Copper ions differ from other thiol reactive metal ions in their effects on the concentration and redox status of thiols in HeLa cell cultures

Abstract

Ions of metals such as copper, mercury, silver and cadmium are known to exhibit a high affinity for thiol groups and may therefore severely disturb many metabolic functions in the cell. Copper ions are also known to catalyse the formation of toxic oxygen species through a series of redox reactions. In the present study, we have determined the concentration of reduced and total glutathione, cysteine and homocysteine in a cell culture system (HeLa cell line) after addition of these metal ions. The main findings of the metal ion effect on the total thiol concentrations are that all metal ions increased the release of glutathione into the medium. Since the intracellular concentration of glutathione did not decrease under these conditions, the synthesis of glutathione must have been increased. In contrast to the other metal ions, copper ions also increased the release of homocysteine into the medium, possibly through interaction with S-adenosylhomocysteine hydrolase. The main findings of metal ion effects on reduced thiol are that, at concentrations not interfering with cell growth, mercury, silver and cadmium ions increased the concentration of extracellular reduced glutathione, possibly reflecting the increase of total glutathione in the medium. In contrast to the other metal ions, the addition of even very low amounts of copper ions (1 μmol/1) decreased the concentration of intra- and extracellular reduced thiols indicating oxidative stress.