Potassium channel activation by glutathione-S-conjugates in Escherichia coli: protection against methylglyoxal is mediated by cytoplasmic acidification.
Escherichia coli possesses two glutathione-gated potassium channels, KefB and KefC, that are activated by glutathione-S-conjugates formed with methylglyoxal. We demonstrate that activation of the channels leads to cytoplasmic acidification and that this protects cells during electrophilic attack. Further, we demonstrate that mutants lacking the channels can be protected against the lethal effects of methylglyoxal by acidification of the cytoplasm with a weak acid. The degree of protection is determined by the absolute value of the pHi and the time at which acidification takes place. Alterations in the pHi do not accelerate the rate of detoxification of methylglyoxal. The mechanism by which methylglyoxal causes cell death and the implications for pHi-mediated resistance to methylglyoxal are discussed.
Ferguson
G P
GP
Department of Molecular and Cell Biology, University of Aberdeen, Marischal College, UK.
McLaggan
D
D
Booth
I R
IR
D000085:Acetates / Q000494:pharmacology; D019342:Acetic Acid; D017920:Antiporters / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003593:Cytoplasm / Q000737:chemistry; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism; D029968:Escherichia coli Proteins; D005978:Glutathione / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D007424:Intracellular Fluid / Q000737:chemistry; D018384:Oxidative Stress; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D027961:Potassium-Hydrogen Antiporters; D011522:Protons; D011765:Pyruvaldehyde / Q000494:pharmacology*
D000085:Acetates; D017920:Antiporters; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D015221:Potassium Channels; D027961:Potassium-Hydrogen Antiporters; D011522:Protons; C069287:KefC protein, E coli; D011765:Pyruvaldehyde; D005978:Glutathione; D019342:Acetic Acid; D011188:Potassium