Differential Regulation of Copper and Zinc Metabolism in Rat Liver Parenchymal Cells in Primary Cultures 1

Abstract

A variety of factors influence copper and zinc metabolism in primary cultures of rat hepatocytes. Pronounced elevations in accumulated ⁶⁴Cu were produced by incubating cells with either Cu²⁺ or epinephrine with moderate increases produced by incubation with cycloheximide, actinomycin D, or dexamethasone. In addition, copper accumulation was enhanced when cells received culture medium more highly enriched in amino acids and other nutrients. Hepatocytes accumulate greater quantities of ⁶⁵Zn when incubated with dexamethasone or high extracellular zinc. Higher levels of metallothionein were found in cells incubated with either dexamethasone, zinc, or copper but not with epinephrine. However, epinephrine was effective in elevating ceruloplasmin levels in the cell cytosol. Incubation with dexamethasone or copper-containing medium resulted in elevated ³H-ceruloplasmin in both cytosol and medium. Data presented suggest hormones influence copper and zinc metabolism in liver parenchymal cells in a differential fashion.