Cadmium perturbs calcium homeostasis in rat osteosarcoma (ROS 17/2.8) cells; a possible role for protein kinase C.
The mechanism of the toxic effects of Cd2+ on bone cell function is not completely understood at this time. This study was designed to characterize the effect of Cd2+ on Ca2+ metabolism in ROS 17/2.8 cells. Cells were labeled with (45)Ca (1.87 mM Ca) for 20 h in the presence of 0.01, 0.1, or 1.0 microM Cd2+ and kinetic parameters were determined from (45)Ca efflux curves. Three kinetic compartments described the intracellular metabolism of (45)Ca. Cd2+ (0.01 microM) caused an approximate 9 x increase in Ca2+ flux across the plasma membrane and a decrease in the most rapidly exchanging intracellular Ca2+ compartment (S1). However, there was no change in total cell Ca2+, indicating an increased cycling of Ca2+ across the plasma membrane. Flux between S1 and the intermediate Ca2+ compartment (S2) was also increased and S2 increased significantly. All Cd2+ induced changes in Ca2+ homeostasis were obliterated by concurrent treatment with 0.1 microM calphostin C (CC), a potent protein kinase C (PKC) inhibitor. This data suggests that Cd2+ perturbs Ca2+ metabolism via a PKC dependent process.
Long
G J
GJ
Department of Biology, Olivet Nazarene University, Kankakee, IL 60901, USA.
D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects*; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D009281:Naphthalenes / Q000494:pharmacology; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D009281:Naphthalenes; D002104:Cadmium; D011493:Protein Kinase C; C058819:calphostin C; D002118:Calcium