Redox-active complexes formed during the interaction between glutathione and mercury and/or copper ions

Prompted by the recently reported capacity of the physiologically occurring Cu(I)–[glutathione]2 complex (Cu(I)–[GSH)]2) to reduce oxygen, the effect of various GSH-binding metals (Co2+, Cd2+, Zn2+, Pb2+, Al3+, Hg2+ and Ni2+) on the superoxide-generating capacity of such complex was investigated. Amongst all tested metals, only Hg2+ was able to substantially affect the capacity of Cu(I)–[GSH]2 to generate superoxide. When Hg2+ and Cu(I)–[GSH]2 were mixed equimolarly, the superoxide formation, assessed through the cytochrome c reduction and dihydroethidium oxidation, was increased by over 50%. Such effect was totally inhibitable by SOD. Based on the reportedly higher affinity of Hg2+ for GSH and the observed ability of Hg2+ to lower the concentration of Cu(I)–[GSH]2 (spectroscopically assessed), we suggest that Hg2+ displaces Cu(I) from Cu(I)–[GSH]2, to release Cu(I) ions and form a Hg(II)–[GSH]2 complex. The latter species would account for the Hg2+-induced exacerbation of the superoxide production. In fact, the present study provides first time evidence that a preformed Hg(II)–[GSH]2 complex is able to concentration-dependently reduce oxygen. Such redox-activity was evidenced using cytochrome c and confirmed by EPR studies using DMPO (5,5-dimethyl-1-pyrroline N-oxide, a spin-trapping agent). Considering this novel ability of Hg(II)–[GSH]2 to generate superoxide, a further characterization of its redox-activity and its potential to affect superoxide-susceptible biological targets appears warranted.

Hg2+ increases the ability of Cu(I)–[GSH]2 to generate superoxide. Formation of a redox-active Hg(II)–[GSH]2 complex is suggested.Figure optionsDownload as PowerPoint slide