Decreased expression of the vitamin C transporter SVCT1 by ascorbic acid in a human intestinal epithelial cell line.
Vitamin C (ascorbic acid) is an essential nutrient that is involved in a number of cellular processes. However, unlike most mammals, man is unable to synthesize vitamin C and it must therefore be acquired from the diet. Absorption of vitamin C is achieved by two transporters, SVCTI and SVCT2, recently cloned from rat and human kidney. SVCT1 is thought to be the predominant transporter in the intestine. Vitamin C supplements are increasingly common, thus contributing to an increased dietary load, and therefore the aim of the present study was to investigate the effect of high doses of ascorbic acid on SVCT1 expression. Using the Caco-2 TC7 cell model of small intestinal enterocytes, we measured the effects of ascorbic acid (4.5 mg/ml culture medium) on L-[14C]ascorbic acid uptake and SVCT1 expression (determined by reverse transcription-polymerase chain reaction). Ascorbic acid uptake was decreased significantly in Caco-2 TC7 cells exposed to ascorbate for 24 h (-50%, P<0.0005). Expression of SVCT1 was also significantly reduced by exposure to elevated levels of ascorbate for 24h (-77%, P<0.005). Taken together these results suggest that high-dose supplements might not be the most efficient way of increasing the body pool of vitamin C.
MacDonald
Lauren
L
Centre for Nutrition and Food Safety, School of Biomedical and Life Sciences, University of Surrey, Guildford, UK.
Thumser
Alfred E
AE
Sharp
Paul
P
D001205:Ascorbic Acid / Q000493:pharmacokinetics / Q000494:pharmacology*; D018938:Caco-2 Cells; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D029363:Organic Anion Transporters, Sodium-Dependent; D011506:Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters
D029363:Organic Anion Transporters, Sodium-Dependent; D011506:Proteins; C555162:SLC23A1 protein, human; C555163:SLC23A2 protein, human; C555166:Slc23a1 protein, rat; C555167:Slc23a2 protein, rat; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters; D001205:Ascorbic Acid