Effect of cisplatin on sodium-dependent hexose transport in LLC-PK-1 renal epithelial cells
The Korean Journal of Physiology and Pharmacology
;
: 35-43, 1997.
Article
in English
| WPRIM
| ID: wpr-727809
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Phenobarbital
/
Phlorhizin
/
Platinum
/
Swine
/
Cell Line
/
Cell Membrane
/
Cisplatin
/
LLC-PK1 Cells
/
Epithelial Cells
/
Acute Kidney Injury
Limits:
Animals
Language:
English
Journal:
The Korean Journal of Physiology and Pharmacology
Year:
1997
Type:
Article
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