Diphenyl Diselenide Protects against Methylmercury-Induced Toxicity in Saccharomyces cerevisiae via the Yap1 Transcription Factor.

Abstract

Methylmercury (MeHg) is a ubiquitous and persistent environmental pollutant that induces serious neurotoxic effects. Diphenyl diselenide [(PhSe)2], an organoseleno compound, exerts protective effects against MeHg toxicity, although the complete mechanism remains unclear. The aim of this study was to investigate the mechanisms involved in the protective effect of (PhSe)2 on the toxicity induced by MeHg using wild-type Saccharomyces cerevisiae and mutants with defects in enzymes and proteins of the antioxidant defense system (yap1Δ, ybp1Δ, ctt1Δ, cat1Δ, sod1Δ, sod2Δ, gsh1Δ, gsh2Δ, gtt1Δ, gtt2Δ, gtt3Δ, gpx1Δ, gpx2Δ, trx1Δ, trx2Δ, trx3Δ, and trr2Δ). In the wild-type strain, (PhSe)2 protected against the growth inhibition, reactive oxygen species production, and decrease in membrane integrity induced by MeHg and restored thiol levels to values indistinguishable from the control. Single deletions of yap1, sod1, sod2, gsh1, gsh2, gpx1, gpx2, trx1, trx2, and trx3 decreased the capacity of (PhSe)2 to prevent MeHg toxicity in yeast, indicating their involvement in (PhSe)2 protection. Together, these results suggest a role of (PhSe)2 in modulating the gene expression of antioxidant enzymes and ABC transporters through the action of the transcription factor YAP1, preventing the oxidative damage caused by MeHg in S. cerevisiae.