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

Tomohiro Sawa; Takaaki Akaike; Koji Ichimori; Teruo Akuta; Kazuyoshi Kaneko; Hitoshi Nakayama; Dennis J. Stuehr; Hiroshi Maeda

doi:10.1016/j.bbrc.2003.10.003

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

Tomohiro Sawa, Takaaki Akaike, Koji Ichimori, Teruo Akuta, Kazuyoshi Kaneko, Hitoshi Nakayama, Dennis J. Stuehr, Hiroshi Maeda

MED - Public Health

Research output: Contribution to journal › Article › peer-review

53 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	300-306
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	311
Issue number	2
DOIs	https://doi.org/10.1016/j.bbrc.2003.10.003
Publication status	Published - 2003 Nov 14

Keywords

8-Nitroguanosine
NADPH-dependent reductase
Nitrative stress
Nitric oxide
Nitric oxide synthase
Reactive nitrogen oxides
Superoxide

Access to Document

10.1016/j.bbrc.2003.10.003

Cite this

@article{2830b1192fc946d38e86109d284de598,

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

abstract = "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.",

keywords = "8-Nitroguanosine, NADPH-dependent reductase, Nitrative stress, Nitric oxide, Nitric oxide synthase, Reactive nitrogen oxides, Superoxide",

author = "Tomohiro Sawa and Takaaki Akaike and Koji Ichimori and Teruo Akuta and Kazuyoshi Kaneko and Hitoshi Nakayama and Stuehr, {Dennis J.} and Hiroshi Maeda",

note = "Funding Information: This work was supported by a Grant-in-Aid for Scientific Research from the Japan Promotion of Science, a Grant-in-Aid on Priority Area from the Ministry of Education, Culture, Sports, Science and Technology, and a grant for Cancer Research from the Ministry of Health, Labor and Welfare of Japan to T.A. We thank T. Yoshimura for reading the manuscript and Judith B. Gandy for her excellent editing of the manuscript. Thanks are also due to K. Sasamoto for his help in preparing the molecular orbit model of 8-nitroguanosine.",

year = "2003",

month = nov,

day = "14",

doi = "10.1016/j.bbrc.2003.10.003",

language = "English",

volume = "311",

pages = "300--306",

journal = "Biochemical and Biophysical Research Communications",

issn = "0006-291X",

publisher = "Academic Press Inc.",

number = "2",

}

TY - JOUR

T1 - Superoxide generation mediated by 8-nitroguanosine, a highly redox-active nucleic acid derivative

AU - Sawa, Tomohiro

AU - Akaike, Takaaki

AU - Ichimori, Koji

AU - Akuta, Teruo

AU - Kaneko, Kazuyoshi

AU - Nakayama, Hitoshi

AU - Stuehr, Dennis J.

AU - Maeda, Hiroshi

N1 - Funding Information: This work was supported by a Grant-in-Aid for Scientific Research from the Japan Promotion of Science, a Grant-in-Aid on Priority Area from the Ministry of Education, Culture, Sports, Science and Technology, and a grant for Cancer Research from the Ministry of Health, Labor and Welfare of Japan to T.A. We thank T. Yoshimura for reading the manuscript and Judith B. Gandy for her excellent editing of the manuscript. Thanks are also due to K. Sasamoto for his help in preparing the molecular orbit model of 8-nitroguanosine.

PY - 2003/11/14

Y1 - 2003/11/14

N2 - 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.

AB - 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.

KW - 8-Nitroguanosine

KW - NADPH-dependent reductase

KW - Nitrative stress

KW - Nitric oxide

KW - Nitric oxide synthase

KW - Reactive nitrogen oxides

KW - Superoxide

UR - http://www.scopus.com/inward/record.url?scp=0242362832&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0242362832&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2003.10.003

DO - 10.1016/j.bbrc.2003.10.003

M3 - Article

C2 - 14592413

AN - SCOPUS:0242362832

SN - 0006-291X

VL - 311

SP - 300

EP - 306

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 2

ER -

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

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this