Details

Autor(en) / Beteiligte

• Aliaga, Margarita E.
• López-Alarcón, Camilo
• García-Río, Luis
• Martín-Pastor, Manuel
• Speisky, Hernán

Titel

Redox-changes associated with the glutathione-dependent ability of the Cu(II)–GSSG complex to generate superoxide

Ist Teil von

• Bioorganic & medicinal chemistry, 2012-05, Vol.20 (9), p.2869-2876

Ort / Verlag

Amsterdam: Elsevier Ltd

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• The intracellularly-occurring Cu(I)–glutathione complex (Cu(I)–[GSH]2) has the ability to reduce molecular oxygen into superoxide. Removal of such radicals leads to the irreversible conversion of Cu(I)–[GSH]2 into the redox-inactive Cu(II)–GSSG complex. The present study addressed the potential of reduced glutathione, ascorbate and superoxide to reductively regenerate Cu(I)–[GSH]2 from Cu(II)–GSSG, and investigated the redox changes involved in such process. Results show that: (i) among the three tested reductants, only GSH is able to reduce the Cu(II) bound to GSSG; (ii) during the reduction of Cu(II)–GSSG, a Cu(I)–GSSG intermediate would be formed (supported here by Cu(I) and GSSG recovery data and by NMR studies); (iii) when GSH is present in a molar excess equal or greater than 1:3, the reduction of Cu(II)–GSSG into Cu(I)–[GSH]2 is quantitative and complete. Under such conditions, the Cu(II)–GSSG complex acquires a superoxide-generating capacity which is identical to that seen with the Cu(I)–[GSH]2 complex. Within cells, the concentrations of GSH are at least 2- to 3-fold order of magnitude higher than those expected for the Cu(II)–GSSG complex. Thus, we postulate that the interaction between GSH and Cu(II)–GSSG could be seen as a potential mechanism to regenerate continuously the Cu(I)–[GSH]2 complex and thereby affect the ability of the latter to generate superoxide.