Glutathione-dependent interaction of heavy metal compounds with multidrug resistance proteins MRP1 and MRP2

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• 作者：Heleen M. Wortelboer ; Michiel G.J. Balvers ; Mustafa Usta ; Peter J. van Bladeren ; Nicole H.P. Cnubben
• 关键词：MRP1 ; MRP2 ; Cisplatin ; Arsenic trioxide ; Mercury chloride ; Glutathione
• 刊名：Environmental Toxicology and Pharmacology
• 出版年：2008
• 期刊代码：13_13826689
• 类别：pha
• 出版时间：July 2008
• 卷：26
• 期：1
• 页码：102-108
• 文件大小：405 K

摘要

The interactions of three heavy metal-containing compounds, cisplatin (CDDP), arsenic trioxide (As₂O₃), and mercury dichloride (HgCl₂), with the multidrug resistance transporters MRP1 and MRP2 and the involvement of glutathione (GSH)-related processes herein were investigated. In Madin–Darby canine kidney cells stably expressing MRP1 or MRP2, viability, GSH content, calcein efflux and polarized GSH efflux were measured as a function of exposure to CDDP, As₂O₃ and HgCl₂. In isolated Sf9-MRP1 and Sf9-MRP2 membrane vesicles, the interaction with MRP-associated ATPase activity was measured. In the latter model system adduct formation with GSH is not an issue.