Erythrocyte membrane transport of glutathione conjugates and oxidized glutathione in the dubin-johnson syndrome and in rats with hereditary hyperbilirubinemia

Authors

  • Philip Board,

    1. Molecular Genetics Group, John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia
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  • Toshirou Nishida,

    1. Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 0211
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  • Zenaida Gatmaitan,

    1. Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 0211
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  • Mingxin Che,

    1. Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 0211
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  • Irwin M. Arias M.D.

    Corresponding author
    1. Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 0211
    2. Molecular Genetics Group, John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia
    • Department of Physiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111
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Abstract

The Dubin-Johnson syndrome is manifested by conjugated hyperbilirubinemia and pigment accumulation in hepatocellular lysosomes. The TR- rat model is a phenotypic model of the Dubin-Johnson syndrome and is characterized by defective ATP-dependent transport of a group of nonbile acid organic anions, including glutathione-S-conjugates and oxidized glutathione, across the bile canaliculus. Similar ATP-dependent transport mechanisms have been described in erythrocytes. Intact erythrocytes and inverted erythrocyte membrane vesicles from Dubin-Johnson patients, TR-rats and appropriate controls were studied with regard to ATP-dependent transport of dinitrophenyl glutathione and oxidized glutathione. No significant differences were observed, indicating that the erythrocyte and canalicular ATP-dependent transporters for these substrates are functionally and potentially genetically distinct. (Hepatology 1992;15:722–725).

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