Generation of Superoxide by the Interaction Between Mercury Ions and Endogenous Thiols

Aliaga, Margarita; Vásquez-Arce, Alexis; López-Alarcón, Camilo; Olea Azar, Claudio; Barriga, Germán; Speisky, Hernán; Kim, Ki-Hyun; Brown, Richard J. C.

Abstract

The interaction between Hg2+ ions and endogenous thiols (RSH), such as glutathione (GSH), cysteine (Cys), homocysteine (Hcy), cysteinyl-glycine (CysGly) and -glutamyl-cysteine (-GluCys), leads to the swift formation of the Hg(II)-thiol complexes. We investigated the potential capacity of Hg(II)-[RSH] and Hg(II)-[RSH]2 complexes to reduce oxygen into superoxide. Among these complexes, only Hg(II)-[GSH]2, Hg(II)-[Cys]2 and Hg(II)-[Hcy] were able to reduce oxygen in a concentration-dependent manner. The generation of the superoxide induced by these complexes was confirmed by EPR spin-trapping. Further evidence on the ability of the complexes to generate superoxide was attained through the demonstration of their capacities to reduce cytochrome c and/or to oxidize dyhydroethidium (two superoxide-susceptible probes), both effects being SOD-inhibitable. In the case of the solutions containing either Hg(II)-[CysGly]n or Hg(II)-[-GluCys]n (n = 1 or 2) no redox activity toward molecular oxygen was observed. The incubation of the complexes Hg(II)-[GSH]2, Hg(II)-[Cys]2 and Hg(II)-[Hcy] with oxygen during 60 min led to the hydrogen peroxide-dependent oxidation of acetaminophen (inhibited by catalase) and an increment in the formation of their oxidized thiols (oxidized glutathione, cystine and homocystine, respectively). Thus, the ability of the complexes to generate superoxide and, thereby, to deleteriously affect superoxide-susceptible biological targets warrants further studies.

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Fecha de publicación: 2013
Página de inicio: 87
Página final: 98
Idioma: English