Alkyl hydroperoxide reductase subunit C (AhpC) protects bacterial and human cells against reactive nitrogen intermediates.
In Salmonella typhimurium, ahpC encodes subunit C of alkyl hydroperoxide reductase, an enzyme that reduces organic peroxides. Here, we asked if ahpC could protect cells from reactive nitrogen intermediates (RNI). Salmonella disrupted in ahpC became hypersusceptible to RNI. ahpC from either Mycobacterium tuberculosis or S. typhimurium fully complemented the defect. Unlike protection against cumene hydroperoxide, protection afforded by ahpC against RNI was independent of the reducing flavoprotein, AhpF. Mycobacterial ahpC protected human cells from necrosis and apoptosis caused by RNI delivered exogenously or produced endogenously by transfected nitric oxide synthase. Resistance to RNI appears to be a physiologic function of ahpC. ahpC is the most widely distributed gene known that protects cells directly from RNI, and provides an enzymatic defense against an element of antitubercular immunity.
Chen
L
L
Seaver Laboratory, Department of Medicine, Cornell University Medical College, New York, New York 10021, USA.
Xie
Q W
QW
Nathan
C
C
D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D003603:Cytotoxins / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology; D029968:Escherichia coli Proteins; D015964:Gene Expression Regulation, Bacterial; D015971:Gene Expression Regulation, Enzymologic; D005816:Genetic Complementation Test; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009584:Nitrogen / Q000378:metabolism*; D009603:Nitroso Compounds / Q000494:pharmacology; D009876:Operon / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology*; D010088:Oxidoreductases / Q000235:genetics* / Q000378:metabolism*; D010544:Peroxidases; D010545:Peroxides / Q000378:metabolism; D054464:Peroxiredoxins; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D026422:S-Nitrosoglutathione; D012486:Salmonella typhimurium / Q000201:enzymology; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000201:enzymology
D001426:Bacterial Proteins; D003603:Cytotoxins; D029968:Escherichia coli Proteins; D009603:Nitroso Compounds; D010545:Peroxides; D010975:Platelet Aggregation Inhibitors; D017382:Reactive Oxygen Species; D026422:S-Nitrosoglutathione; D010088:Oxidoreductases; D010544:Peroxidases; D054464:Peroxiredoxins; C515937:ahpC protein, E coli; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C515938:ahpF protein, E coli; D005978:Glutathione; D009584:Nitrogen