Ascorbic acid efflux from human brain microvascular pericytes: role of re-uptake

BioFactors
James M May, Zhi-Chao Qu

Abstract

Microvascular pericytes take up ascorbic acid on the ascorbate transporter SVCT2. Intracellular ascorbate then protects the cells against apoptosis induced by culture at diabetic glucose concentrations. To investigate whether pericytes might also provide ascorbate to the underlying endothelial cells, we studied ascorbate efflux from human pericytes. When loaded with ascorbate to intracellular concentrations of 0.8-1.0 mM, almost two-thirds of intracellular ascorbate effluxed from the cells over 2 H. This efflux was opposed by ascorbate re-uptake from the medium, since preventing re-uptake by destroying extracellular ascorbate with ascorbate oxidase increased ascorbate loss even further. Ascorbate re-uptake occurred on the SVCT2, since its blockade by replacing medium sodium with choline, by the SVCT2 inhibitor sulfinpyrazone, or by extracellular ascorbate accelerated ascorbate loss from the cells. This was supported by finding that net efflux of radiolabeled ascorbate was increased by unlabeled extracellular ascorbate with a half-maximal effect in the range of the high affinity Km of the SVCT2. Intracellular ascorbate did not inhibit its efflux. To assess the mechanism of ascorbate efflux, known inhibitors of volume-regulated a...Continue Reading

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Citations

Oct 12, 2019·Nutrients·Jens Lykkesfeldt, Pernille Tveden-Nyborg
May 10, 2017·Frontiers in Oncology·Christina WohlrabGabi U Dachs
Jun 18, 2019·Mediators of Inflammation·Paulina RudziakPaulina M Kowalewska
Jan 27, 2021·Free Radical Biology & Medicine·Sheetal PandayMahendra Kavdia

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