Details

Autor(en) / Beteiligte

• Aliaga, Margarita E
• Carrasco-Pozo, Catalina
• Lopez-Alarcon, Camilo
• Olea-Azar, Claudio
• Speisky, Hernan

Titel

Superoxide-dependent reduction of free Fe super(3+) and release of Fe super(2+) from ferritin by the physiologically-occurring Cu(I)-glutathione complex

Ist Teil von

• Bioorganic & medicinal chemistry, 2011-01, Vol.19 (1), p.534-541

Erscheinungsjahr

2011

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• The intracellularly-occurring Cu(I)-glutathione complex (Cu(I)-[GSH] sub(2)) has the ability to reduce molecular oxygen into superoxide radicals (). Based on such ability, we addressed the potential of this complex to generate the redox-active Fe super(2+) species, during its interaction with free Fe super(3+) and with ferritin-bound iron. Results show that: (i) the complex reduces free Fe super(3+) through a reaction that totally depends on its [inline image]-generating capacity; (ii) during its interaction with ferritin, the complex reduces and subsequently releases iron through a largely (77%) SOD-inhibitable reaction; the remaining fraction is accounted for by a direct effect of GSH molecules contained within the complex. The [inline image]-dependent iron-releasing efficiency of the complex was half that of its iron-reducing efficiency; (iii) the ability of the complex to release ferritin-bound iron was increased, concentration-dependently, by the addition of GSH and totally prevented by SOD; (iv) in the presence of added H sub(2)O sub(2), the Fe super(2+) ions generated through (i) or (ii) were able to catalyze the generation of hydroxyl radicals. Thus, the present study demonstrates the ability of the Cu(I)-[GSH] sub(2) complex to generate the redox-active Fe super(2+) species and suggest that by favouring the occurrence of superoxide-driven Fenton reactions, its pro-oxidant potential could be increased beyond its initial [inline image]-generating capacity.