Effect of some heavy metal ions on copper-induced metallothionein synthesis in the yeast Saccharomyces cerevisiae

Copper-induced metallothionein (MT) synthesis in Saccharomyces cerevisiae w as investigated in order to associate this exclusively with Cu2+ in vivo, w hen cultured in nutrient medium containing other heavy metal ions. Expressi on of the CUP1 promoter/lacZ fusion gene was inhibited by all heavy metal i ons tested, especially Cd2+ and Mn2+. By adding Cd2+ and Mn2+ at 10 mu M co ncentration, the beta-galactosidase activity decreased by about 80% and 50% of the maximum induction observed with 1 mM CuSO4, respectively. Furthermo re, cell growth was markedly inhibited by combinations of 1 mM-Cu2+ and 1 m u M-Cd2+. Therefore, the yeast S. cerevisiae could not rely on MT synthesis as one of the copper-resistance mechanisms, when grown in a Cd2+ environme nt. In contrast, the presence of Mn2+ in the nutrient medium showed allevia tion rather than growth inhibition by high concentrations of Cu2+. The reco very from growth inhibition by Mn2+ was due to decreased Cu2+ accumulation. Inhibitory concentrations of Co2+, Ni2+ and Zn2+ on expression of the CUP1 p/lacZ fusion gene were at least one order of magnitude higher than that of Cd2+ and Mn2+. These results are discussed in relation to Cu2+ transport a nd Cu-induced MT synthesis in the copper-resistance mechanism of the yeast S. cerevisiae.