Abstract
Background: The aim of this work was to characterize the relationship between zinc (Zn2+) and cadmium (Cd2+) and the toxic effects of Cd2+ in immortalized renal proximal tubule cells RP1. Methods: An RP1 cell line was developed from primary cultures of microdissected S1 and S2. Uptakes of 65Zn and 109Cd and competitive experiments with Cd2+ and Zn2+ were performed and kinetic parameters were determined. Oxygen consumption, metallothionein synthesis, and necrotic and apoptotic phenomena were studied. Results: Kinetic parameters indicate that 65Zn (Km = 71.8 ± 10.6 µM) and 109Cd (Km = 23.3 ± 2.0 µM) were both transported by a saturable carrier-mediated process. Competition between Cd2+ and Zn2+ uptake was reciprocal. Cd2+ induced an increase in necrosis and apoptosis, and a decrease in oxygen consumption, depending on Cd2+ concentrations. Concomitant addition of Zn2+ (10 µM) reduced the number of necrotic and apoptotic cells and maintained oxygen consumption at control levels. Cd2+ alone, or in the presence of Zn2+, increased metallothionein levels, whereas Zn2+ alone did not. Conclusion: Zn2+ and Cd2+ probably share the same transporter in the proximal tubule. Cd2+ caused necrotic and apoptotic cell death. Cd2+ toxicity may occur through an effect on the mitochondrial electron transport chain and not on metallothionein synthesis. Zn2+ protects against the renal cell toxicity of Cd2+.