-Zn超氧化物歧化酶和过氧化氢酶。因为过表达 单一抗氧化基因可能会在间断中造成生化失衡 相关的防御机制，将作出重大努力来构建 具有平衡抗氧化防御的转基因菌株。结果 研究应批判性地检验自由基假设的准确性 通过指示反应性氧的主要防御能力来衰老 在果蝇的衰老过程中起因果作用。知识获得了 从这项研究中应有助于制定操纵策略 哺乳动物系统中的衰老过程。