Superoxide-dependent reduction of free Fe(3+) and release of Fe(2+) from ferritin by the physiologically-occurring Cu(I)-glutathione complex.
The intracellularly-occurring Cu(I)-glutathione complex (Cu(I)-[GSH](2)) has the ability to reduce molecular oxygen into superoxide radicals (O2·-). Based on such ability, we addressed the potential of this complex to generate the redox-active Fe(2+) species, during its interaction with free Fe(3+) and with ferritin-bound iron. Results show that: (i) the complex reduces free Fe(3+) through a reaction that totally depends on its O2·--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 O2·--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(2)O(2), the Fe(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](2) complex to generate the redox-active Fe(2+) species and suggest that by favouring the occurrence of superoxide-driven Fenton reactions, its pro-oxidant potential could be increased beyond its initial O2·--generating capacity.
Nutrition and Food Technology Institute, University of Chile, Macul 5540, Macul, POB 138-11, Santiago, Chile.
Margarita E
ME
Aliaga
Catalina
C
Carrasco-Pozo
Camilo
C
López-Alarcón
Claudio
C
Olea-Azar
Hernán
H
Speisky
D003300:Copper / Q000737:chemistry*; D005290:Ferric Compounds / Q000737:chemistry*; D005293:Ferritins / Q000737:chemistry*; D005296:Ferrous Compounds / Q000737:chemistry*; D005978:Glutathione / Q000737:chemistry*; D017665:Hydroxyl Radical / Q000737:chemistry; D010084:Oxidation-Reduction; D013481:Superoxides / Q000737:chemistry*
D005290:Ferric Compounds; D005296:Ferrous Compounds; D013481:Superoxides; D017665:Hydroxyl Radical; D003300:Copper; D005293:Ferritins; D005978:Glutathione