title: Molecular mechanism(s) involved in differential expression of vitamin C transporters along the intestinal tract.
abstract: Mammalian cells utilize two transporters for the uptake of ascorbic acid (AA), Na+-dependent vitamin C transporter SVCT-1 and SVCT-2. In the intestine, these transporters are involved in AA absorption and are expressed at the apical and basolateral membrane domains of the polarized epithelia, respectively. Little is known about the differential expression of these two transporters along the anterior-posterior axis of the intestinal tract and the molecular mechanism(s) that dictate this pattern of expression. We used mouse and human intestinal cDNAs to address these issues. The results showed a significantly lower rate of carrier-mediated AA uptake by mouse colon than jejunum. This was associated with a significantly lower level of expression of SVCT-1 and SVCT-2 at the protein, mRNA, and heterogeneous nuclear RNA (hnRNA) levels in the colon than the jejunum, implying the involvement of transcriptional mechanism(s). Similarly, expression levels of SVCT-1 and SVCT-2 mRNA and hnRNA were significantly lower in human colon. We also examined the levels of expression of hepatocyte nuclear factor 1α and specificity protein 1, which drive transcription of theSlc23a1andSlc23a2promoters, respectively, and found them to be markedly lower in the colon. Furthermore, significantly lower levels of the activating markers for histone (H3) modifications [H3 trimethylation of lysine 4 (H3K4me3) and H3 triacetylation of lysine 9 (H3K9ac)] were observed in theSlc23a1andSlc23a2promoters in the colon. These findings show, for the first time, that SVCT-1 and SVCT-2 are differentially expressed along the intestinal tract and that this pattern of expression is, at least in part, mediated via transcriptional/epigenetic mechanisms.NEW & NOTEWORTHYOur findings show, for the first time, that transporters of the water-soluble vitamin ascorbic acid (i.e., the vitamin C transporters SVCT-1 and SVCT-2) are differentially expressed along the length of the intestinal tract and that the pattern of expression is mediated, at least in part, by transcriptional and epigenetic mechanism(s) affecting bothSlc23a1andSlc23a2genes.
authors.affiliation: Departments of Medicine, Physiology, and Biophysics, University of California, Irvine, California; vsubrama@uci.edu.|Department of Veterans Affairs Medical Center, Long Beach, California; and.
authors.forename: Veedamali S
authors.initials: VS
authors.lastname: Subramanian
authors.affiliation: Departments of Medicine, Physiology, and Biophysics, University of California, Irvine, California.|Department of Veterans Affairs Medical Center, Long Beach, California; and.
authors.forename: Padmanabhan
authors.initials: P
authors.lastname: Srinivasan
authors.affiliation: Department of Veterans Affairs Medical Center, Long Beach, California; and.
authors.forename: Alexis J
authors.initials: AJ
authors.lastname: Wildman
authors.affiliation: Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Marchant
authors.affiliation: Departments of Medicine, Physiology, and Biophysics, University of California, Irvine, California.|Department of Veterans Affairs Medical Center, Long Beach, California; and.
authors.forename: Hamid M
authors.initials: HM
authors.lastname: Said
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D003106:Colon / Q000378:metabolism*; D019175:DNA Methylation; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007583:Jejunum / Q000378:metabolism*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D060347:Sodium-Coupled Vitamin C Transporters / Q000378:metabolism*; D055815:Young Adult
chemical_list: D060347:Sodium-Coupled Vitamin C Transporters
keywords: SVCT-1; SVCT-2; differential expression; intestine; uptake; vitamin C