Erythrocyte membrane transport of glutathione conjugates and oxidized glutathione in the Dubin-Johnson syndrome and in rats with hereditary hyperbilirubinemia.
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.
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Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111.
Nishida
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Gatmaitan
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Arias
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D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004910:Erythrocyte Membrane / Q000378:metabolism*; D005260:Female; D005978:Glutathione / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism*; D019803:Glutathione Disulfide; D006801:Humans; D006933:Hyperbilirubinemia, Hereditary / Q000097:blood*; D007566:Jaundice, Chronic Idiopathic / Q000097:blood*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013379:Substrate Specificity
C030190:S-(2,4-dinitrophenyl)glutathione; D000255:Adenosine Triphosphate; D005978:Glutathione; D019803:Glutathione Disulfide