Mercury induces multidrug resistance-associated protein gene through p38 mitogen-activated protein kinase
Mercury induces multidrug resistance-associated protein gene through p38 mitogen-activated protein kinase
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DOI：
10.1016/j.toxlet.2004.09.007
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发表时间：
2005-01-15
影响因子：
3.5
通讯作者：
Choi, CH
中科院分区：
文献类型：
--
作者：
Kim, SH;Bark, H;Choi, CH
The multidrug resistance-associated protein (MRP1) belongs to a drug efflux membrane pump that confers multidrug resistance to the cells. The MRP1 mediates the cellular efflux of various xenobiotics including heavy metals and mediates cellular resistance to heavy metals. Mercury is a well-known health hazard and an environmental contaminant. Recently, information about the uptake of the heavy metals such as mercury has been suggested. However, little is known regarding molecular mechanisms of exporting mercury. This study was designed to determine if mercury could be extruded by MRP1 in acute myeloid leukemia cells (AML-2). The MRP-1-overexpressing AML-2/DX 100 cells showed a higher resistance to mercury than AML-2/WT. Probenecid, which is a specific MRP1 inhibitor, decreased the resistance to mercury. Exposing the AML-2 cells to mercury-induced MRP1 gene expression and production without altering the MRPI activity. Mercury activated p38 mitogen-activated protein kinase (MAPK) and SB 203580, a specific p38 MAPK inhibitor, blocked the mercury-induced MRP1 production. These results suggest that MRPI can control mercury and p38 MAPK mediates the mercury-induced MRP1 gene expression. (C) 2004 Elsevier Ireland Ltd. All rights reserved.
