QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Park, J. B. Articles by Levine, M. Search for Related Content PubMed PubMed Citation Articles by Park, J. B. Articles by Levine, M.

---

Article

Intracellular Accumulation of Ascorbic Acid Is Inhibited by Flavonoids via Blocking of Dehydroascorbic Acid and Ascorbic Acid Uptakes in HL-60, U937 and Jurkat Cells

Jae B. Park^*1 and Mark Levine

^* Phytonutrients Laboratory, BHNRC, ARS, U.S. Department of Agriculture, Beltsville 20705 Molecular and Clinical Nutrition section, Digestive Diseases Branch, NIDDK, National Institutes of Health, Bethesda 20892, MD

¹To whom correspondence should be addressed.

In HL-60, U937 and Jurkat cells, the intracellular accumulation of ascorbic acid occurred via uptakes of both dehydroascorbic acid (an oxidized metabolite of ascorbic acid) and ascorbic acid (vitamin C). Dehydroascorbic acid and ascorbic acid were transported into cells by sodium-independent glucose transporters (GLUT 1 and GLUT 3) and sodium-dependent ascorbic acid transporters, respectively. Flavonoids inhibited the intracellular accumulation of ascorbic acid by blocking dehydroascorbic acid and ascorbic acid uptakes in the transformed cells. At flavonoid concentrations of 10–70 µmol/L, ~50% of dehydroascorbic acid uptake was inhibited in the cells. In Jurkat cells, two potent flavonoids (myricetin and quercetin) competitively inhibited dehydroascorbic acid uptake, and K_i values were ~14 and 15 µmol/L, respectively. Because GLUT 1 and GLUT 3 transport dehydroascorbic acid, the inhibition of dehydroascorbic acid uptake by flavonoids was investigated by using Chinese hamster ovary cells overexpressing rat GLUT 1 or human GLUT 3. Myricetin at concentrations of 22 and 18 µmol/L, respectively, inhibited half of dehydroascorbic acid uptake in the cells overexpressing GLUT 1 and GLUT 3. Myricetin also inhibited ascorbic acid uptake; inhibition was noncompetitive with K_i = 14 µmol/L in Jurkat cells. These data indicate that flavonoids inhibit both ascorbic acid and dehydroascorbic acid uptake but do so by different mechanisms. These data may contribute to new understanding of the biological effect of flavonoids on the intracellular accumulation of ascorbic acid in human cells.

KEY WORDS: • ascorbic acid • dehydroascorbic acid • U937 • HL-60 • and Jurkat • flavonoids • glucose transporters (GLUT 1 and GLUT 3)

This article has been cited by other articles:

				O. Kwon, P. Eck, S. Chen, C. P. Corpe, J.-H. Lee, M. Kruhlak, and M. Levine Inhibition of the intestinal glucose transporter GLUT2 by flavonoids FASEB J, February 1, 2007; 21(2): 366 - 377. [Abstract] [Full Text] [PDF]

				C. Biondi, B. Pavan, A. Dalpiaz, S. Medici, L. Lunghi, and F. Vesce Expression and characterization of vitamin C transporter in the human trophoblast cell line HTR-8/SVneo: effect of steroids, flavonoids and NSAIDs Mol. Hum. Reprod., January 1, 2007; 13(1): 77 - 83. [Abstract] [Full Text] [PDF]

				P. Cunningham, I. Afzal-Ahmed, and R. J. Naftalin Docking Studies Show That D-Glucose and Quercetin Slide through the Transporter GLUT1 J. Biol. Chem., March 3, 2006; 281(9): 5797 - 5803. [Abstract] [Full Text] [PDF]

				J. Song, O. Kwon, S. Chen, R. Daruwala, P. Eck, J. B. Park, and M. Levine Flavonoid Inhibition of Sodium-dependent Vitamin C Transporter 1 (SVCT1) and Glucose Transporter Isoform 2 (GLUT2), Intestinal Transporters for Vitamin C and Glucose J. Biol. Chem., May 3, 2002; 277(18): 15252 - 15260. [Abstract] [Full Text] [PDF]

				M. Levine, Y. Wang, S. J. Padayatty, and J. Morrow A new recommended dietary allowance of vitamin C for healthy young women PNAS, August 14, 2001; 98(17): 9842 - 9846. [Abstract] [Full Text] [PDF]