OxyR and SoxRS regulation of fur
OxyR and SoxRS regulation of fur
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DOI：
10.1128/jb.181.15.4639-4643.1999
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发表时间：
1999-08-01
影响因子：
3.2
通讯作者：
Storz, G
中科院分区：
文献类型：
--
作者：
Zheng, M;Doan, B;Storz, G
活性氧的细胞毒性作用主要由铁介导。过氧化氢与铁反应，通过芬顿反应形成极具活性和破坏性的羟基自由基。超氧阴离子加速该反应，因为超氧化物歧化导致过氧化氢水平增加，并且因为超氧化物通过攻击铁-硫蛋白来提高细胞内铁浓度。我们发现，调节大肠杆菌对氧化应激的反应，OxyR和SoxRS，激活Fur的表达，Fur是铁离子摄取的全局抑制因子。野生型菌株中的过氧化氢诱导了编码毛皮的转录物，但在Delta oxyR菌株中没有，DNA酶I足迹分析表明OxyR与毛皮启动子结合。在用产生超氧化物的化合物百草枯处理的细胞中，我们观察到一个较长的转录本的诱导，包括毛皮及其直接上游基因fldA，它编码一个黄素氧还蛋白。这种多顺反子mRNA在野生型菌株中由百草枯诱导，但在Delta soxRS菌株中不诱导，并且显示SoxS与fldA启动子结合。这些结果表明，铁代谢与氧化应激防御协调调节。
The cytotoxic effects of reactive oxygen species are largely mediated by iron. Hydrogen peroxide reacts with iron to form the extremely reactive and damaging hydroxyl radical via the Fenton reaction. Superoxide anion accelerates this reaction because the dismutation of superoxide leads to increased levels of hydrogen peroxide and because superoxide elevates the intracellular concentration of iron by attacking iron-sulfur proteins. We found that regulators of the Escherichia coli responses to oxidative stress, OxyR and SoxRS, activate the expression of Fur, the global repressor of ferric ion uptake. A transcript encoding Fur was induced by hydrogen peroxide in a wild-type strain but not in a Delta oxyR strain, and DNase I footprinting assays showed that OxyR binds to the fur promoter. In cells treated with the superoxide-generating compound paraquat, we observed the induction of a longer transcript encompassing both fur and its immediate upstream gene fldA, which encodes a flavodoxin. This polycistronic mRNA is induced by paraquat in a wild-type strain but not in a Delta soxRS strain, and SoxS was shown to bind to the fldA promoter. These results demonstrate that iron metabolism is coordinately regulated with the oxidative stress defenses.