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• W2316291015 abstract "The established renal cell line LLC-PK1 was used as a model to investigate the mechanism underlying kidney malfunction observed in cystinosis patients. In this disease lysosomal accumulation of cystine impairs kidney function, and glycosuria is an early clinical manifestation. The linkage between lysosomal accumulation of cystine and impairment of kidney function is still unclear, and no animal model is available. In an attempt to gain a better insight into this relationship, we studied the effects of lysosomal loading with cystine on the survival and functions of normal noncystinotic renal epithelial cells (LLC-PK1), nonrenal fibroblasts (NIH-3T3), and cystinotic fibroblasts (GM2837). Incubation of the cells with cystine dimethylester (CDME) resulted in time- and dose-dependent accumulation of cystine, with 80% of the cystine in the lysosomal fraction. The lysosomal concentration of cystine increased in the three cell lines after 3 hours of incubation and declined significantly after 48 hours in the normal, but not cystinotic, cells. The accumulation of cystine in the lysosomes caused dose- and time-dependent cell mortality, assessed by measuring the activity of the cytosolic enzyme, lactic dehydrogenase, in the medium. Survival of fibroblasts and renal cells was similar in all three cell lines. The concentrating capacity (the ratio fo the intra- and extracellular concentrations) of the nonmetabolized sugar analog, alpha methyl glucoside (AMG), was used to assess the function of the kidney cells. The sugar concentrating capacity of LLC-PK1 cells was reduced after incubation with CDME in a dose- and time-dependent manner. Since there was no change in sugar efflux between the untreated and treated cells, we conclude that an impairment of the uptake of AMG is responsible for the reduction in the sugar-concentrating capacity in LLC-PK1 cells. In the absence of a genetically impaired animal model, LLC-PK1 cells treated with CDME can be used to investigate the cellular mechanisms responsible for the impairment of kidney function in cystinotic patients." @default.
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• W2316291015 date "1990-01-01" @default.
• W2316291015 modified "2023-10-14" @default.
• W2316291015 title "RENAL CELLS IN CULTURE AS A MODEL FOR CYSTINOSIS" @default.
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• W2316291015 doi "https://doi.org/10.1515/jbcpp.1990.1.1-4.357" @default.
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