Superoxide generation mediated by 8-nitroguanosine, a highly redox-active nucleic acid derivative.
Formation of 8-nitroguanosine may be characterized as nucleic acid modification induced by nitric oxide (NO). We show here that 8-nitroguanosine is a highly redox-active nucleic acid derivative that strongly stimulated superoxide generation from various NADPH-dependent reductases, including cytochrome P450 reductase and all isoforms of NO synthase. This reaction involves these reductases in a redox cycling reaction via single-electron reduction of 8-nitroguanosine to form 8-nitroguanosine anion radical. One electron is then transferred from this radical to molecular oxygen. 8-Nitroguanosine formed in vivo may function as a potent redox cofactor that intensifies oxyradical generation by various NADPH/reductase-like enzymes and thus participates in diverse physiological and pathological events.
Department of Microbiology, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
Tomohiro
T
Sawa
Takaaki
T
Akaike
Koji
K
Ichimori
Teruo
T
Akuta
Kazuyoshi
K
Kaneko
Hitoshi
H
Nakayama
Dennis J
DJ
Stuehr
Hiroshi
H
Maeda
D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry*; D006151:Guanosine / Q000031:analogs & derivatives / Q000737:chemistry*; D007527:Isoenzymes / Q000737:chemistry; D009249:NADP / Q000737:chemistry; D009251:NADPH-Ferrihemoprotein Reductase / Q000737:chemistry*; D019001:Nitric Oxide Synthase / Q000737:chemistry*; D009574:Nitro Compounds / Q000737:chemistry*; D009696:Nucleic Acids / Q000737:chemistry; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry*; D013481:Superoxides / Q000138:chemical synthesis*
C095838:8-nitroguanine; C481144:8-nitroguanosine; D007527:Isoenzymes; D009574:Nitro Compounds; D009696:Nucleic Acids; D013481:Superoxides; D006151:Guanosine; D009249:NADP; D006147:Guanine; D019001:Nitric Oxide Synthase; D009251:NADPH-Ferrihemoprotein Reductase; D010100:Oxygen