시스플라틴에 의한 LLC-PK1의 알파-메틸글루코스 흡수 감소 기전

• 영문명: Mechanism of Inhibition of alpha-Methylglucose Uptake by Cisplatin in LLC-PK1
• 발행기관: 대한약학회
• 저자명: 서경원(Kyung Won Seo) 김효정(Hyo Jung Kim) 정세영(Se Young Choung)
• 간행물 정보: 『약학회지』제40권 제6호 (1996년), 705~712쪽, 전체 8쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 1996.12.31

영문 초록

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.

키워드

Cisplatin LLOPKi α-Methylglucose uptake.