Krapp A R, Tognetti V B, Carrillo N, Acevedo A
Molecular Biology Division, PROMUBIE, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Argentina.
Eur J Biochem. 1997 Oct 15;249(2):556-63. doi: 10.1111/j.1432-1033.1997.00556.x.
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.
铁氧化还原蛋白-NADP⁺还原酶（FNR）参与细胞对氧化损伤的防御。缺乏FNR的大肠杆菌突变体对甲基紫精和过氧化氢异常敏感。通过在突变细胞中表达植物FNR、超氧化物歧化酶或过氧化氢酶基因，可恢复对这些氧化剂的耐受性。根据相关突变菌株所表现出的表型判断，在氧化还原循环条件下，FNR对协同防御紫精毒性的贡献与大肠杆菌两种主要超氧化物歧化酶的贡献相似。然而，在sodA sodB菌株中表达FNR未能提高它们对紫精的耐受性，这表明FNR的作用靶点不是超氧阴离子自由基。缺乏FNR的细胞对氧化剂的敏感性与广泛的DNA损伤有关。用铁螯合剂或羟自由基清除剂处理突变细菌可显著保护其免受紫精或过氧化物的损伤，这表明缺乏FNR的细胞中的氧化损伤是由细胞内铁通过原位形成羟自由基介导的。还原酶的NADP（H）依赖性活性对于解毒是必要且充分的，在此过程中无需铁氧化还原蛋白或黄素氧化还原蛋白的参与。文中讨论了FNR可能发挥其保护作用的潜在机制。
