engleski

Loss of brush-border proteins in cadmium-induced nephrotoxicity in rat

Background and purpose: Nephropathy due to chronic cadmium (Cd) exposure in man and experimental animals is manifested by defects of reabsorptive and secretory functions in the renal proximal tubule (PT). Previous studies have indicated that, in vivo, Cd causes loss of brush-border membrane (BBM) and impaired function (lower Vmax) of some BBM transporters, whereas in vitro, Cd directly inhibits the activity of several BBM transporters. Our recent studies in Cd-intoxicated rats showed that the lower Vmax of some BBM transporters may be related to the loss of specific proteins from the membrane. In this paper we provide evidence that the loss of BBM proteins in Cd-nephrotoxicity affects not only specific transporters but also other types of membrane proteins, such as ectoenzymes and cell adhesion molecules. Materials and methods: To induce Cd-nephrotoxicity, rats were treated with CdCl2 (2 mg Cd/kg B.W., s.c.) daily for two weeks. Nephrotoxicity was confirmed by the symptoms of reabsorptive defects in the urine and by measuring Cd in the tissue. Specific polyclonal and monoclonal antibodies were used to study the abundance of membrane proteins by indirect immunofluorescence and immunoblotting in cryosections of kidney tissue and isolated renal cortical BBM, respectively. Results: Nephrotoxicity was manifested by phosphaturia, proteinuria, polyuria, and accumulation of Cd in the renal tissue. Immunocytochemical studies in tissue sections from Cd-treated rats showed a dramatic loss of some BBM ecto-proteins, such as carbonic anhydrase IV, dipepdidylpeptidase IV, and cell adhesion molecule CAM-105. These data were supported by decreased density of the corresponding protein bands in immunoblots of isolated BBM. Conclusion: In addition to the loss of reabsorptive surface due to shortening and focal loss of microvilli, the loss of various BBM proteins may contribute to the impairment of PT functions in Cd-nephrotoxicity.

brush-border; cadmium; carbonic anhydrase; cell adhesion molecule; dipeptidyl peptidase; heavy metals; kidney; nephrotoxicity

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