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.


CONCLUSIONS
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+).
Barbier
Olivier
O
Unité Mixte de Recherche, Centre National de la Recherche Scientifique 6548, Université de Nice-Sophia Antipolis, Nice, France.
Dauby
Angélique
A
Jacquillet
Grégory
G
Tauc
Michel
M
Poujeol
Philippe
P
Cougnon
Marc
M
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002104:Cadmium / Q000493:pharmacokinetics*; D002460:Cell Line; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D007700:Kinetics; D008657:Metabolic Clearance Rate; D011817:Rabbits; D015032:Zinc / Q000493:pharmacokinetics*
D002104:Cadmium; D015032:Zinc