Zinc and cadmium interactions in a renal cell line derived from rabbit proximal tubule

Background: The aim of this work was to characterize the relationship between zinc (Zn(2+)) and cadmium (Cd(2+)) and the toxic effects of Cd(2+) in immortalized renal proximal tubule cells RP1.

Methods: An RP1 cell line was developed from primary cultures of microdissected S1 and S2. Uptakes of (65)Zn and (109)Cd and competitive experiments with Cd(2+) and Zn(2+) were performed and kinetic parameters were determined. Oxygen consumption, metallothionein synthesis, and necrotic and apoptotic phenomena were studied.

Results: Kinetic parameters indicate that (65)Zn (Km = 71.8 +/- 10.6 microM) and (109)Cd (Km = 23.3 +/- 2.0 microM) were both transported by a saturable carrier-mediated process. Competition between Cd(2+) and Zn(2+) uptake was reciprocal. Cd(2+) induced an increase in necrosis and apoptosis, and a decrease in oxygen consumption, depending on Cd(2+) concentrations. Concomitant addition of Zn(2+) (10 microM) reduced the number of necrotic and apoptotic cells and maintained oxygen consumption at control levels. Cd(2+) alone, or in the presence of Zn(2+), increased metallothionein levels, whereas Zn(2+) alone did not.

Conclusion: Zn(2+) and Cd(2+) probably share the same transporter in the proximal tubule. Cd(2+) caused necrotic and apoptotic cell death. Cd(2+) toxicity may occur through an effect on the mitochondrial electron transport chain and not on metallothionein synthesis. Zn(2+) protects against the renal cell toxicity of Cd(2+).