Renal type II Na/Pi-cotransporter is strongly impaired whereas the Na/sulphate-cotransporter and aquaporin 1 are unchanged in cadmium-treated rats.
The cellular mechanisms of cadmium (Cd) nephrotoxicity are poorly understood. In this study we investigated the cellular causes of the Cd-induced phosphaturia in the rat. Compared to controls, Cd-treated rats (2 mg Cd/kg body weight, s.c. for 14 days) showed a marked polyuria, proteinuria and phosphaturia. As studied by the rapid filtration technique in isolated cortical brush-border membrane vesicles (BBMV), Na+-gradient-driven uptake of phosphate ([32Pi]) and of [3H] glucose were markedly decreased in Cd-treated rats, whereas uptake of sulphate ([35S]) remained unchanged. By Western blotting of BBMV proteins and by indirect immunocytochemistry in 4-micron thick frozen fixed kidney sections, using an antibody against the type II Na/Pi-cotransporter (NaPi-2), we found a diminished expression of this protein in the brush-border membrane from Cd-treated rats. How ever, the expression of the water channel aquaporin 1, estimated from the specific antibody staining in brush-border membranes, remained unchanged by Cd. Northern blot analysis showed a strong reduction of 2.7 kb NaPi-2-related mRNA in Cd-affected kidneys. Our data indicate that: (1) Cd may reduce reabsorption of Pi in proximal tubules by affecting the expression of the functional Na/Pi-cotransporters in the luminal membrane, and (2) Cd effects on brush-border transporters are selective.
Herak-Kramberger
C M
CM
Institute for Medical Research and Occupational Health, Ksaverska cesta 2, PO Box 291, 10000 Zagreb, Croatia.
Spindler
B
B
Biber
J
J
Murer
H
H
Sabolić
I
I
D000818:Animals; D051398:Aquaporin 1; D020346:Aquaporins; D015152:Blotting, Northern; D015153:Blotting, Western; D002104:Cadmium / Q000494:pharmacology*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D027682:Cation Transport Proteins; D007150:Immunohistochemistry; D007473:Ion Channels / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007672:Kidney Cortex / Q000201:enzymology / Q000378:metabolism*; D008871:Microvilli / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000077003:Sodium Sulfate Cotransporter; D050608:Sodium-Phosphate Cotransporter Proteins; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D027981:Symporters
C496022:Aqp1 protein, rat; D020346:Aquaporins; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D007473:Ion Channels; D000077003:Sodium Sulfate Cotransporter; D050608:Sodium-Phosphate Cotransporter Proteins; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D027981:Symporters; D002104:Cadmium; D051398:Aquaporin 1