Modification of the Amino Group of Guanosine by Methylglyoxal and Other .ALPHA.-Ketoaldehydes in the Presence of Hydrogen Peroxide.

Nukaya, Haruo; Inaoka, Yasunori; Ishida, Hideyuki; Tsuji, Kiichiro; Suwa, Yoshihide; Wakabayashi, Keiji; Kosuge, Takuo

doi:10.1248/cpb.41.649

Cited by 27 publications

(18 citation statements)

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“…The mutagenicity of methylglyoxal was improved markedly in the presence of hydrogen peroxide. This was associated with the formation of N 2 -acetyldeoxyguanosine in DNA [26][27][28].…”

Section: Dna Glycation Mutagenesis and Ner (Nucleotide Excision Repair)mentioning

confidence: 99%

Protecting the genome: defence against nucleotide glycation and emerging role of glyoxalase I overexpression in multidrug resistance in cancer chemotherapy

Thornalley

2003

Biochemical Society Transactions

116

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Glycation of nucleotides in DNA forms AGEs (advanced glycation end-products). Nucleotide AGEs are: the imidazopurinone derivative dG-G [3-(2'-deoxyribosyl)-6,7-dihydro-6,7-dihydroxyimidazo[2,3-b]purin-9(8)one], CMdG ( N (2)-carboxymethyldeoxyguanosine) and gdC (5-glycolyldeoxycytidine) derived from glyoxal, dG-MG [6,7-dihydro-6,7-dihydroxy-6-methylimidazo-[2,3-b]purine-9(8)one], dG-MG(2) [ N (2),7-bis-(1-hydroxy-2-oxopropyl)deoxyguanosine] and CEdG [ N (2)-(1-carboxyethyl)deoxyguanosine] derived from methylglyoxal, and dG-3DG [ N (2)-(1-oxo-2,4,5,6-tetrahydroxyhexyl)deoxyguanosine] derived from 3-deoxyglucosone and others. Glyoxal and methylglyoxal induce multi-base deletions, and base-pair substitutions - mostly occurring at G:C sites with G:C-->C:G and G:C-->T:A transversions. Suppression of nucleotide glycation by glyoxalase I and aldehyde reductases and dehydrogenases, and base excision repair, protects and recovers DNA from damaging glycation. The effects of DNA glycation may be most marked in diabetes and uraemia. Mutations arising from DNA glycation may explain the link of non-dietary carbohydrate intake to incidence of colorectal cancer. Overexpression of glyoxalase I was found in drug-resistant tumour cells and may be an example of an undesirable effect of the enzymatic protection against DNA glycation. Experimental overexpression of glyoxalase I conferred resistance to drug-induced apoptosis. Glyoxalase I-mediated drug resistance was found in human leukaemia and lung carcinoma cells. Methylglyoxal-mediated glycation of DNA may contribute to the cytotoxicity of some antitumour agents as a consequence of depletion of NAD(+) by poly(ADP-ribose) polymerase, marked increases in triosephosphate concentration and increased formation of methylglyoxal. S - p -Bromobenzylglutathione cyclopentyl diester is a cell-permeable glyoxalase I inhibitor. It countered drug resistance and was a potent antitumour agent against lung and prostate carcinoma. Glyoxalase I overexpression was also found in invasive ovarian cancer and breast cancer.

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“…The mutagenicity of methylglyoxal was improved markedly in the presence of hydrogen peroxide. This was associated with the formation of N 2 -acetyldeoxyguanosine in DNA [26][27][28].…”

Section: Dna Glycation Mutagenesis and Ner (Nucleotide Excision Repair)mentioning

confidence: 99%

Protecting the genome: defence against nucleotide glycation and emerging role of glyoxalase I overexpression in multidrug resistance in cancer chemotherapy

Thornalley

2003

Biochemical Society Transactions

116

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“…[1][2][3] Methylglyoxal is an endogenous metabolite. 4) Moreover, it was identified as a precursor of AGE [5][6][7] which accumulates in the plasma of uremic patients at a reported concentration of 1.53Ϯ0.25 mM. 8) This compound is known to react with the guanidino group in proteins 4,7,9,10) and it binds and reversibly modifies arginine residues.…”

mentioning

confidence: 99%

“…4) Moreover, it was identified as a precursor of AGE [5][6][7] which accumulates in the plasma of uremic patients at a reported concentration of 1.53Ϯ0.25 mM. 8) This compound is known to react with the guanidino group in proteins 4,7,9,10) and it binds and reversibly modifies arginine residues. [11][12][13] The reactions have been shown to occur even at physiological concentrations of methylglyoxal.…”

mentioning

confidence: 99%

Generation of Superoxide Anions during the Reaction of Guanidino Compounds with Methylglyoxal.

Nohara

Usui

Kinoshita

et al. 2002

CHEMICAL & PHARMACEUTICAL BULLETIN

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Uremic toxins are accumulated in the blood of patients with chronic renal failure (CRF), although alteration of the toxicity by the interaction of various uremic retention products has not been precisely clarified. In this study, we found that cytochrome c added to incubation mixtures containing guanidino compounds and methylglyoxal in phosphate buffer solution (pH 7.4) resulted in reduction of cytochrome c. Superoxide anions were generated from incubation mixtures of each guanidino compound with methylglyoxal, because the reduction was inhibited by the addition of superoxide dismutase. The incubation mixture containing each guanidino compound and methylglyoxal had different rates of generation of the superoxide anion from other mixtures. A relatively higher superoxide anion formation rate was observed in the incubation mixture containing Arg and methylglyoxal (7.9؎0.5 nmol · m ؊1 · min ؊1 ), or in the incubation mixture containing methylguanidine and methylglyoxal (6.3؎0.6 nmol · ml ؊1 · min ؊1). These findings suggest that interactions of various uremic retention products which accumulate in the blood of uremic patients may generate reactive oxygen species and may be involved in the oxidative stress observed in CRF patients. The addition of aminoguanidine, which is known to inhibit the formation of advanced glycation end products, to a mixture of guanidino compounds and methylglyoxal inhibited reactions between guanidino compounds and methylglyoxal.

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“…117 Moulds Apesar de o metilglioxal existir sob tantas formas em água, a mais reativa é a ceto-aldeídica, segundo Nukaya e colaboradores (1993). 119 Esta é a forma produtora de ácido fórmico, ácido acético e diacetilo em meio aquoso tamponado com fosfato e H 2 O 2 diluído. Neste trabalho, detectou-se radical acetila e consequente formação de N-acetilguanosina, a qual poderia indicar uma atividade mutagênica do metilglioxal.…”

Section: Efeitos Citotóxicos E Tóxicos Do Metilglioxalunclassified

Metilglioxal: uma toxina endógena?

Sartori¹,

Bechara²

2010

Quím. Nova

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IS METHYLGLYOXAL AN ENDOGENOUS TOXIN?Methylglyoxal is a very reactive α-oxoaldehyde putatively produced by glycolysis, cytochrome P 450 -catalyzed acetone oxidation and aminoacetone oxidation. Methylglyoxal has been pointed as a substrate for the glyoxalase system ultimately energy-yielding pyruvate, but methylglyoxal is also a toxicant involved in protein aggregation and DNA modification. Controversial hypothesis on methylglyoxal as an anticancer agent, an energy-yielding glycolysis intermediates, and as a regulator of cell division have also been proposed. Methylglyoxal research focuses now on unveiling its biological properties and on the discovery of drugs capable to inhibit its toxic effects, principally in diabetes.

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Modification of the Amino Group of Guanosine by Methylglyoxal and Other .ALPHA.-Ketoaldehydes in the Presence of Hydrogen Peroxide.

Cited by 27 publications

References 2 publications

Protecting the genome: defence against nucleotide glycation and emerging role of glyoxalase I overexpression in multidrug resistance in cancer chemotherapy

Protecting the genome: defence against nucleotide glycation and emerging role of glyoxalase I overexpression in multidrug resistance in cancer chemotherapy

Generation of Superoxide Anions during the Reaction of Guanidino Compounds with Methylglyoxal.

Metilglioxal: uma toxina endógena?

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