Effect of cisplatin on sodium-dependent hexose transport in LLC-PK-1 renal epithelial cells.
- Author:
Suk Kyu LEE
1
;
Jee Yeun KIM
;
Tai Hyun YU
;
Kyoung Ryong KIM
;
Kwang Hyuk KIM
;
Yang Saeng PARK
Author Information
1. Departments of Otolaryngology, Physiology, and Microbiology Kosin Medical, Pusan 602-030 South Korea.
- Publication Type:Original Article
- Keywords:
cisplatin;
LLC-PK1 cell;
Nhexose cotransport;
phlorizin
- MeSH:
Acute Kidney Injury;
Animals;
Cell Line;
Cell Membrane;
Cisplatin*;
Epithelial Cells*;
LLC-PK1 Cells;
Phenobarbital;
Phlorhizin;
Platinum;
Swine
- From:The Korean Journal of Physiology and Pharmacology
1997;1(1):35-43
- CountryRepublic of Korea
- Language:English
-
Abstract:
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-1 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 alpha-methyl-D-(14C)glucopyranoside (AMG) as a model substrate. In cells treated with 100 micrometer cisplatin, the AMG uptake was progressively impaired after 3 days. The viability of cells was not substantially changed with cisplatin of less than 100 micrometer, but it decreased markedly with 150 and 200 micrometer. 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-PK-1 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.
