Storz G, Tartaglia L A
Department of Molecular Biology, Massachusetts General Hospital, Boston 02114.
J Nutr. 1992 Mar;122(3 Suppl):627-30. doi: 10.1093/jn/122.suppl_3.627.
The study of the bacterial response to hydrogen peroxide has given general insights into how cells defend against deleterious oxidants. Treatment of Salmonella typhimurium and Escherichia coli cells with low doses of hydrogen peroxide results in the induction of 30 proteins and resistance to killing by higher doses of hydrogen peroxide. The expression of nine of the hydrogen peroxide-inducible proteins, including the antioxidant enzymes catalase, glutathione reductase and an alkyl hydroperoxide reductase, is controlled by the positive regulator oxyR. Strains carrying deletions of the oxyR gene are hypersensitive to hydrogen peroxide and have increased levels of spontaneous mutagenesis during aerobic growth. The OxyR protein is homologous to the LysR-NodD family of bacterial regulatory proteins and binds to the promoters of oxyR-regulated genes. The oxidized, but not the reduced, form of the OxyR protein activates transcription of oxyR-regulated genes in vitro, suggesting that direct oxidation of the OxyR protein brings about a conformation change by which OxyR senses an oxidative stress signal and then activates the expression of defense activities.
对细菌对过氧化氢反应的研究使人们对细胞如何抵御有害氧化剂有了总体认识。用低剂量过氧化氢处理鼠伤寒沙门氏菌和大肠杆菌细胞会诱导30种蛋白质的产生,并使其对高剂量过氧化氢的杀伤产生抗性。包括抗氧化酶过氧化氢酶、谷胱甘肽还原酶和烷基过氧化氢还原酶在内的9种过氧化氢诱导蛋白的表达受正调控因子oxyR控制。携带oxyR基因缺失的菌株对过氧化氢高度敏感,且在有氧生长过程中自发突变水平增加。OxyR蛋白与细菌调节蛋白的LysR-NodD家族同源,并与oxyR调节基因的启动子结合。OxyR蛋白的氧化形式而非还原形式在体外激活oxyR调节基因的转录,这表明OxyR蛋白的直接氧化会引起构象变化,通过这种变化OxyR感知氧化应激信号,进而激活防御活性的表达。