In cultured rat hepatocytes, cystine led to an inhibition of GSH efflux by lowering the Vmax by approximately 35% without affecting the Km. The cystine-mediated inhibition of GSH efflux was rapid in onset (< 1 h), with near maximum effect at 0.1 mM. Inhibition was still observed when cystine uptake was prevented. Cystine and sulfobromophthalein-GSH, a selective inhibitor of sinusoidal transport of GSH, did not exhibit additive inhibitory effects on GSH efflux. Depletion of ATP or membrane depolarization after cystine treatment were excluded as potential mechanisms. DTT not only reversed the cystine-mediated inhibition of GSH efflux, it stimulated GSH efflux up to 400-500%. The DTT effect was immediate in onset, reaching maximum after 30 min, and was partially reversed by cystine, suggesting that the two share a common site(s) of action. DTT treatment did not alter cellular ATP levels or change the membrane potential. In cultured hepatocytes, DTT treatment increased the Vmax of GSH efflux by approximately 500% without affecting the Km. Inhibition of microtubular function and vesicular acidification did not affect basal or DTT stimulated efflux. Both cystine and DTT effects on sinusoidal GSH efflux were confirmed in perfused livers. In summary, the capacity of the sinusoidal GSH transporter is markedly influenced by thiol-disulfide status.
S C Lu, J L Ge, H Y Huang, J Kuhlenkamp, N Kaplowitz
Title and authors | Publication | Year |
---|---|---|
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RJ van Klaveren, PH Hoet, M Demedts, B Nemery |
Free Radical Research | 1999 |
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The Journal of biological chemistry | 1998 |
Role of cellular thiol status in tocopheryl hemisuccinate cytoprotection against ethyl methanesulfonate-induced toxicity
M Fariss |
Biochemical Pharmacology | 1997 |
Glutathione transport system in human small intestine epithelial cells
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Review
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Renal Failure | 1996 |
Platelet glutathione transport: characteristics and evidence for regulation by intraplatelet thiol status
DJ Sexton, B Mutus |
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Cocaine-induced liver injury in mice elicits specific changes in DNA ploidy and induces programmed death of hepatocytes
M Cascales, A Alvarez, P Gascó, L Fernández-Simón, N Sanz, L Boscá |
Hepatology | 1994 |
Current Topics in Cellular Regulation
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Current Topics in Cellular Regulation | 1981 |