Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 33-39 |
| Number of pages | 7 |
| Journal | Journal of Clinical Biochemistry and Nutrition |
| Volume | 48 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 1 2011 |
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All Science Journal Classification (ASJC) codes
- Medicine (miscellaneous)
- Nutrition and Dietetics
- Clinical Biochemistry
Cite this
Nucleotides function as endogenous chemical sensors for oxidative stress signaling. / Ihara, Hideshi; Sawa, Tomohiro; Nakabeppu, Yusaku; Akaike, Takaaki.
In: Journal of Clinical Biochemistry and Nutrition, Vol. 48, No. 1, 01.01.2011, p. 33-39.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Nucleotides function as endogenous chemical sensors for oxidative stress signaling
AU - Ihara, Hideshi
AU - Sawa, Tomohiro
AU - Nakabeppu, Yusaku
AU - Akaike, Takaaki
PY - 2011/1/1
Y1 - 2011/1/1
N2 - 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.
AB - 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.
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U2 - 10.3164/jcbn.11-003FR
DO - 10.3164/jcbn.11-003FR
M3 - Review article
VL - 48
SP - 33
EP - 39
JO - Journal of Clinical Biochemistry and Nutrition
JF - Journal of Clinical Biochemistry and Nutrition
SN - 0912-0009
IS - 1
ER -