GENETOXIC RESPONSE TO OXIDATIVE DAMAGE

对氧化损伤的遗传毒性反应

• 批准号: 3802308
• 负责人: N J HOLBROOK
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3802308
• 关键词: aging; catalase; fibroblasts; gene induction /repression; hyperoxia; injury /disease stressor; lung; oxidation; oxygenases; physiologic stressor; stress; superoxide dismutase; tissue /cell culture; vascular endothelium

Oxidative stress, resulting from the exposure of cells to "active oxygen" species (AO), is a major cause of both acute and chronic cell injury. Intracellular targets of AO include proteins, lipids, and DNA. Damage to these cellular constituents represents a systemic challenge to the organism perhaps even underlying itself. In bacteria, many genes involving three distinct regulons, oxyR, soxR, and recA, have been shown to be induced in response to oxidative stress. Comparatively little is known about the genetic response to oxidative damage in higher organisms. In this project we have initiated studies to examine the acute genetic response to oxidant damage in the whole lung and in cultured lung fibroblast and endothelial cells exposed to hyperoxic conditions. So far we have shown that several genes are induced in lung fibroblasts within 24 hours of exposure of cells to 95% hyperoxia. These include the known antioxidants catalase and superoxide dismutase, which are induced 3-5 fold, and two additional genes, gadd153 and heme oxygenase, which are induced 20-40 fold above the basal levels. It is likely that the protein products of these genes are part of the protective or repartive response to oxidant injury.

氧化应激，由细胞暴露于“活性氧”引起 物种（AO）是急性和慢性细胞损伤的主要原因。 AO的细胞内靶标包括蛋白质、脂质和DNA。 损坏 这些细胞成分代表了对生物体的系统性挑战 甚至可能隐藏在自身之中。 在细菌中，许多基因涉及三个 不同的调节子，oxyR，soxR和recA，已被证明是诱导的， 氧化应激反应。 相对而言， 高等生物对氧化损伤的遗传反应。 在这个项目中 我们已经开始了研究， 全肺和培养的肺成纤维细胞和内皮细胞损伤 暴露于高氧条件下的细胞。 到目前为止，我们已经证明， 在细胞暴露24小时内， 到95%的高氧。 这些包括已知的抗氧化剂过氧化氢酶和 超氧化物歧化酶，其被诱导3-5倍，和两个另外的基因， GADD 153和血红素加氧酶，其被诱导为基础水平的20-40倍。 程度. 这些基因的蛋白质产物很可能是 对氧化损伤的保护或修复反应。