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KMID : 0370219960400060705
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Yakhak Hoeji
1996 Volume.40 No. 6 p.705 ~ p.712
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Mechanism of Inhibition of alpha-Methylglucose Uptake by Cisplatin in LLC-PK1
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서경원/Seo KW
김효정/정세영/Kim HJ/Choung SY
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Abstract
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We have previously shown that determination of glucose uptake using alpha-methylglucose(alpha-MG) is very sensitive and rapid parameter for the assessment of loss of cellular function in renal cell line(LLC-PK1). The present study was designed to elucidate the mechanism of inhibition of alpha-MG uptake and the intracellular site of toxic action of cisplatin(CIS). LLC-PK1 cells were exposed to various concentrations(5mcM-lOOmcM) of CIS for 5 hrs or 24 hrs and alpha-MG uptake was determined. Mitochondrial function was evaluated by measuring intracellular ATP content and MTT reduction. The activities of marker enzymes for the basolateral membrane(Na+-K+ ATPase) and brush border membrane (alkaline phosphatase: ALP) were also measured. CIS treatment significantly inhibited the alpha-MG uptake in a time- and dose-dependent manner above 25mcM for 5 hrs. Intracellular ATP content and MTT reduction were affected by 24 hr-treatment of 50mcM CIS. The activities of Na+-K+ ATPase and ALP were significantly decreased at 10mcM and 5mcM of CIS for 24 hrs, respectively. The incubation with CIS for 5 hrs had no effects on the intracellular ATP content, MTT reduction and the activities of marker enzymes up to 100mcM. These results partly indicate that inhibition of alpha-MG uptake by CIS may not be attributed to the disturbance of mitochondrial function or inhibition of the activity of Na+-K+ ATPase and can be resulted from direct effect of CIS on the Na+/glucose cotransporter in brush border membrane. This study shows that additional mechanistic information, indicating the intracellular site of nephrotoxic action, can be gained by coupling the alpha-MG uptake and ATP content or the activity of Na+-K+ ATPase.
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