Enhanced resistance of yeast mutants deficient in low-affinity iron and zinc transporters to stannous-induced toxicity

Abstract

Tin or stannous (Sn(2+)) compounds are used as catalysts, stabilizers in plastic industries, wood preservatives, agricultural biocides and nuclear medicine. In order to verify the Sn(2+) up-take and toxicity in yeast cells we utilized a multi-elemental analysis known as particle-induced X-ray emission (PIXE) along with cell survival assays and quantitative real-time PCR. The detection of Sn(2+) by PIXE was possible only in yeast cells in stationary phase of growth (STAT cells) that survive at 25mM Sn(2+) concentration. Yeast cells in exponential phase of growth (LOG cells) tolerate only micro-molar Sn(2+) concentrations that result in intracellular concentration below of the method detection limit. Our PIXE analysis showed that STAT XV185-14c yeast cells demonstrate a significant loss of intracellular elements such as Mg, Zn, S, Fe and an increase in P levels after 1h exposure to SnCl(2). The survival assay showed enhanced tolerance of LOG yeast cells lacking the low-affinity iron and zinc transporters to stannous treatment, suggesting the possible involvement in Sn(2+) uptake. Moreover, our qRT-PCR data showed that Sn(2+) treatment could generate reactive oxygen species as it induces activation of many stress-response genes, including SOD1, YAP1, and APN1.