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- W3175987986 abstract "Background and Aim Genetic defects in the bile salt export pump (ABCB11) gene lead to fatal Type 2 progressive familial intrahepatic cholestasis (PFIC2). However, Abcb11 knockout (KO) mice exhibit only mild cholestasis and secrete large amounts of unusual tetrahydroxyl bile salts into bile (PNAS 98:2011). The formation of hydrophilic bile salts is postulated to detoxify the hydrophobic bile salts and prevent a severe cholestatic phenotype in the KO mice. An unidentified alternative canalicular non-Abcb11-mediated transport system is proposed to efflux these tetrahydroxyl bile salts. Furthermore, 6a-OH-TC is present in human amniotic fluid, neonatal urine and urine of cholestatic patients. Here we investigate human MRP2 as a possible alternative transporter for 6a-OH-TC. Methods Tauro-Δ22-3a, 6a, 7a, 12a -tetrahydroxy-5 β-cholan-24-oic acid was synthesized, reductively tritiated, and purified by TLC and HPLC (98% purity). Human MRP2 was expressed in Sf9 insect cells and the kinetic parameters (Km, Vmax, Hill coefficient [HC]) of ATP dependant transport of 3H-6a-OH-TC determined in Sf9 plasma membrane vesicles. Results Saturation kinetics studies (6a-OH-TC 0.1-1mM) yielded uptake that fit best to the Hill equation with Vmax = 509 pmol/mg/min; Km = 128 µM; Hill coefficient = 1.6. Conclusion 6α-OH-TC is a substrate of MRP2 with evidence of positive cooperativity. (HD 58299)" @default.
- W3175987986 created "2021-07-05" @default.
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- W3175987986 date "2009-04-01" @default.
- W3175987986 modified "2023-09-23" @default.
- W3175987986 title "Human Multidrug Resistance Protein 2 (MRP2/ABCC2) transports 3α, 6α, 7α, 12α‐(OH) 4 ‐5β‐cholyl taurine (6α‐OH‐TC)" @default.
- W3175987986 doi "https://doi.org/10.1096/fasebj.23.1_supplement.747.2" @default.
- W3175987986 hasPublicationYear "2009" @default.
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