The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Role of glutathione in the export of compounds from cells by the multidrug-resistance-associated protein.
Open accessAbstract
Multidrug-resistance-associated protein (MRP) is a plasma membrane glycoprotein that can confer multidrug resistance (MDR) by lowering intracellular drug concentration. Here we demonstrate that depletion of intracellular glutathione by DL-buthionine (S,R)-sulfoximine results in a complete reversal of resistance to doxorubicin, daunorubicin, vincristine, and VP-16 in lung carcinoma cells transfected with a MRP cDNA expression vector. Glutathione depletion had less effect on MDR in cells transfected with MDR1 cDNA encoding P-glycoprotein and did not increase the passive uptake of daunorubicin by cells, indicating that the decrease of MRP-mediated MDR was not due to nonspecific membrane damage. Glutathione depletion resulted in a decreased efflux of daunorubicin from MRP-transfected cells, but not from MDR1-transfected cells, suggesting that glutathione is specifically required for the export of drugs from cells by MRP. We also show that MRP increases the export of glutathione from the cell and this increased export is further elevated in the presence of arsenite. Our results support the hypothesis that MRP functions as a glutathione S-conjugate carrier.
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Citations
Cites
Overexpression of a Transporter Gene in a Multidrug-Resistant Human Lung Cancer Cell Line
Cole, S. P. C., Bhardwaj, G., Gerlach, J. H., Mackie, J. E., Grant, C. E., Almquist, K. C., Stewart, A. J., Kurz, E. U., Duncan, A. M. V., & Deeley, R. G. (1992) · Science · doi:10.1126/science.1360704 · Cited by 3,037
Cited by
Targeting multidrug resistance in cancer
Szakács, G., Paterson, J. K., Ludwig, J. A., Booth-Genthe, C., & Gottesman, M. M. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd1984 · Cited by 3,609
A family of drug transporters: the multidrug resistance-associated proteins
Borst, P., Evers, R., Kool, M., & Wijnholds, J. (2000) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/92.16.1295 · Cited by 1,751
Self-citationGlutathione in Cancer Biology and Therapy
Estrela, J. M., Ortega, A., & Obrador, E. (2006) · Critical Reviews in Clinical Laboratory Sciences · doi:10.1080/10408360500523878 · Cited by 1,041
Role of Glutathione in Cancer: From Mechanisms to Therapies
Kennedy, L., Sandhu, J. K., Harper, M.-E., & Cuperlovic-Culf, M. (2020) · Biomolecules · doi:10.3390/biom10101429 · Cited by 880
Deeley, R. G., Westlake, C., & Cole, S. P. C. (2006) · Physiological Reviews · doi:10.1152/physrev.00035.2005 · Cited by 761
Toxicological relevance of the multidrug resistance protein 1, MRP1 (ABCC1) and related transporters
Leslie, E. (2001) · Toxicology · doi:10.1016/s0300-483x(01)00454-1 · Cited by 376
Hanssen, K. M., Haber, M., & Fletcher, J. I. (2021) · Drug Resistance Updates · doi:10.1016/j.drup.2021.100795 · Cited by 102
Metadata
- Authors
- Zaman, G. J., Lankelma, J., van Tellingen, O., Beijnen, J., Dekker, H., Paulusma, C., Oude Elferink, R. P., Baas, F., & Borst, P.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1995-08-15
- Volume
- 92
- Issue
- 17
- Pages
- 7690-7694
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2012841076
- Cited by
- 498
- References
- 1
- FWCI
- 16.06
- Type
- journal article
- Language
- en
- Open access
- green
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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