title: Sodium nitroprusside may modulate Escherichia coli antioxidant enzyme expression by interacting with the ferric uptake regulator.
abstract: Efforts to explore possible relationships between nitric oxide (NO) and antioxidant enzymes in an Escherichia coli model have uncovered a possible interaction between sodium nitroprusside (SNP), a potent, NO-donating drug, and the ferric uptake regulator (Fur), an iron(II)--dependent regulator of antioxidant and iron acquisition proteins present in Gram-negative bacteria. The enzymatic profiles of superoxide dismutase and hydroperoxidase during logarithmic phase of growth were studied via non-denaturing polyacrylamide gel electrophoresis and activity staining specific to each enzyme. Though NO is known to induce transcription of the manganese-bearing isozyme of SOD (MnSOD), treatment with SNP paradoxically suppressed MnSOD expression and greatly enhanced the activity of the iron-containing equivalent (FeSOD). Fur, one of six global regulators of MnSOD transcription, is uniquely capable of suppressing MnSOD while enhancing FeSOD expression through distinct mechanisms. We thus hypothesize that Fur is complacent in causing this behaviour and that the iron(II) component of SNP is activating Fur. E. coli was also treated with the SNP structural analogues, potassium ferricyanide (PFi) and potassium ferrocyanide (PFo). Remarkably, the ferrous PFo was capable of mimicking the SNP-related pattern, whereas the ferric PFi was not. As Fur depends upon ferrous iron for activation, we submit this observation of redox-specificity as preliminary supporting evidence for the hypothesized Fur-SNP interaction. Iron is an essential metal that the human innate immune system sequesters to prevent its use by invading pathogens. As NO is known to inhibit iron-bound Fur, and as activated Fur regulates iron uptake through feedback inhibition, we speculate that the administration of this drug may disrupt this strategic management of iron in favour of residing Gram-negative species by providing a source of iron in an otherwise iron-scarce environment capable of encouraging its own uptake. However, these gains may be counteracted by the oxidative consequences of iron and NO, as the former can catalyse the formation of toxic free radical species while the latter can inhibit enzymes and contribute to the formation of other toxic compounds. The potential consequences of SNP on microbial growth warrant future investigation.
authors: Department of Chemistry, University of Winnipeg, Winnipeg, Manitoba, Canada R3B 2E9.
authors: R
authors: R
authors: Bertrand
authors: D
authors: D
authors: Danielson
authors: V
authors: V
authors: Gong
authors: B
authors: B
authors: Olynik
authors: M O
authors: MO
authors: Eze
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D005292:Ferricyanides / Q000494:pharmacology; D005295:Ferrocyanides / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology*; D012097:Repressor Proteins / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D005292:Ferricyanides; D005295:Ferrocyanides; D012097:Repressor Proteins; C068477:ferric uptake regulating proteins, bacterial; D009599:Nitroprusside; D009569:Nitric Oxide; D002374:Catalase; C051253:katG protein, E coli; D013482:Superoxide Dismutase; C031835:potassium ferrocyanide; C028033:potassium ferricyanide