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Citations to this article

Thiol-disulfide effects on hepatic glutathione transport. Studies in cultured rat hepatocytes and perfused livers.
S C Lu, … , J Kuhlenkamp, N Kaplowitz
S C Lu, … , J Kuhlenkamp, N Kaplowitz
Published September 1, 1993
Citation Information: J Clin Invest. 1993;92(3):1188-1197. https://doi.org/10.1172/JCI116689.
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Research Article

Thiol-disulfide effects on hepatic glutathione transport. Studies in cultured rat hepatocytes and perfused livers.

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Abstract

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.

Authors

S C Lu, J L Ge, H Y Huang, J Kuhlenkamp, N Kaplowitz

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Total citations by year

Year: 2021 2014 2011 2010 2009 2005 2003 2002 2000 1999 1998 1997 1996 1995 1994 1981 Total
Citations: 1 1 1 1 1 1 1 2 1 3 1 3 2 1 1 1 22
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Citations to this article (22)

Title and authors Publication Year
Glutathione Participation in the Prevention of Cardiovascular Diseases
D Matuz-Mares, H Riveros-Rosas, MM Vilchis-Landeros, H Vázquez-Meza
Antioxidants 2021
GSH protects against oxidative stress and toxicity in VL-17A cells exposed to high glucose
SM Kumar, K Swaminathan, DL Clemens, A Dey
European Journal of Nutrition 2014
Dealing with stress
N Kaplowitz
Hepatology 2011
Liv.52 attenuate copper induced toxicity by inhibiting glutathione depletion and increased antioxidant enzyme activity in HepG2 cells
S Vidyashankar, PS Patki
Food and Chemical Toxicology 2010
Glutathione in liver diseases and hepatotoxicity
L Yuan, N Kaplowitz
Molecular Aspects of Medicine 2009
Human gastric signet ring carcinoma (KATO-III) cell apoptosis induced by Vitex agnus-castus fruit extract through intracellular oxidative stress
K Ohyama, T Akaike, M Imai, H Toyoda, C Hirobe, T Bessho
The International Journal of Biochemistry & Cell Biology 2005
Signaling Role of Intracellular Iron in NF-κB Activation
S Xiong, H She, H Takeuchi, B Han, JF Engelhardt, CH Barton, E Zandi, C Giulivi, H Tsukamoto
The Journal of biological chemistry 2003
Chronic exposure of HepG2 cells to excess copper results in depletion of glutathione and induction of metallothionein
I Jiménez, P Aracena, ME Letelier, P Navarro, H Speisky
Toxicology in Vitro 2002
The Thiol Sensitivity of Glutathione Transport in Sidedness-Sorted Basolateral Liver Plasma Membrane and in Oatp1-Expressing HeLa Cell Membrane
A Mittur, AW Wolkoff, N Kaplowitz
Molecular pharmacology 2002
Radiation inactivation studies of hepatic sinusoidal reduced glutathione transport system
AV Mittur, N Kaplowitz, ES Kempner, M Ookhtens
Biochimica et Biophysica Acta (BBA) - Biomembranes 2000
Involvement of N-Acetylcysteine-sensitive Pathways in Ricin-induced Apoptotic Cell Death in U937 Cells
T ODA, J IWAOKA, N KOMATSU, T MURAMATSU
Bioscience, Biotechnology, and Biochemistry 1999
Investigation of the transport of intact glutathione in human and rat type II pneumocytes
RJ van Klaveren, PH Hoet, M Demedts, B Nemery
Free Radical Research 1999
Lung glutathione and oxidative stress: implications in cigarette smoke-induced airway disease
I Rahman, W MacNee
American journal of physiology. Lung cellular and molecular physiology 1999
Identification of Glutathione as a Driving Force and Leukotriene C 4 as a Substrate for oatp1, the Hepatic Sinusoidal Organic Solute Transporter
L Li, TK Lee, PJ Meier, N Ballatori
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
T lantomasi, F Favilli, P Marraccini, T Magaldi, P Bruni, MT Vincenzini
Biochimica et Biophysica Acta (BBA) - Biomembranes 1997
Rapid and Specific Efflux of Glutathione before Hepatocyte Injury Induced by Hypoxia
S Khan, PJ O'Brien
Biochemical and Biophysical Research Communications 1997
Role of two recently cloned rat liver GSH transporters in the ubiquitous transport of GSH in mammalian cells
SC Lu, WM Sun, J Yi, M Ookhtens, G Sze, N Kaplowitz
Journal of Clinical Investigation 1996
Review
M Epstein
Renal Failure 1996
Platelet glutathione transport: characteristics and evidence for regulation by intraplatelet thiol status
DJ Sexton, B Mutus
Biochemistry and Cell Biology 1995
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
G Cahill, T Aoki, R Smith
Current Topics in Cellular Regulation 1981

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