Inhibition of the proton-coupled folate transporter (PCFT-SLC46A1) by bicarbonate and other anions

Molecular Pharmacology

Volumn 84, Issue 1, 2013, Pages 95-103

  Zhao, Rongbao ^a,b,c   Visentin, Michele ^a   Suadicani, Sylvia O ^c   Goldman, I David ^a,b  

^a Departments of Molecular Pharmacology   (United States)

^b Departments of Medicine and Pediatrics   (United States)

^c ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 (2 HYDROXYETHYL) 1 PIPERAZINEETHANESULFONIC ACID; ACETIC ACID; ANION; BICARBONATE; BISULFITE; BUFFER; CITRIC ACID; GLYCINE; NITRATE; NITRITE; PHOSPHATE; PROTON; PROTON COUPLED FOLATE TRANSPORTER; PYRUVIC ACID; REDUCED FOLATE CARRIER; SODIUM CHLORIDE; SULFATE;

ACIDITY; ARTICLE; CELL PH; CONTROLLED STUDY; DIFFUSION; FEMALE; HUMAN; HUMAN CELL; INHIBITION KINETICS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTON TRANSPORT;

ACETIC ACID; ANIONS; BICARBONATES; CELL LINE, TUMOR; CITRIC ACID; FOLIC ACID TRANSPORTERS; GLYCINE; HELA CELLS; HUMANS; HYDROGEN-ION CONCENTRATION; KINETICS; MEMBRANE TRANSPORT PROTEINS; NITRATES; PROTON-COUPLED FOLATE TRANSPORTER; PROTONS; PYRUVIC ACID; SULFITES;

EID: 84879107962     PISSN: 0026895X     EISSN: 15210111     Source Type: Journal    
DOI: 10.1124/mol.113.085605     Document Type: Article

References (30)

1. Chow CK and Hong CB (2002) Dietary vitamin E and selenium and toxicity of nitrite and nitrate. Toxicology 180:195-207.
2. Diop-Bove N, Kronn D, and Goldman ID (2011) Hereditary folate malabsorption, in GeneReviews [Internet] (Pagon RA, Bird TD, Dolan CR and Stephens K eds), University of Washington, Seattle, Seattle, WA.
3. Diop-Bove NK, Wu J, Zhao R, Locker J, and Goldman ID (2009) Hypermethylation of the human proton-coupled folate transporter (SLC46A1) minimal transcriptional regulatory region in an antifolate-resistant HeLa cell line. Mol Cancer Ther 8: 2424-2431.
4. Helmlinger G, Yuan F, Dellian M, and Jain RK (1997) Interstitial pH and pO2 gradients in solid tumors in vivo: high-resolution measurements reveal a lack of correlation. Nat Med 3:177-182.
5. Henderson GB and Zevely EM (1983) Structural requirements for anion substrates of the methotrexate transport system in L1210 cells. Arch Biochem Biophys 221: 438-446.
6. Inoue K, Nakai Y, Ueda S, Kamigaso S, Ohta KY, Hatakeyama M, Hayashi Y, Otagiri M, and Yuasa H (2008) Functional characterization of PCFT/HCP1 as the molecular entity of the carrier-mediated intestinal folate transport system in the rat model. Am J Physiol Gastrointest Liver Physiol 294:G660-G668
7. Kugel Desmoulin S, Wang L, Hales E, Polin L, White K, Kushner J, Stout M, Hou Z, Cherian C, and Gangjee A et al. (2011) Therapeutic targeting of a novel 6-substituted pyrrolo [2,3-d]pyrimidine thienoyl antifolate to human solid tumors based on selective uptake by the proton-coupled folate transporter. Mol Pharmacol 80:1096-1107.
8. Kugel Desmoulin S, Wang Y, Wu J, Stout M, Hou Z, Fulterer A, Chang MH, Romero MF, Cherian C, and Gangjee A et al. (2010) Targeting the proton-coupled folate transporter for selective delivery of 6-substituted pyrrolo[2,3-d] pyrimidine antifolate inhibitors of de novo purine biosynthesis in the chemotherapy of solid tumors. Mol Pharmacol 78:577-587.
9. Nakai Y, Inoue K, Abe N, Hatakeyama M, Ohta KY, Otagiri M, Hayashi Y, and Yuasa H (2007) Functional characterization of human proton-coupled folate transporter/heme carrier protein 1 heterologously expressed in mammalian cells as a folate transporter. J Pharmacol Exp Ther 322:469-476.
10. Parker JC (1969) Influence of 2,3-diphosphoglycerate metabolism on sodiumpotassium permeability in human red blood cells: studies with bisulfite and other redox agents. J Clin Invest 48:117-125.
11. Qiu A, Jansen M, Sakaris A, Min SH, Chattopadhyay S, Tsai E, Sandoval C, Zhao R, Akabas MH, and Goldman ID (2006) Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption. Cell 127: 917-928
12. Raghunand N, Altbach MI, van Sluis R, Baggett B, Taylor CW, Bhujwalla ZM, and Gillies RJ (1999) Plasmalemmal pH-gradients in drug-sensitive and drugresistant MCF-7 human breast carcinoma xenografts measured by 31P magnetic resonance spectroscopy. Biochem Pharmacol 57:309-312.
13. Reed LS and Archer MC (1979) Action of sodium nitrite on folic acid and tetrahydrofolic acid. J Agric Food Chem 27:995-999.
14. Rosowsky A, Wright JE, Vaidya CM, Bader H, Forsch RA, Mota CE, Pardo J, Chen CS, and Chen YN (1998) Synthesis and potent antifolate activity and cytotoxicity of B-ring deaza analogues of the nonpolyglutamatable dihydrofolate reductase inhibitor Nalpha-(4-Amino-4-deoxypteroyl)-Ndelta-hemiphthaloyl-L- ornithine (PT523). J Med Chem 41:5310-5319.
15. Umapathy NS, Gnana-Prakasam JP, Martin PM, Mysona B, Dun Y, Smith SB, Ganapathy V, and Prasad PD (2007) Cloning and functional characterization of the proton-coupled electrogenic folate transporter and analysis of its expression in retinal cell types. Invest Ophthalmol Vis Sci 48:5299-5305.
16. Unal ES, Zhao R, Chang MH, Fiser A, Romero MF, and Goldman ID (2009a) The functional roles of the His247 and His281 residues in folate and proton translocation mediated by the human proton-coupled folate transporter SLC46A1. J Biol Chem 284:17846-17857.
17. Unal ES, Zhao R, and Goldman ID (2009b) Role of the glutamate 185 residue in proton translocation mediated by the proton-coupled folate transporter SLC46A1. Am J Physiol Cell Physiol 297:C66-C74.
18. Visentin M, Zhao R, and Goldman ID (2012) Augmentation of reduced folate carriermediated folate/antifolate transportg through an antiport mechanism with 5-Aminoimidazole-4-carboxamide riboside monophosphate. Mol Pharmacol 82: 209-216.
19. Vonderschmitt DJ, Vitols KS, Huennekens FM, and Scrimgeour KG (1967) Addition of bisulfite to folate and dihydrofolate. Arch Biochem Biophys 122:488-493.
20. Wang L, Kugel Desmoulin S, Cherian C, Polin L, White K, Kushner J, Fulterer A, Chang MH, Mitchell-Ryan S, and Stout M et al. (2011) Synthesis, biological, and antitumor activity of a highly potent 6-substituted pyrrolo[2,3-d]pyrimidine thienoyl antifolate inhibitor with proton-coupled folate transporter and folate receptor selectivity over the reduced folate carrier that inhibits b-glycinamide ribonucleotide formyltransferase. J Med Chem 54:7150-7164.
21. Wang Y, Zhao R, and Goldman ID (2004) Characterization of a folate transporter in HeLa cells with a low pH optimum and high affinity for pemetrexed distinct from the reduced folate carrier. Clin Cancer Res 10:6256-6264.
22. Wike-Hooley JL, Haveman J, and Reinhold HS (1984) The relevance of tumour pH to the treatment of malignant disease. Radiother Oncol 2:343-366.
23. Yang C-H, Sirotnak FM, and Dembo M (1984) Interaction between anions and the reduced folate/methotrexate transport system in L1210 cell plasma membrane vesicles: directional symmetry and anion specificity for differential mobility of loaded and unloaded carrier. J Membr Biol 79:285-292.
24. Zhao R, Gao F, Wang Y, Diaz GA, Gelb BD, and Goldman ID (2001) Impact of the reduced folate carrier on the accumulation of active thiamin metabolites in murine leukemia cells. J Biol Chem 276:1114-1118
25. Zhao R, Diop-Bove N, Visentin M, and Goldman ID (2011a) Mechanisms of membrane transport of folates into cells and across epithelia. Annu Rev Nutr 31: 177-201.
26. Zhao R, Gao F, Hanscom M, and Goldman ID (2004a) A prominent low-pH methotrexate transport activity in human solid tumors: contribution to the preservation of methotrexate pharmacologic activity in HeLa cells lacking the reduced folate carrier. Clin Cancer Res 10:718-727.
27. Zhao R, Hanscom M, Chattopadhyay S, and Goldman ID (2004b) Selective preservation of pemetrexed pharmacological activity in HeLa cells lacking the reduced folate carrier: association with the presence of a secondary transport pathway. Cancer Res 64:3313-3319.
28. Zhao R, Matherly LH, and Goldman ID (2009) Membrane transporters and folate homeostasis: intestinal absorption and transport into systemic compartments and tissues. Expert Rev Mol Med 11:e4.
29. Zhao R, Qiu A, Tsai E, Jansen M, Akabas MH, and Goldman ID (2008) The protoncoupled folate transporter: impact on pemetrexed transport and on antifolates activities compared with the reduced folate carrier. Mol Pharmacol 74:854-862.
30. Zhao R, Shin DS, Diop-Bove N, Ovits CG, and Goldman ID (2011b) Random mutagenesis of the proton-coupled folate transporter (SLC46A1), clustering of mutations, and the bases for associated losses of function. J Biol Chem 286:24150-24158