Nitric oxide precipitates catastrophic chromosome fragmentation by bolstering both hydrogen peroxide and Fe(II) Fenton reactants in E. coli.
Nitric oxide precipitates catastrophic chromosome fragmentation by bolstering both hydrogen peroxide and Fe(II) Fenton reactants in E. coli.
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DOI：
10.1016/j.jbc.2022.101825
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发表时间：
2022-04
影响因子：
4.8
通讯作者：
Kuzminov, Andrei
中科院分区：
文献类型：
--
作者：
Agashe, Pooja;Kuzminov, Andrei
免疫细胞通过产生活性氧和氮物质来杀死入侵的微生物，主要是过氧化氢（H2 O2）和一氧化氮（NO）。我们以前发现，NO抑制大肠杆菌中的过氧化氢酶，稳定处理细胞周围的H2 O2，并通过连续的芬顿反应产生羟基自由基，促进灾难性的染色体断裂。事实上，单独的H2 O2处理杀死过氧化氢酶缺陷型（katEG）突变体类似于H2 O2 +NO处理。然而，除了H2 O2之外，芬顿反应还需要Fe（II），过量的H2 O2立即将Fe（II）转化为芬顿惰性的Fe（III）。对于连续芬顿，当H2 O2稳定时，还原铁的供应变得必要。在这里，我们表明，这种供应是由铁（II）招聘铁蛋白和铁（III）还原黄素还原酶确保。我们的观察结果也同意NO介导的呼吸抑制，驱动Fe（III）的还原。我们通过灭活ndh和nuo呼吸酶来模拟这种NO介导的抑制，这些呼吸酶负责NADH氧化的步骤，这导致增加的NADH池驱动黄素还原。我们发现，与katEG突变体一样，ndh nuo双突变体对H2 O2-单独和H2 O2 +NO处理同样敏感。此外，四重katEG ndh nuo突变体缺乏过氧化氢酶和有效的呼吸迅速杀死H2 O2-单独，但这种杀伤延迟NO，而不是增强它。两者合计，我们得出结论，NO提高了H2 O2和Fe（II）芬顿反应物的水平，使连续的羟基自由基的生产可行，并导致染色体不可挽回的氧化损伤。
Immune cells kill invading microbes by producing reactive oxygen and nitrogen species, primarily hydrogen peroxide (H2O2) and nitric oxide (NO). We previously found that NO inhibits catalases in Escherichia coli, stabilizing H2O2 around treated cells and promoting catastrophic chromosome fragmentation via continuous Fenton reactions generating hydroxyl radicals. Indeed, H2O2-alone treatment kills catalase-deficient (katEG) mutants similar to H2O2+NO treatment. However, the Fenton reaction, in addition to H2O2, requires Fe(II), which H2O2 excess instantly converts into Fenton-inert Fe(III). For continuous Fenton when H2O2 is stable, a supply of reduced iron becomes necessary. We show here that this supply is ensured by Fe(II) recruitment from ferritins and Fe(III) reduction by flavin reductase. Our observations also concur with NO-mediated respiration inhibition that drives Fe(III) reduction. We modeled this NO-mediated inhibition via inactivation of ndh and nuo respiratory enzymes responsible for the step of NADH oxidation, which results in increased NADH pools driving flavin reduction. We found that, like the katEG mutant, the ndh nuo double mutant is similarly sensitive to H2O2-alone and H2O2+NO treatments. Moreover, the quadruple katEG ndh nuo mutant lacking both catalases and efficient respiration was rapidly killed by H2O2-alone, but this killing was delayed by NO, rather than potentiated by it. Taken together, we conclude that NO boosts the levels of both H2O2 and Fe(II) Fenton reactants, making continuous hydroxyl-radical production feasible and resulting in irreparable oxidative damage to the chromosome.
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影响因子：
3.5
作者：
Clark, D;Durner, J;Klessig, DF
通讯作者：
Klessig, DF
DOI：
10.1016/j.mrfmmm.2003.07.002
发表时间：
2003-10-29
影响因子：
2.3
作者：
Bjelland, S;Seeberg, E
通讯作者：
Seeberg, E
影响因子：
3.9
作者：
Hurst, RD;Clark, JB
通讯作者：
Clark, JB
影响因子：
7.4
作者：
Amatore, Christian;Arbault, Stephane;Koh, Alaric C. W.
通讯作者：
Koh, Alaric C. W.
影响因子：
3.2
作者：
Amatore, Christian;Arbault, Stephane;Koh, Alaric C. W.
通讯作者：
Koh, Alaric C. W.