Nucleotides function as endogenous chemical sensors for oxidative stress signaling

Hideshi Ihara, Tomohiro Sawa, Yusaku Nakabeppu, Takaaki Akaike

研究成果: ジャーナルへの寄稿総説査読

17 被引用数 (Scopus)


Oxidized and nitrated nucleotides including 8-oxogunanine and 8-nitroguanine derivatives such as 8-nitroguanosine 3′,5′-cyclic monophosphate were generated by reactive nitrogen oxides and reactive oxygen species in cultured cells and in tissues. 8-oxoguanine and 8-nitroguanine in DNA and RNA are potentially mutagenic, and the former also induces cell death. Some derivative, 8-nitroguanosine 3′,5′-cyclic monophosphate a major nitrated guanine nucleotide, was identified as a novel second messenger. Surprisingly, the amount of 8-nitroguanosine 3′,5′-cyclic monophosphate generated was found to be higher than that of guanosine 3′,5′-cyclic monophosphate in cells expressing inducible nitric oxide synthase. More important, 8-nitroguanosine 3′,5′-cyclic monophosphate is electrophilic and reacted efficiently with sulf-hydryls of proteins to produce a novel posttranslational modification (named S-guanylation) via guanosine 3′,5′-cyclic monophosphate adduction. For example, 8-nitroguanosine 3′,5′-cyclic monophosphate-induced S-guanylation of Kelch-like ECH-associated protein 1 led to NF-E2-related factor activation and induction of antioxidant enzymes. 8-nitroguanosine 3′,5′-cyclic monophosphate may thus protect cells against oxidative stress-related cytotoxicity. Therefore, although chemically modified nucleotides produced via oxidative and nitrative stress are regarded simply as endogenous mutagens, the endogenous nucleotides stored in cells per se may serve functionally as a sensing mechanism for reactive nitrogen oxides and oxygen species to induce cellular adaptive responses to oxidative stress.

ジャーナルJournal of Clinical Biochemistry and Nutrition
出版ステータス出版済み - 1月 2011

!!!All Science Journal Classification (ASJC) codes

  • 医学(その他)
  • 栄養および糖尿病
  • 臨床生化学


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