Reduction and binding of arsenate and dimethylarsinate by glutathione: a magnetic resonance study

Delnomdedieu, Marielle; Basti, Mufeed M.; Otvos, James D.; Thomas, David J.

doi:10.1016/0009-2797(94)90099-x

Cited by 288 publications

(173 citation statements)

References 28 publications

Supporting

Mentioning

163

Contrasting

Unclassified

Order By: Relevance

“…The monomethyl metabolite of arsenic conjugates with two equivalents of glutathione to form methylarsenic diglutathione (MADG) [27,39]. The dimethyl metabolite of arsenic conjugates with one equivalent of glutathione to form dimethylarsenic glutathione (DMAG) [39,40]. Previous study showed that ATG and MADG, but not DMAG, is transported out of hepatocytes via the MRP2/ cMOAT transporter [27].…”

Section: Discussionmentioning

confidence: 99%

Organic anion transporting polypeptide-C mediates arsenic uptake in HEK-293 cells

Lu¹,

Tamai²,

Nezu³

et al. 2006

J Biomed Sci

View full text Add to dashboard Cite

SummaryArsenic is an established human carcinogen. The role of aquaglyroporins (AQPs) in arsenic disposition was recently identified. In order to examine whether organic anion transporting polypeptide-C (OATP-C) also plays a role in arsenic transport, OATP-C cDNA was transfected into cells of a human embryonic kidney cell line (HEK-293). Transfection increased uptake of the model OATP-C substrate, estradiol-17b-D-glucuronide, by 10-fold. In addition, we measured uptake and cytotoxicity of arsenate, arsenite, monomethylarsonate(MMA V ), and dimethylarsinate (DMA V ). Transfection of OATP-C increased uptake and cytotoxicity of arsenate and arsenite, but not of MMA V or DMA V . Rifampin and taurocholic acid (a substrate of OATP-C) reversed the increased toxicity of arsenate and arsenite seen in OATP-C-transfected cells. The increase in uptake of inorganic arsenic was not as great as that of estradiol-17b-D-glucuronide. Our results suggest that OATP-C can transport inorganic arsenic in a (GSH)-dependent manner. However, this may not be the major pathway for arsenic transport.

show abstract

Section: Discussionmentioning

confidence: 99%

Organic anion transporting polypeptide-C mediates arsenic uptake in HEK-293 cells

Lu¹,

Tamai²,

Nezu³

et al. 2006

J Biomed Sci

View full text Add to dashboard Cite

show abstract

“…Previous work had already provided a link between arsenite and GSH metabolism (36,37). Arsenite and GSH can form an As(SG)3 complex, as detected by NMR (38,39), and this may be the form in which arsenite is excreted. In our HPLC analysis, the main peak of radioactivity comigrated with GSSG, but no GSSG was detected when the medium was directly analyzed by an enzymatic method.…”

Section: Discussionmentioning

confidence: 99%

Role of glutathione in the export of compounds from cells by the multidrug-resistance-associated protein.

Zaman

Lankelma

Tellingen

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

436

298

View full text Add to dashboard Cite

Multidrug-resistance-associated protein [6][7][8] and is able to decrease cellular drug levels against a concentration gradient (4, 6). However, recent work has also indicated interesting differences between MRP and Pgp. Increased cellular MRP levels are associated with increased reduced glutathione (GSH) S-conjugate carrier (GS-X pump) activity in isolated plasma membrane vesicles (9-11). This suggests that MRP is a GS-X pump (12) present in many, if not all, mammalian cells (9-13). These pumps transport substrates containing a large hydrophobic moiety and at least two negative charges (12, 13), as present in drug GSH Sconjugates. Moreover, recent studies indicate that GS-X pumps are also involved in the export of cisplatin (14-16) and arsenite (11). Indeed, some cell lines overexpressing MRP are moderately resistant to arsenite (4, 11). These results link MRP to older experiments in which resistance to anthracyclines was found to correlate with increased levels of cellular GSH, GSH synthesis, or GSH Stransferases (17)(18)(19). This link is supported by the strong decrease in drug resistance in two MDR lung carcinoma cell lines that overexpress MRP by DL-buthionine (S,R)-sulfoximine (BSO) (20)(21)(22), an inhibitor of y-glutamylcysteine synthetase, the enzyme that catalyzes the first step in GSH synthesis (23). The interpretation of these inhibitor experiments is not unambiguous, however. In both cell lines, other resistance mechanisms (e.g., alterations in topoisomerase II) contribute to resistance, and it is not clear whether the GSH depletion in these cells does not result in membrane damagee.g., by lipid peroxidation. Damage of the plasma membrane could increase drug influx and, hence, decrease resistance. To test whether GSH is specifically required for MDR caused by MRP but not by Pgp, we have analyzed the effects of BSO treatment on lung cancer cells transfected with an expression vector containing either MRP cDNA or MDR1 cDNA. MATERIALS AND METHODSCell Lines. S1(MRP) was obtained after transfection of non-small cell lung cancer SW-1573/S1 cells with an expression vector containing MRP cDNA and a neomycin-resistance marker gene (pRc/RSV-MRP), followed by selection with geneticin (G418) (6). Sl(MDR1) was previously named S1(1.1) (24) and was obtained after transfection of S1 cells with the expression vector pJ3fl (25) containing MDR1 cDNA, followed by selection with 10 nM vincristine. GLC4/ADR is a MRP-overexpressing subline of the non-small cell lung cancer cell line GLC4 and was obtained by selection with doxorubicin (20,21).Clonogenic Survival Assay. In six-well dishes, 400 cells per well were seeded and incubated in medium with or without 25 ,uM BSO for 24 hr prior to incubation with increasing concentrations of drug. After 1 hr, drug was removed, the wells were rinsed with phosphate-buffered saline, and drug-free medium without BSO was added. Seven days after the start of the experiment, the percentage of cells that were able to produce a colony of >50 cells was used as a measure of cell sur...

show abstract

“…The presence of thiols such as cysteine or glutathione in the biological matrix may result in reduction of pentavalent arsenicals and formation of complexes [43], possibly unstable [44], which manifests itself as presence of trivalent arsenicals (which, of course, is technically true). This must be taken into account in metabolic studies.…”

Section: Methods Selectivity and Stability Of Standard Solutionsmentioning

confidence: 99%

Oxidation state specific generation of arsines from methylated arsenicals based on l-cysteine treatment in buffered media for speciation analysis by hydride generation-automated cryotrapping-gas chromatography-atomic absorption spectrometry with the multiatomizer

Matoušek

Hernández-Zavala

Svoboda

et al. 2008

Spectrochimica Acta Part B: Atomic Spectroscopy

Self Cite

148

View full text Add to dashboard Cite

An automated system for hydride generation -cryotrapping-gas chromatography -atomic absorption spectrometry with the multiatomizer is described. Arsines are preconcentrated and separated in a Chromosorb filled U-tube. An automated cryotrapping unit, employing nitrogen gas formed upon heating in the detection phase for the displacement of the cooling liquid nitrogen, has been developed. The conditions for separation of arsines in a Chromosorb filled U-tube have been optimized. A complete separation of signals from arsine, methylarsine, dimethylarsine, and trimethylarsine has been achieved within a 60 s reading window. The limits of detection for methylated arsenicals tested were 4 ng l −1 . Selective hydride generation is applied for the oxidation state specific speciation analysis of inorganic and methylated arsenicals. The arsines are generated either exclusively from trivalent or from both tri-and pentavalent inorganic and methylated arsenicals depending on the presence of L-cysteine as a prereductant and/or reaction modifier. A TRIS buffer reaction medium is proposed to overcome narrow optimum concentration range observed for the L-cysteine modified reaction in HCl medium. The system provides uniform peak area sensitivity for all As species. Consequently, the calibration with a single form of As is possible. This method permits a highthroughput speciation analysis of metabolites of inorganic arsenic in relatively complex biological matrices such as cell culture systems without sample pretreatment, thus preserving the distribution of tri-and pentavalent species.

show abstract

Reduction and binding of arsenate and dimethylarsinate by glutathione: a magnetic resonance study

Cited by 288 publications

References 28 publications

Organic anion transporting polypeptide-C mediates arsenic uptake in HEK-293 cells

Organic anion transporting polypeptide-C mediates arsenic uptake in HEK-293 cells

Role of glutathione in the export of compounds from cells by the multidrug-resistance-associated protein.

Oxidation state specific generation of arsines from methylated arsenicals based on l-cysteine treatment in buffered media for speciation analysis by hydride generation-automated cryotrapping-gas chromatography-atomic absorption spectrometry with the multiatomizer

Contact Info

Product

Resources

About