title: Redox-active complexes formed during the interaction between glutathione and mercury and/or copper ions.
abstract: 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.
authors.affiliation: Facultad de Química, Pontificia Universidad Católica de Chile, Santiago, Chile. mealiaga@uc.cl
authors.forename: Margarita E
authors.initials: ME
authors.lastname: Aliaga
authors.forename: Camilo
authors.initials: C
authors.lastname: López-Alarcón
authors.forename: Germán
authors.initials: G
authors.lastname: Barriga
authors.forename: Claudio
authors.initials: C
authors.lastname: Olea-Azar
authors.forename: Hernán
authors.initials: H
authors.lastname: Speisky
mesh_terms: D000082:Acetaminophen / Q000737:chemistry / Q000378:metabolism; D000465:Algorithms; D003300:Copper / Q000737:chemistry* / Q000378:metabolism; D045304:Cytochromes c / Q000737:chemistry / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D004996:Ethidium / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D005978:Glutathione / Q000737:chemistry* / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008628:Mercury / Q000737:chemistry* / Q000378:metabolism; D008956:Models, Chemical; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D011485:Protein Binding
chemical_list: D009942:Organometallic Compounds; C067883:dihydroethidium; D000082:Acetaminophen; D003300:Copper; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D004996:Ethidium; D008628:Mercury; D005978:Glutathione