Disease relevance of SLC23A1

• We have mapped the SLC23A2 gene (coding for SVCT1) to human chromosome 5 in band 5q31.2-31.3, within a region commonly deleted in malignant myeloid (leukemia) diseases [1].
• Neurodegenerative diseases with an established role for oxidative stress in the cytoplasm may therefore be conditions of SLC23A1 dysfunction [2].
• METHOD: Ninety-seven patients, who had honeycombing associated with end-stage pulmonary fibrosis on end-inspiratory 1 to 2 mm collimation high-resolution CT (HRCT), underwent I-E SVCT (3 mm collimation, pitch 1, breath-hold time 20 s, reconstruction interval 1 mm, FOV 16-20 cm, high frequency algorithm) [3].
• CONCLUSIONS: We suggest that the combination of precontrast SVCT and CT-ADP is an essential modality to screen for HCC in patients with chronic liver disease [4].

High impact information on SLC23A1

• Despite their close sequence homology and similar functions, the two isoforms of the transporter are discretely distributed: SVCT1 is mainly confined to epithelial systems (intestine, kidney, liver), whereas SVCT2 serves a host of metabolically active cells and specialized tissues in the brain, eye and other organs [5].
• Vitamin C is transported as ascorbic acid (AA) through the sodium-ascorbate cotransporters (SVCT1 and -2) and as dehydroascorbic acid (DHA) through the facilitative glucose transporters [6].
• Vitamin C intracellular accumulation is mediated by Na(+)-dependent vitamin C transporters SVCT1 and -2 and dehydroascorbic acid transporters GLUT1 and -3 [7].
• In human fibroblasts, predicted to have SVCT-mediated ascorbate accumulation, K(m) and V(max) values were again comparable for ascorbic acid and 6-bromo-6-deoxy-L-ascorbic acid [7].
• A C-terminal region dictates the apical plasma membrane targeting of the human sodium-dependent vitamin C transporter-1 in polarized epithelia [8].

Biological context of SLC23A1

• Our results provide the first direct resolution of functional hSVCT1 expression at the apical cell surface of polarized epithelia and define an apical targeting signal of relevance to transporters of diverse substrate specificity [8].
• Up-regulation and polarized expression of the sodium-ascorbic acid transporter SVCT1 in post-confluent differentiated CaCo-2 cells [9].
• By progressive truncation of the cytoplasmic C-terminal tail of hSVCT1, we delimited an essential role for an embedded ten amino acid sequence PICPVFKGFS (amino acids 563-572) in defining the physiological targeting of hSVCT1 [8].
• Potential sites for phosphorylation by protein kinase C exist on the cytoplasmic surface of both proteins, with an additional protein kinase A site in SVCT1 [10].
• The two isoforms also differ in their tissue distribution: SVCT1 is present in epithelial tissues, whereas SVCT2 is present in most tissues with the exception of lung and skeletal muscle [10].

Anatomical context of SLC23A1

• Applying radiotracer and voltage-clamp approaches in cRNA-injected Xenopus oocytes, we found that SVCT1 mediates saturable, concentrative, high-affinity l-ascorbic acid transport (K(0.5) = 50-100 microM) that is electrogenic and can be inhibited by phloretin [1].
• SVCT1 is largely confined to bulk-transporting epithelia (e.g., kidney and small intestine) with a putative alternative-splice product present in thymus [1].
• By means of RT-PCR, we found that SVCT2, but not SVCT1, mRNA is expressed in human trophoblast cell line HTR-8/SVneo [11].
• Confocal imaging demonstrated that hSVCT1 was expressed at the apical cell surface and video rate measurements revealed hSVCT1 also resided in a heterogeneous population of intracellular organelles with discrete dynamic properties [8].
• Protein kinase C (PKC) regulation of l-ascorbic acid transport mediated by the Na+/ascorbic acid transporters, hSVCT1 and hSVCT2, expressed in COS-1 cells was studied using recombinant carboxyl-terminal V5 epitope-tagged forms of the transporters [12].

Associations of SLC23A1 with chemical compounds

• In addition, we have demonstrated that the human SLC23A1 gene product is a related high-affinity l-ascorbic acid transporter (SVCT2) that is widely distributed in brain, retina, and a host of endocrine and neuroendocrine tissues [1].
• Differentiated SH-SY5Y cells in culture took up ascorbic acid on the sodium-dependent vitamin C transporter Type 2 and retained it much more effectively than dehydroascorbic acid [13].
• I-E SVCT scans were assessed on images obtained in the transverse plane and volumetric sagittal, coronal, and oblique reformations [3].

Other interactions of SLC23A1

• Vitamin C is actively transported into cells by one of two closely related sodium-dependent transporters, SVCT1 or SVCT2 [14].

Analytical, diagnostic and therapeutic context of SLC23A1

• We describe here the molecular cloning of a novel human cDNA encoding a vitamin C transporter SVCT1 [1].
• Analysis by real time quantitative PCR revealed that the post-confluent differentiation of CaCo-2 cells was accompanied by a marked increase (4-fold) in the steady-state level of SVCT1 mRNA, without changes in SVCT2 mRNA levels [9].
• Western blot and confocal microscopy analyses indicated that the total pool of hSVCT1 or hSVCT2 proteins expressed in the transfected COS-1 cells remained unaffected by PMA treatment [12].
• PURPOSE: The purpose of this study was twofold: to evaluate the change in size of honeycomb cysts with respiration using inspiratory-expiratory spiral volumetric CT (I-E SVCT) and to establish the pathologic basis of this change [3].
• The main aim of the present study is to evaluate the detectability of hypervascular HCC with SVCT as compared with ultrasonography (US) and magnetic resonance (MR) imaging [4].

References