Biochemical and Unctional Characteristics of Cultured Renal Epithelial Cells from Uninephrectomized Rats:Factors Influencing Nephrotoxicity

摘要

Primary cultures of renal proximal (PT) and distal tubular (DT) cells from control and uninephrectomized (NPX) Sprague-Daw-~y rats were established to characterize factors that are re-~orisible for the altered susceptibility to nephrotoxicants that occurs after compensatory renal cellular hypertrophy. Cells ~re grown in serum-free, hormonally defined medium and ~arneters were measured on days 1, 3, and 5 of primary aiture. PT and DT cells from control and NPX rats appeared to uu~ritain epithelial characteristics in culture, as shown by cyto-~ratin staining, morphology, protein and DNA content, and enzyme activities. Activities of several glutathione-dependent enzymes, including -glutamyltransferase, glutathione S-trans-~rase, glutathione peroxidase, and y-glutamylcysteine syn-~ase, were significantly greater in PT cells from NPX rats than in PT cells from control rats when factored by protein content. Rates of a-methylglucose uptake across the basolat-eral and brush-border membranes and sodium-dependent up-take of glutathione across the basolateral membrane were 2- to 3-fold higher in PT cells from NPX rats than in PT cells from control rats. These results are consistent with the hypertro-phied phenotype being maintained in primary cultures of PT cells from NPX rats. The marked alterations in transport may play central roles in the delivery of nephrotoxicants to the target cell, and thus, increases the probability of chemically induced injury or death. These findings also suggest that these cell cultures may be useful for the study of biochemical processes associated with compensatory renal cellular hypertrophy.