Effect of Cisplatin on Sodium-Dependent Hexose Transport in LLC-PK<SUB>1</SUB> Renal Epithelial Cells
Effect of Cisplatin on Sodium-Dependent Hexose Transport in LLC-PK<SUB>1</SUB> Renal Epithelial Cells
- Suk Kyu Lee Jee Yeun Kim Tai Hyun Yu Kyoung Ryong Kim Kwang Hyuk Kim Yang Saeng Park
- 대한생리학회-대한약리학회
- The Korean Journal of Physiology & Pharmacology
- 제1권 제1호
- 등재여부 : KCI등재
- 1997.01
- 35 - 43 (9 pages)
<P> Cis-dichlorodiammine platinum II (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-PK<SUB>1 </SUB>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-[<SUP>14</SUP>C]glucopyranoside (AMG) as a model substrate. In cells treated with 100 ㄍM cisplatin, the AMG uptake was progressively impaired after 3 days. The viability of cells was not substantially changed with cisplatin of less than 100 ㄍM, but it decreased markedly with 150 and 200 ㄍM. In cisplatin-treated cells, the Na<SUP>+</SUP>-dependent AMG uptake was drastically inhibited with no change in the Na<SUP>+</SUP>-independent uptake. Kinetic analysis indicated that Vmax was suppressed, but Km was not altered. The Na<SUP>+</SUP>-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<SUP>+</SUP>-hexose cotransporters in LLC-PK<SUB>1</SUB> 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.