Regulatory effects of zinc and copper on the calcium transport system in rat liver nuclei. Relation to SH groups in the releasing mechanism.

In isolated hepatic nuclei, the heavy metals Zn2+ and Cu2+ (10 microM) inhibited Ca2+ uptake and caused a prompt release of Ca2+ from preloaded nuclei in a concentration-dependent manner, with Zn2+ being more effective than Cu2+. The sulfhydryl group reducing agent dithiothreitol (DTT) protected the nuclei from the effects of heavy metals; DDT (1 mM) almost completely blocked Zn(2+)- or Cu(2+)-induced Ca2+ release and inhibition of Ca2+ uptake. The sulfhydryl modifying reagent N-ethylmaleimide (NEM; 0.2 mM) also caused Ca2+ release, but it did not have an appreciable effect on Ca2+ uptake. Furthermore, in the presence of NEM heavy metals did not evoke Ca2+ release. The present study demonstrates that Zn2+ and Cu2+ have a stimulatory effect on Ca2+ release from isolated rat liver nuclei, and that the SH group may play an important role in the Ca(2+)-releasing mechanism in liver nuclei.