title: Relative suppression of the sodium-dependent Vitamin C transport in mouse versus human lens epithelial cells.
abstract: Vitamin C is a major antioxidant and UV absorbent in the human lens. In the rodent lens, the levels are very low for unknown reasons. Searching for clues to explain this suppression, we investigated the comparative uptake of Vitamin C in cultured human and mouse lens epithelial cells. When compared to human HLE-B3 lens epithelial cells, (14)C-ASA uptake was 4- to 10-fold impaired in confluent mouse lens 17EM15 (p < 0.0001) and 21EM15 (p < 0.001) cells, respectively. High glucose concentrations reduced the uptake by 30-50% in all cells (p < 0.005). Incubation of cells with 6-deoxy-6-fluoro-ascorbic (F-ASA), i.e. a probe specific for the sodium-dependent Vitamin C uptake (SVCT2), revealed a 10-fold uptake suppression into mouse 17EM15 relative to human HLE-B3 and JAR choriocarcinoma cells (a control), that could be overcome by overexpressing hSVCT2 using two different promoter constructs. The relative Vitamin C uptake differences suggest either low expression of SVCT2, molecular differences between the transporters themselves or their biological regulation, since a recent study has shown that exogenous feeding of ascorbic acid to rats increased only modestly lenticular uptake (Mody et al., Acta Ophthalmol Scand 83: 228-223, 2005). Elucidation of the mechanism by which SCVT2 activity is suppressed in mouse lens may help unravel a major question of evolutionary significance for night vision in nocturnal animals.
authors.affiliation: Department of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Obrenovich
authors.forename: Xingjun
authors.initials: X
authors.lastname: Fan
authors.forename: Makoto
authors.initials: M
authors.lastname: Satake
authors.forename: Simon M
authors.initials: SM
authors.lastname: Jarvis
authors.forename: Lixing
authors.initials: L
authors.lastname: Reneker
authors.forename: John R
authors.initials: JR
authors.lastname: Reddan
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Monnier
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001205:Ascorbic Acid / Q000031:analogs & derivatives / Q000378:metabolism*; D001692:Biological Transport; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D007908:Lens, Crystalline / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D029363:Organic Anion Transporters, Sodium-Dependent; C555163:SLC23A2 protein, human; C555165:Slc23a2 protein, mouse; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters; C076401:6-deoxy-6-fluoroascorbic acid; D001205:Ascorbic Acid