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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Hydroxyl radical oxidation of guanosine 5 `-triphosphate (GTP): requirement for a GTP-Cu(II) complex

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Autor(es):
Cerchiaro, Giselle [1] ; Bolin, Celeste [2, 3] ; Cardozo-Pelaez, Fernando [2, 3]
Número total de Autores: 3
Afiliação do(s) autor(es):
[1] Univ Fed ABC, Ctr Ciencias Nat & Humanas, Santo Andre, SP - Brazil
[2] Univ Montana, Dept Biomed & Pharmaceut Sci, Ctr Environm Hlth Sci, Missoula, MT 59812 - USA
[3] Univ Montana, Ctr Struct & Funct Neurosci, Missoula, MT 59812 - USA
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: Redox Report; v. 14, n. 2, p. 82-92, APR 2009.
Citações Web of Science: 7
Resumo

Levels of oxidized guanosine base in DNA have become a hallmark biomarker in assessing oxidative stress implicated in a variety of disease and toxin-induced states. However, there is evidence that the guanosine in the nucleotide triphosphate pool (GTP) is more susceptible to oxidation than guanosine residues incorporated into nucleic acids and this causes a substantial amount of the oxidized product, 8-oxoguanosine 5'-triphosphate (oxo(8)GTP), to accumulate in cell-free and in cell-culture preparations. Electron paramagnetic resonance (EPR) spectroscopy and direct EPR analysis of free radical production by copper sulfate and L-ascorbic acid demonstrates that the hydroxy. radical (HO(center dot)) is produced via oxidation of Cu(+) to Cu(2+) while in a complex with GTP. This HO(center dot) production is dependent on the availability of oxygen and the presence of GTP in the reaction milieu. Verification of free radical-mediated production of oxo(8)GTP is presented using HPLC with electrochemical detection and matrix-assisted laser desorption/ionization linear time-of-flight mass spectrometry (MALDI-LTOF-MS). The sum of these results is presented in a novel mechanism of GTP oxidation by Cu(2+) and L-ascorbic acid. A better understanding of the chemistry involved in this oxidative modification of GTP facilitates a more comprehensive understanding of its potentia. physiological consequences. (AU)

Processo FAPESP: 07/50765-2 - Estudo de processos oxidativos e radicalares envolvendo o cobre no meio biológico: uma investigação de mecanismos moleculares da atividade oxidante de complexos e proteínas contendo cobre
Beneficiário:Giselle Cerchiaro
Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores