Low vitamin C and increased oxidative stress and cell death in mice that lack the sodium-dependent vitamin C transporter SVCT2.

Harrison FE, Dawes SM, Meredith ME, Babaev VR, Li L, May JM
Free Radic Biol Med. 2010 49 (5): 821-9

PMID: 20541602 · PMCID: PMC2916678 · DOI:10.1016/j.freeradbiomed.2010.06.008

The sodium-dependent vitamin C transporter (SVCT2) is responsible for the transport of vitamin C into cells in multiple organs, from either the blood or the cerebrospinal fluid. Mice null for SVCT2 (SVCT2(-/-)) do not survive past birth but the cause of death has not yet been ascertained. After mating of SVCT2(+/-) males and SVCT2(+/-) females, fewer SVCT2(-/-) and SVCT2(+/-) progeny were observed than would be expected according to Mendelian ratios. Vitamin C levels in SVCT2(-/-), SVCT2(+/-), and SVCT2(+/+) were genotype-dependent. SVCT2(-/-) fetuses had significantly lower vitamin C levels than littermates in placenta, cortex, and lung, but not in liver (the site of vitamin C synthesis). Low vitamin C levels in placenta and cortex were associated with elevations in several markers of oxidative stress: malondialdehyde, isoketals, F(2)-isoprostanes, and F(4)-neuroprostanes. Oxidative stress was not elevated in fetal SVCT2(-/-) lung tissue despite low vitamin C levels. In addition to the expected severe hemorrhage in cortex, we also found hemorrhage in the brain stem, which was accompanied by cell loss. We found evidence of increased apoptosis in SVCT2(-/-) mice and disruption of the basement membrane in fetal brain. Together these data show that SVCT2 is critical for maintaining vitamin C levels in fetal and placental tissues and that the lack of SVCT2, and the resulting low vitamin C levels, results in fetal death and, in SVCT2(-/-) mice that survive the gestation period, in oxidative stress and cell death.

Copyright 2010 Elsevier Inc. All rights reserved.

MeSH Terms (20)

Animals Ascorbic Acid Brain Cell Death Down-Regulation Female Genotype Male Malondialdehyde Mice Mice, Inbred C57BL Mice, Transgenic Organic Anion Transporters, Sodium-Dependent Oxidative Stress Placenta Pregnancy Sodium-Coupled Vitamin C Transporters Symporters Tissue Distribution Up-Regulation

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