title: Apoptosis as a mechanism for removal of mutated cells of Saccharomyces cerevisiae: the role of Grx2 under cadmium exposure.
abstract: Cadmium is a strong mutagen that acts by inhibiting DNA mismatch repair, while its toxic effect seems to be related to an indirect oxidative stress that involves glutathione (GSH) mobilization. Among the roles of GSH is the protection of proteins against oxidative damage, by forming reversible mixed disulfides with cysteine residues, a process known as protein glutathionylation and catalyzed by glutaredoxins (Grx). In this current study, Saccharomyces cerevisiae cells deficient in GRX2, growing in 80 muM CdSO(4), showed high mitochondrial mutagenic rate, determined by frequency of mutants that had lost mitochondrial function (petite mutants), high tolerance and lower apoptosis induction. The mutant strain also showed decreased levels of glutathionylated-protein after cadmium exposure, which might difficult the signaling to apoptosis, leading to increased mutagenic rates. Taken together, these results suggest that Grx2 is involved with the apoptotic death induced by cadmium, a form of cellular suicide that might lead of removal of mutated cells.
authors.affiliation: Departamento de Bioquímica, Instituto de Química, UFRJ, 21941-909, Rio de Janeiro, RJ, Brazil.
authors.forename: Débora Silva
authors.initials: DS
authors.lastname: Gomes
authors.forename: Marcos Dias
authors.initials: MD
authors.lastname: Pereira
authors.forename: Anita Dolly
authors.initials: AD
authors.lastname: Panek
authors.forename: Leonardo Rodrigues
authors.initials: LR
authors.lastname: Andrade
authors.forename: Elis Cristina Araújo
authors.initials: EC
authors.lastname: Eleutherio
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D019187:Cadmium Compounds / Q000633:toxicity*; D054477:Glutaredoxins / Q000235:genetics / Q000502:physiology*; D005978:Glutathione / Q000378:metabolism; D009153:Mutagens / Q000633:toxicity*; D010084:Oxidation-Reduction; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D013431:Sulfates / Q000633:toxicity*
chemical_list: D019187:Cadmium Compounds; D054477:Glutaredoxins; C527885:Grx2 protein, S cerevisiae; D009153:Mutagens; D029701:Saccharomyces cerevisiae Proteins; D013431:Sulfates; C037123:cadmium sulfate; D005978:Glutathione