Nitrosative stress: activation of the transcription factor OxyR.
Hydrogen peroxide (H2O2) imposes an oxidative stress to Escherichia coli that is manifested by oxidation of glutathione and related redox-sensitive targets. OxyR is a thiol-containing transcriptional activator whose oxidation controls the expression of genes involved in H2O2 detoxification. Here we report that certain S-nitrosothiols (RSNOs) impose what we term a "nitrosative stress" to E. coli, evidenced by lowering of intracellular thiol and the transcriptional activation of OxyR by S-nitrosylation. This cellular and genetic response determines the metabolic fate of RSNOs and thereby contributes to bacterial rescue from stasis. Our studies reveal that signaling by S-nitrosylation can extend to the level of transcription and describe a metabolic pathway that constitutes an adaptation to nitrosative stress.
Hausladen
A
A
Department of Medicine, Duke University Medical Center Durham, North Carolina 27710, USA.
Privalle
C T
CT
Keng
T
T
DeAngelo
J
J
Stamler
J S
JS
D000332:Aerobiosis; D000693:Anaerobiosis; D002374:Catalase / Q000378:metabolism; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D004268:DNA-Binding Proteins; D004790:Enzyme Induction / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects / Q000502:physiology; D005978:Glutathione / Q000032:analysis / Q000502:physiology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008623:Mercaptoethanol; D009569:Nitric Oxide / Q000494:pharmacology; D009603:Nitroso Compounds / Q000378:metabolism / Q000494:pharmacology*; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D012097:Repressor Proteins / Q000378:metabolism*; D026403:S-Nitrosothiols; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology*
D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D009603:Nitroso Compounds; D016877:Oxidants; D012097:Repressor Proteins; D026403:S-Nitrosothiols; D014157:Transcription Factors; C499299:oxyR protein, E coli; D009569:Nitric Oxide; D008623:Mercaptoethanol; C032635:S-nitrosomercaptoethanol; C021315:S-nitrosocysteine; D006861:Hydrogen Peroxide; D002374:Catalase; C051253:katG protein, E coli; D005978:Glutathione; D003545:Cysteine