LETHAL OXIDATIVE DAMAGE AND MUTAGENESIS ARE GENERATED BY IRON IN DELTA-FUR MUTANTS OF ESCHERICHIA-COLI - PROTECTIVE ROLE OF SUPEROXIDE-DISMUTASE
LETHAL OXIDATIVE DAMAGE AND MUTAGENESIS ARE GENERATED BY IRON IN DELTA-FUR MUTANTS OF ESCHERICHIA-COLI - PROTECTIVE ROLE OF SUPEROXIDE-DISMUTASE
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DOI：
10.1128/jb.177.9.2305-2314.1995
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发表时间：
1995-05-01
影响因子：
3.2
通讯作者：
DESPIED, S
中科院分区：
文献类型：
--
作者：
TOUATI, D;JACQUES, M;DESPIED, S
大肠杆菌皮毛蛋白，其铁（II）辅因子，抑制铁同化和锰超氧化物歧化酶（MnSOD）基因，从而耦合铁代谢，以保护免受氧毒性。铁同化在野生型细胞中由铁饥饿引发，并且在毛皮突变体中是组成性的。我们表明，铁代谢失调的毛皮突变体产生的铁超载，导致氧化应激和DNA损伤，包括致命的和诱变性病变。fur recA突变体在需氧条件下不能存活，并在从厌氧转变为需氧后死亡。通过铁螯合剂（ferrozine）、通过抑制三价铁转运（tonB突变体）或通过过度表达铁储存铁蛋白H样（FTN）蛋白来降低细胞内铁浓度消除氧敏感性。羟自由基清除剂二甲基亚砜和硫脲也提供了保护。功能性重组修复是保护所必需的，但不涉及SOS诱导。在毛皮突变体中，氧依赖性自发突变显著增加。同样，SOD缺乏使sodA sodB recA突变体在有氧条件下不可行。tonB突变抑制致死率，但铁螯合或过度表达FTN。因此，超氧化物介导的铁还原负责氧敏感性。此外，超氧化物歧化酶的过度表达部分保护fur recA突变体。我们建议，一个短暂的铁过载，这可能会产生氧化应激，发生在野生型细胞恢复正常生长条件下铁饥饿，与铁和MnSOD调节之间的耦合帮助细胞科普。
The Escherichia coli Fur protein, with its iron(II) cofactor, represses iron assimilation and manganese superoxide dismutase (MnSOD) genes, thus coupling iron metabolism to protection against oxygen toxicity. Iron assimilation is triggered by iron starvation in wild-type cells and is constitutive in fur mutants. We show that iron metabolism deregulation in fur mutants produces an iron overload, leading to oxidative stress and DNA damage including Lethal and mutagenic lesions. fur recA mutants were not viable under aerobic conditions and died after a shift from anaerobiosis to aerobiosis. Reduction of the intracellular iron concentration by an iron chelator (ferrozine), by inhibition of ferric iron transport (tonB mutants), or by overexpression of the iron storage ferritin H-like (FTN) protein eliminated oxygen sensitivity. Hydroxyl radical scavengers dimethyl sulfoxide and thiourea also provided protection. Functional recombinational repair was necessary for protection, but SOS induction was not involved. Oxygen-dependent spontaneous mutagenesis was significantly increased in fur mutants. Similarly, SOD deficiency rendered sodA sodB recA mutants nonviable under aerobic conditions. Lethality was suppressed by tonB mutations but not by iron chelation or overexpression of FTN. Thus, superoxide-mediated iron reduction was responsible for oxygen sensitivity. Furthermore, overexpression of SOD partially protected fur recA mutants. We propose that a transient iron overload, which could potentially generate oxidative stress, occurs in wild-type cells on return to normal growth conditions following iron starvation, with the coupling between iron and MnSOD regulation helping the cells cope.