Home >> Redox Report, Volume 14, Number 2

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

Authors: Cerchiaro, Giselle1; Bolin, Celeste2; Cardozo-Pelaez, Fernando2

Source: Redox Report, Volume 14, Number 2, April 2009 , pp. 82-92(11)

Publisher: Maney Publishing

Buy & download fulltext article:

OR

Price: $48.00 plus tax (Refund Policy)

Abstract:

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 (oxo8GTP), 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 hydroxyl radical (HO•) is produced via oxidation of Cu+ to Cu2+ while in a complex with GTP. This HO• production is dependent on the availability of oxygen and the presence of GTP in the reaction milieu. Verification of free radical-mediated production of oxo8GTP 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 Cu2+ and L-ascorbic acid. A better understanding of the chemistry involved in this oxidative modification of GTP facilitates a more comprehensive understanding of its potential physiological consequences.

Keywords: GUANOSINE; COPPER; FREE RADICALS; GUANOSINE TRIPHOSPHATE; ASCORBATE; HYDROXYL RADICAL; OXIDATIVE STRESS; GTP

Document Type: Research Article

DOI: http://dx.doi.org/10.1179/135100009X392520

Affiliations: 1: Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André-SP, Brazil 2: Department of Biomedical and Pharmaceutical Sciences, Center for Environmental Health Sciences and Center for Structural and Functional Neurosciences, University of Montana, Missoula, Montana, USA

Publication date: 2009-04-01

Related content
Marked list

Tools

Key

Free Content
Free content
New Content
New content
Open Access Content
Open access content
Subscribed Content
Subscribed content
Free Trial Content
Free trial content

Text size:

A | A | A | A
^ Back to top
Share this item with others: These icons link to social bookmarking sites where readers can share and discover new web pages. print icon Print this page