Apoptosis as a mechanism for removal of mutated cells of Saccharomyces cerevisiae: the role of Grx2 under cadmium exposure.
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.
Gomes
Débora Silva
DS
Departamento de Bioquímica, Instituto de Química, UFRJ, 21941-909, Rio de Janeiro, RJ, Brazil.
Pereira
Marcos Dias
MD
Panek
Anita Dolly
AD
Andrade
Leonardo Rodrigues
LR
Eleutherio
Elis Cristina Araújo
EC
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*
D019187:Cadmium Compounds; D054477:Glutaredoxins; C527885:Grx2 protein, S cerevisiae; D009153:Mutagens; D029701:Saccharomyces cerevisiae Proteins; D013431:Sulfates; C037123:cadmium sulfate; D005978:Glutathione