Ferguson G P, Battista J R, Lee A T, Booth I R
Department of Molecular and Cell Biology, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
Mol Microbiol. 2000 Jan;35(1):113-22. doi: 10.1046/j.1365-2958.2000.01682.x.
The effect of the toxic metabolite methylglyoxal on the DNA of Escherichia coli cells has been investigated. Exposure of E. coli cells to methylglyoxal reduces the transformability of plasmid DNA and results in the degradation of genomic DNA. The activity of the KefB and KefC potassium channels protects E. coli cells against methylglyoxal and limits the amount of DNA damage. In mutants lacking KefB and KefC, methylglyoxal-induced DNA damage was reduced by incubation with a weak acid that lowers the pHi to the same extent as through KefB and KefC activation. This provides evidence that acidification of the cytoplasm protects E. coli DNA against methylglyoxal. By the analysis of cells lacking UvrA, we demonstrate that this repair protein is required for the degradation of the DNA upon methylglyoxal exposure. However, protection by KefB and KefC occurred independently of UvrA. Although we present evidence that exposure of E. coli cells to methylglyoxal results in DNA degradation, our results suggest this event is not essential for methylglyoxal-induced death. The implications of these findings will be discussed.
已对有毒代谢产物甲基乙二醛对大肠杆菌细胞DNA的影响进行了研究。将大肠杆菌细胞暴露于甲基乙二醛会降低质粒DNA的转化能力，并导致基因组DNA的降解。KefB和KefC钾通道的活性可保护大肠杆菌细胞免受甲基乙二醛的影响，并限制DNA损伤的量。在缺乏KefB和KefC的突变体中，通过与一种弱酸孵育可减少甲基乙二醛诱导的DNA损伤，该弱酸将细胞内pH值降低到与通过KefB和KefC激活相同的程度。这提供了证据表明细胞质酸化可保护大肠杆菌DNA免受甲基乙二醛的影响。通过对缺乏UvrA的细胞进行分析，我们证明这种修复蛋白是甲基乙二醛暴露后DNA降解所必需的。然而，KefB和KefC的保护作用独立于UvrA发生。尽管我们提供的证据表明大肠杆菌细胞暴露于甲基乙二醛会导致DNA降解，但我们的结果表明这一事件对于甲基乙二醛诱导的死亡并非必不可少。将讨论这些发现的意义。
