Pro-oxidant action of diphenyl diselenide in the yeast Saccharomyces cerevisiae exposed to ROS-generating conditions.
Organoselenium compounds have a potential thiol peroxidase-like activity. Diphenyl diselenide (DPDS) is an electrophilic reagent used in the synthesis of a variety of pharmacologically active organic selenium compounds. Using TRAP assay of chemiluminescense we have shown that diphenyl diselenide clearly possesses a pro-oxidant property. For an investigation on the mechanisms of this property, we used mutant strains of Saccharomyces cerevisiae defective in antioxidant defenses, i.e. in superoxide dismutase, in biosynthesis of glutathione, and the transcription factor yAP-1-lacking yap 1 mutant that cannot activate genes of the oxidative stress response. Exposure of growing cultures to the drug increased cell sensitivity to oxidizing agents. The pro-oxidant effect was independent of the metabolic condition or of the oxidative mutagen tested. N-acetylcysteine, a precursor of glutathione biosynthesis, could neutralize the pro-oxidant effects of diphenyl diselenide by stimulating an increase of endogenous glutathione biosynthesis or by directly binding to the drug. Vitamin E (Trolox), a known antioxidant, was also able to protect S. cerevisiae against the pro-oxidant effect of diphenyl diselenide. In vitro assays showed that diphenyl diselenide interacts non-enzymatically with the thiol group of glutathione.
Moreira Rosa
Renato
R
Centro de Biotecnologia/Departamento de Biofísica, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brasil.
de Oliveira
Ramatis Birnfeld
RB
Saffi
Jenifer
J
Braga
Antônio Luís
AL
Roesler
Rafael
R
Dal-Pizzol
Felipe
F
Fonseca Moreira
José Cláudio
JC
Brendel
Martin
M
Pêgas Henriques
João Antonio
JA
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001555:Benzene Derivatives / Q000037:antagonists & inhibitors / Q000633:toxicity*; D001761:Bleomycin / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects; D005285:Fermentation; D016166:Free Radical Scavengers / Q000494:pharmacology; D005800:Genes, Fungal / Q000235:genetics; D005978:Glutathione / Q000378:metabolism; D008163:Luminescent Measurements; D008165:Luminol / Q000737:chemistry; D009154:Mutation / Q000502:physiology; D016566:Organoselenium Compounds / Q000037:antagonists & inhibitors / Q000633:toxicity*; D016877:Oxidants / Q000633:toxicity*; D010100:Oxygen / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology
D000964:Antimetabolites, Antineoplastic; D001555:Benzene Derivatives; D016166:Free Radical Scavengers; D016566:Organoselenium Compounds; D016877:Oxidants; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; D001761:Bleomycin; D014810:Vitamin E; C061132:diphenyldiselenide; D008165:Luminol; D013482:Superoxide Dismutase; D005978:Glutathione; D010100:Oxygen