The role of glutathione transferases in cadmium stress.
Using Saccharomyces cerevisiae as experimental model, we observed that cells mutated in the GTT1 or GTT2 genes showed twice as much cadmium absorption than the control strain. We proposed that the formation of the cadmium-glutathione complex is dependent on that transferase, since it was previously demonstrated that the cytoplasmic levels of this complex affect cadmium uptake. The addition of glutathione monoethyl ester (GME), a drug that mimics glutathione (GSH), to gtt1Delta cells restored the levels of metal absorption to those of the control strain. However, with respect to gtt2Delta cells, addition of GME did not alter the capacity of removing cadmium from the medium. Taken together, these results suggest that Gtt1 and Gtt2 play different roles in the mechanism of cadmium detoxification. By analyzing the toxic effect of this metal, we verified that gtt2Delta and gsh1Delta cells showed, respectively, higher and lower tolerance to cadmium stress than control cells, suggesting that although GSH plays a relevant role in cell protection, formation of the GSH-Cd conjugate is deleterious to the mechanism of defense.
Departamento de Bioquímica, IQ, UFRJ, Rio de Janeiro, RJ, Brazil.
Paula D B
PD
Adamis
Débora S
DS
Gomes
Maria Lucia C C
ML
Pinto
Anita D
AD
Panek
Elis C A
EC
Eleutherio
D002104:Cadmium / Q000378:metabolism / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism*; D016296:Mutagenesis; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology / Q000235:genetics
D009153:Mutagens; D012333:RNA, Messenger; D002104:Cadmium; C042431:S-ethyl glutathione; D005982:Glutathione Transferase; D005978:Glutathione