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Characterization of As(GS)3 and [(GS)2AsSe]‐ transport by the human multidrug resistance protein 2 (MRP2/ABCC2)
Author(s) -
Carew Michael Wayne,
Leslie Elaine MacKay
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.747.1
Subject(s) - multidrug resistance associated protein 2 , glutathione , chemistry , efflux , detoxification (alternative medicine) , excretion , biochemistry , enzyme , atp binding cassette transporter , transporter , medicine , gene , alternative medicine , pathology
Arsenic (As) is a human carcinogen and toxicant, despite this, the key pathways in As metabolism and excretion are not fully understood. Multidrug resistance protein 2 (MRP2/ABCC2) is expressed at the canalicular surface of hepatocytes and can transport glutathione (GSH or GS‐) conjugates, including As(GS) 3 . Studies show an increased detoxification of As when administered with the micronutrient selenium (Se). One proposed mechanism for this is through the formation of [(GS) 2 AsSe] − , which has been isolated from rabbit bile. The purpose of the current study was to investigate the ability of MRP2 to transport As(GS) 3 and [(GS) 2 AsSe] − . Transport activity was measured using membrane vesicles prepared from MRP2 transfected HEK293 cells. As(GS) 3 (0.1 μM) transport by MRP2 was maximal at 5 min (7.7 pmol mg −1 ). The apparent K m and V max of As(GS) 3 for MRP2 were 4.2 ± 0.9 μM and 134 ± 12 pmol mg −1 min −1 , respectively. Transport of [(GS) 2 AsSe] − (0.1 and 1 μM) showed an ~ 3‐fold increase over As(GS) 3 . These data support a role for MRP2 in transporting [(GS) 2 AsSe] − , potentially contributing to As detoxification. Funding was provided by the Alberta Cancer Board, AHFMR and CIHR.