Superoxide generation mediated by 8-nitroguanosine, a highly redox-active nucleic acid derivative

被引：47

作者：

Sawa, T

Akaike, T ^{[1
]}

Ichimori, K

Akuta, T

Kaneko, K

Nakayama, H

Stuehr, DJ

Maeda, H

机构：

[1] Kumamoto Univ, Grad Sch Med & Pharmaceut Sci, Dept Microbiol, Kumamoto 8608556, Japan

[2] Kumamoto Univ, Grad Sch Med & Pharmaceut Sci, Dept Mol Cell Funct, Kumamoto 8608556, Japan

[3] Natl Inst Adv Ind Sci & Technol, Human Stress Signal Res Ctr, Ikeda, Osaka 5638577, Japan

[4] Cleveland Clin Fdn, Lerner Res Inst, Dept Immunol, Cleveland, OH 44195 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2003年 / 311卷 / 02期

关键词：

8-nitroguanosine; nitric oxide; superoxide; nitric oxide synthase; NADPH-dependent reductase; reactive nitrogen oxides; nitrative stress;

D O I：

10.1016/j.bbrc.2003.10.003

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2003 Elsevier Inc. All rights reserved.

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页码：300 / 306

页数：7

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