Cadmium perturbs calcium homeostasis in rat osteosarcoma (ros 17/2.8) cells; a possible role for protein kinase c

Abstract

The mechanism of the toxic effects of Cd 2+ on bone cell function is not completely understood at this time. This study was designed to characterize the effect of Cd 2+ on Ca 2+ metabolism in ROS 17/2.8 cells. Cells were labeled with 45Ca (1.87 mM Ca) for 20 h in the presence of 0.01, 0.1, or 1.0 μM Cd 2+ and kinetic parameters were determined from 45a efflux curves. Three kinetic compartments described the intracellular metabolism of 45Ca. Cd 2+ (0.01 μM) caused an approximate 9 × increase in Ca 2+ flux across the plasma membrane and a decrease in the most rapidly exchanging intracellular Ca 2 1 compartment (S 1). However, there was no change in total cell Ca 2+, indicating an increased cycling of Ca 2+ across the plasma membrane. Flux between S 1, and the intermediate Ca 2+ compartment (83) was also increased and S 2 increased significantly. All Cd 2+ induced changes in Ca 2+ homeostasis were obliterated by concurrent treatment with 0.1 μM calphostin C (CC), a potent protein kinase C (PKC) inhibitor. This data suggests that Cd 2+ perturbs Ca 2+ metabolism via a PKC dependent process.