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Cadmium Transport Mechanisms in the Proximal Tubule
Author(s) -
Wang Yanhua,
Zalups Rudolfs,
Barfuss Delon W
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a544-a
Subject(s) - chemistry , cadmium , cystine , cysteine , biophysics , verapamil , biochemistry , stereochemistry , calcium , biology , organic chemistry , enzyme
The lumen‐to‐cell transport, cellular accumulation, and toxicity of ionic cadmium ( 109 Cd 2+ ) and cadmium‐cysteine conjugate (Cys‐S‐ 109 Cd‐S‐Cys) were studied in isolated perfused segments of the proximal tubule of rabbit kidneys. When a 0.73μM Cd 2+ or 0.73μM Cys‐S‐ 109 Cd‐S‐Cys containing solution was perfused there was no visual evidence of acute toxicity; blebbing of the luminal membrane, cellular vital dye uptake, and cellular swelling. Cd 2+ transport was temperature dependent (87% reduction at 22°C and 100% at 11°C) and inhibited by high Ca 2+ concentrations (27% reduction with 1.95mM and 69% with 2.6mM), FeCl 2 (42% reduction with 10μM) and ZnCl 2 (48% reduction with 20μM). The Cd 2+ transport was not affected by verapamil and diltiazem. The Cys‐S‐Cd‐S‐Cys transport was also temperature dependent (76% reduction at 22°C and 100% at 11°C) and inhibited by L‐cystine and L‐arginine (55% and 57% respectively), but stimulated by L‐methionine (56%), and not affected by L‐aspartate, L‐glutamate, and Gly‐sar. 2, 3‐Dimercaptopropane‐1‐Sulfonate (DMPS) in the perfusate decreased absorption of Cd 2+ (39% reduction with 30 μM and 95% reduction with 200 μM), while DMPS in the bath had no effect on the transport. We conclude that cadmium can be transported at the luminal membrane by multiple mechanisms depending on its form. Ionic cadmium appears to be transported by an iron transporter (DCT1?) and the zinc transporter (ZTL1) and DMPS appears to chelate cadmium. The cadmium conjugate of L‐cysteine appears to be transported by a L‐cystine transporter (system b° ,+ ). Calcium channels and dipeptide transporters are not involved in cadmium transport.