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

摘要

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 (Co~(2+), Cd~(2+), Zn~(2+), Pb~(2+), Al~(3+), Hg~(2+) and Ni~(2+)) on the superoxide-generating capacity of such complex was investigated. Amongst all tested metals, only Hg~(2+) was able to substantially affect the capacity of Cu(I)-[GSH]_2 to generate superoxide. When Hg~(2+) 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 Hg~(2+) for GSH and the observed ability of Hg~(2+) to lower the concentration of Cu(I)-[GSH]_2 (spectroscopically assessed), we suggest that Hg~(2+) 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 Hg~(2+)-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.