Differential regulation of the ascorbic acid transporter SVCT2 during development and in response to ascorbic acid depletion

• Published in: Biochemical and biophysical research communications Vol. 414; no. 4; pp. 737 - 742
• Main Authors: Meredith, M. Elizabeth, Harrison, Fiona E., May, James M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.11.2011
• Subjects: Animals; Ascorbic acid; Ascorbic Acid - metabolism; Biological Transport; Brain; Brain - embryology; Brain - growth & development; Brain - metabolism; Cerebellum - embryology; Cerebellum - growth & development; Cerebellum - metabolism; Cerebral Cortex - embryology; Cerebral Cortex - growth & development; Cerebral Cortex - metabolism; Development; Embryonic Development; Liver; Liver - embryology; Liver - growth & development; Liver - metabolism; Mice; Mice, Inbred C57BL; Oxidative Stress; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sodium-Coupled Vitamin C Transporters - genetics; Sodium-Coupled Vitamin C Transporters - metabolism; Sodium-dependent vitamin C transporter; ASC; Brain; Gulo; Ascorbic acid; Sodium-dependent vitamin C transporter; Liver; SVCT2; Development; OxS
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2011.09.146

► SVCT2 expression levels in brain are low during development and increase with age. ► In liver, SVCT2 levels are low during embryogenesis and increase post-natally. ► In adult mice, ASC does not regulate SVCT2 mRNA in cortex or cerebellum. ► Low ASC increases SVCT2 protein in the cerebellum of adult mice. ► Low ASC up-regulates SVCT2 mRNA and protein in liver in adult mice. The sodium-dependent vitamin C transporter-2 (SVCT2) is the only ascorbic acid (ASC) transporter significantly expressed in brain. It is required for life and is critical during brain development to supply adequate levels of ASC. To assess SVCT2 function in the developing brain, we studied time-dependent SVCT2 mRNA and protein expression in mouse brain, using liver as a comparison tissue because it is the site of ASC synthesis. We found that SVCT2 expression followed an inverse relationship with ASC levels in the developing brain. In cortex and cerebellum, ASC levels were high throughout late embryonic stages and early post-natal stages and decreased with age, whereas SVCT2 mRNA and protein levels were low in embryos and increased with age. A different response was observed for liver, in which ASC levels and SVCT2 expression were both low throughout embryogenesis and increased post-natally. To determine whether low intracellular ASC might be capable of driving SVCT2 expression, we depleted ASC by diet in adult mice unable to synthesize ASC. We observed that SVCT2 mRNA and protein were not affected by ASC depletion in brain cortex, but SVCT2 protein expression was increased by ASC depletion in the cerebellum and liver. The results suggest that expression of the SVCT2 is differentially regulated during embryonic development and in adulthood.