Zinc and Cadmium Interactions in a Renal Cell Line Derived from Rabbit Proximal Tubule

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 µ M) and ¹⁰⁹Cd (Km = 23.3 ± 2.0 µ M) 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 µ M) 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⁺.