GENETOXIC RESPONSE TO OXIDATIVE DAMAGE

点击翻译按钮获取中文摘要

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.