title: The human sodium-dependent ascorbic acid transporters SLC23A1 and SLC23A2 do not mediate ascorbic acid release in the proximal renal epithelial cell.
abstract: Sodium-dependent ascorbic acid membrane transporters SLC23A1 and SLC23A2 mediate ascorbic acid (vitamin C) transport into cells. However, it is unknown how ascorbic acid undergoes cellular release, or efflux. We hypothesized that SLC23A1 and SLC23A2 could serve a dual role, mediating ascorbic acid cellular efflux as well as uptake. Renal reabsorption is required for maintaining systemic vitamin C concentrations. Because efflux from nephron cells is necessary for reabsorption, we studied whether SLC23A1 and SLC23A2 mediate efflux of ascorbic acid in the human renal nephron. We found high gene expression of SLC23A1 but no expression of SLC23A2 in the proximal convoluted and straight tubules of humans. These data rule out SLC23A2 as the ascorbic acid release protein in the renal proximal tubular epithelia cell. We utilized a novel dual transporter-based Xenopus laevis oocyte system to investigate the function of the SLC23A1 protein, and found that no ascorbate release was mediated by SLC23A1. These findings were confirmed in mammalian cells overexpressing SLC23A1. Taken together, the data for SLC23A1 show that it too does not have a role in cellular release of ascorbic acid across the basolateral membrane of the proximal tubular epithelial cell, and that SLC23A1 alone is responsible for ascorbic acid uptake across the apical membrane. These findings reiterate the physiological importance of proper functioning of SLC23A1 in maintaining vitamin C levels for health and disease prevention. The ascorbate efflux mechanism in the proximal tubule of the kidney remains to be characterized.
authors.affiliation: Department of Human Nutritional Sciences, University of Manitoba Winnipeg, Manitoba, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Eck
authors.affiliation: Department of Nutritional Science & Food Management, Ewha Womans University Seoul, Republic of Korea.
authors.forename: Oran
authors.initials: O
authors.lastname: Kwon
authors.affiliation: Molecular and Clinical Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health Bethesda, 20892, Maryland.
authors.forename: Shenglin
authors.initials: S
authors.lastname: Chen
authors.affiliation: Radiation Oncology, Johns Hopkins Hospital Baltimore, Maryland.
authors.forename: Omar
authors.initials: O
authors.lastname: Mian
authors.affiliation: Molecular and Clinical Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health Bethesda, 20892, Maryland.
authors.forename: Mark
authors.initials: M
authors.lastname: Levine
keywords: Ascorbic acid release; SLC23A1; SLC23A2; kidney; proximal tubule