title: The role of ferredoxin-NADP+ reductase in the concerted cell defense against oxidative damage -- studies using Escherichia coli mutants and cloned plant genes.
abstract: Ferredoxin-NADP+ reductases (FNR) participate in cellular defense against oxidative damage. Escherichia coli mutants deficient in FNR are abnormally sensitive to methyl viologen and hydrogen peroxide. Tolerance to these oxidants was regained by expression of plant FNR, superoxide dismutase, or catalase genes in the mutant cells. FNR contribution to the concerted defense against viologen toxicity under redox-cycling conditions was similar to that of the two major E. coli superoxide dismutases together, as judged by the phenotypes displayed by relevant mutant strains. However, FNR expression in sodA sodB strains failed to increase their tolerance to viologens, indicating that the FNR target is not the superoxide radical. Sensitivity of FNR-deficient cells to oxidants is related to extensive DNA damage. Incubation of the mutant bacteria with iron chelators or hydroxyl radical scavengers provided significant protection against viologens or peroxide, suggesting that oxidative injury in FNR-deficient cells was mediated by intracellular iron through the formation of hydroxyl radicals in situ. The NADP(H)-dependent activities of the reductase were necessary and sufficient for detoxification, without participation of either ferredoxin or flavodoxin in the process. Possible mechanisms by which FNR may exert its protective role are discussed.
authors.affiliation: Molecular Biology Division, PROMUBIE, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Argentina.
authors.forename: A R
authors.initials: AR
authors.lastname: Krapp
authors.forename: V B
authors.initials: VB
authors.lastname: Tognetti
authors.forename: N
authors.initials: N
authors.lastname: Carrillo
authors.forename: A
authors.initials: A
authors.lastname: Acevedo
mesh_terms: D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D002374:Catalase / Q000096:biosynthesis / Q000378:metabolism; D002736:Chloroplasts / Q000201:enzymology; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D029968:Escherichia coli Proteins; D005287:Ferredoxin-NADP Reductase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D017343:Genes, Plant; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007506:Iron-Sulfur Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D018551:Solanum lycopersicum / Q000201:enzymology / Q000235:genetics; D008954:Models, Biological; D008961:Models, Structural; D018384:Oxidative Stress / Q000502:physiology*; D010100:Oxygen / Q000633:toxicity; D010269:Paraquat / Q000494:pharmacology; D018532:Pisum sativum / Q000201:enzymology / Q000235:genetics; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; C060704:FNR protein, E coli; D007506:Iron-Sulfur Proteins; D011994:Recombinant Proteins; D006861:Hydrogen Peroxide; D002374:Catalase; C095500:SodA protein, Bacteria; C087504:SodB protein, Bacteria; D013482:Superoxide Dismutase; D005287:Ferredoxin-NADP Reductase; D010269:Paraquat; D010100:Oxygen