Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 16, Issue 13, Pages 6568-6574Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2008.05.026
Keywords
copper-glutathione complex; glutathione; superoxide radicals; copper; redox-activity
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Cu2+ ions and GSH molecules interact to swiftly form the complex Cu(I)-glutathione. We investigated the potential capacity of such complex to reduce molecular oxygen. The addition of SOD to a solution containing Cu(I)-glutathione led to a sustained decline of the basal oxygen level. Such effect was partially reverted by the addition of catalase. The complex was able to induce the reduction of cytochrome c and the oxidation of dyhydroethidium into 2-hydroxyethidium. Both effects were totally blocked by SOD. The ability of the complex to generate superoxide radicals was confirmed by EPR spin-trapping. Cu(I)-glutathione induce no oxidation of fluorescein, a hydroxyl radical-sensitive probe. We conclude that in solutions containing the complex, oxygen is continually reduced into superoxide, and that-in absence of interceptors-the latter radicals are quantitatively re-oxidized into molecular oxygen. We suggest that by functioning as a continuous source of superoxide, the complex could potentially affect a broad range of susceptible biological targets. (c) 2008 Elsevier Ltd. All rights reserved.
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