COPPER IONS DIFFER FROM OTHER THIOL REACTIVE METAL-IONS IN THEIR EFFECTS ON THE CONCENTRATION AND REDOX STATUS OF THIOLS IN HELA-CELL CULTURES

Ions of metals such as copper, mercury, silver and cadmium are known t o exhibit a high affinity for thiol groups and may therefore severely disturb many metabolic functions in the cell. Copper ions are also kno wn to catalyse the formation of toxic oxygen species through a series of redox reactions. In the present study, we have determined the conce ntration of reduced and total glutathione, cysteine and homocysteine i n 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 co ncentrations are that all metal ions increased the release of glutathi one into the medium. Since the intracellular concentration of glutathi one did not decrease under these conditions, the synthesis of glutathi one must have been increased. In contrast to the other metal ions, cop per ions also increased the release of homocysteine into the medium, p ossibly through interaction with S-adenosylhomocysteine hydrolase. The main findings of metal ion effects on reduced thiol are that, at conc entrations not interfering with cell growth, mercury, silver and cadmi um ions increased the concentration of extracellular reduced glutathio ne, possibly reflecting the increase of total glutathione in the mediu m. In contrast to the other metal ions, the addition of even very low amounts of copper ions (1 mu mol/l) decreased the concentration of int ra- and extracellular reduced thiols indicating oxidative stress. (C) 1997 Elsevier Science Ireland Ltd.