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KMID : 0811719970010010035
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Korean Journal of Physiology & Pharmacology
1997 Volume.1 No. 1 p.35 ~ p.43
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Effect of Cisplatin on Sodium-Dependent Hexose Transport in LLC-PK1 Renal Epithelial Cells
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Suk Kyu Lee
Jee Yeun Kim/Tai Hyun Yu/Kyoung Ryong Kim/Kwang Hyuk Kim/Yang Saeng Park
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Abstract
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Cis-dichlorodiammine platinμMII (Cisplatin), an effective chemotherapeutic agent, induces acute renal failure by unknown mechanisms. To investigate direct toxic effects of cisplatin on the renal proximal tubular transport system, LLC-PK1 cell line was selected as a cell model and the sugar transport activity was evaluated during a course of cisplatin treatment. Cells grown to confluence were treated with cisplatin for 60 min, washed, and then incubated for up to 5 days. At appropriate intervals, cells were tested for sugar transport activity using α?methyl?D?[14C]glucopyranoside (AMG) as a model substrate. In cells treated with 100 μM cisplatin, the AMG uptake was progressively impaired after 3 days. The viability of cells was not substantially changed with cisplatin of less than 100 μM, but it decreased markedly with 150 and 200 μM. In cisplatin-treated cells, the Na+ -dependent AMG uptake was drastically inhibited with no change in the Na+ -independent uptake. Kinetic analysis indicated that Vmax was suppressed, but Km was not altered. The Na+ -dependent phlorizin binding was also decreased in cisplatin-treated cells. However, the AMG efflux from preloaded cells was not apparently retarded by cisplatin treatment. These data indicate that the cisplatin treatment impairs Na+ -hexose cotransporters in LLC-PK1 cells and suggest strongly that defects in transporter function at the luminal plasma membrane of the proximal tubular cells constitute an important pathogenic mechanism of cisplatin nephrotoxicity.
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KEYWORD
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Cisplatin, LLC-PK1 cell, Na-hexose cotransport, Phlorizin,
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