Polarized localization of vitamin C transporters, SVCT1 and SVCT2, in epithelial cells

Boyer, James C.; Campbell, Christine; Sigurdson, Wade J.; Kuo, Shiu‐Ming

doi:10.1016/j.bbrc.2005.06.069

Cited by 101 publications

(120 citation statements)

References 25 publications

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“…(The order of intracellular substrate dissociation is assumed.) Each carrier state is identified by a number (1)(2)(3)(4)(5)(6)(7)(8) and by a prime denoting that the carrier is at the external face of the membrane or double prime indicating the internal face. A Na ϩ uniport pathway or "internal leak," also electroneutral (n H Na ϭ 1), is shown as step 2 3 7.…”

Section: Discussionmentioning

confidence: 99%

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Transport model of the human Na⁺-coupled l-ascorbic acid (vitamin C) transporter SVCT1

Mackenzie¹,

Illing²,

Hediger³

2008

American Journal of Physiology-Cell Physiology

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Mackenzie B, Illing AC, Hediger MA. Transport model of the human Na ϩ -coupled L-ascorbic acid (vitamin C) transporter SVCT1. Am J Physiol Cell Physiol 294: C451-C459, 2008. First published December 19, 2007 doi:10.1152/ajpcell.00439.2007.-Vitamin C (L-ascorbic acid) is an essential micronutrient that serves as an antioxidant and as a cofactor in many enzymatic reactions. Intestinal absorption and renal reabsorption of the vitamin is mediated by the epithelial apical L-ascorbic acid cotransporter SVCT1 (SLC23A1). We explored the molecular mechanisms of SVCT1-mediated L-ascorbic acid transport using radiotracer and voltage-clamp techniques in RNA-injected Xenopus oocytes. L-Ascorbic acid transport was saturable (K0.5 Ϸ 70 M), temperature dependent (Q10 Ϸ 5), and energized by the Na ϩ electrochemical potential gradient. We obtained a Na ϩ -L-ascorbic acid coupling ratio of 2:1 from simultaneous measurement of currents and fluxes. L-Ascorbic acid and Na ϩ saturation kinetics as a function of cosubstrate concentrations revealed a simultaneous transport mechanism in which binding is ordered Na ϩ , L-ascorbic acid, Na ϩ . In the absence of L-ascorbic acid, SVCT1 mediated pre-steady-state currents that decayed with time constants 3-15 ms. Transients were described by single Boltzmann distributions. At 100 mM Na ϩ , maximal charge translocation (Qmax) was Ϸ25 nC, around a midpoint (V0.5) at Ϫ9 mV, and with apparent valence ϷϪ1. Qmax was conserved upon progressive removal of Na ϩ , whereas V0.5 shifted to more hyperpolarized potentials. Model simulation predicted that the pre-steady-state current predominantly results from an ion-well effect on binding of the first Na ϩ partway within the membrane electric field. We present a transport model for SVCT1 that will provide a framework for investigating the impact of specific mutations and polymorphisms in SLC23A1 and help us better understand the contribution of SVCT1 to vitamin C metabolism in health and disease. cotransporters; sodium dependent; intestinal absorption; model simulation; renal reabsorption; Xenopus oocyte VITAMIN C (L-ascorbic acid) is an essential micronutrient that serves as an antioxidant scavenger of free radicals and as a cofactor in many enzymatic reactions (3,6,10,26,29). It cannot be synthesized in Homo sapiens and must be derived from the diet. Intestinal absorption and renal reabsorption of the vitamin is mediated by the epithelial Na ϩ -dependent Lascorbic acid cotransporter SVCT1 (reviewed in Refs. 32 and 35), the product of the SLC23A1 gene. Selective sorting of SVCT1 protein to the apical membrane has been demonstrated in cultured cell lines (Caco2 and MDCK) of intestinal and renal origin (2, 23).We and others previously demonstrated that human SVCT1 is a Na ϩ -dependent transporter that favors L-ascorbic acid over D-isoascorbic acid and that the oxidized form of vitamin C, dehydroascorbic acid, is excluded (5, 34). Here we explored its molecular mechanisms by testing the hypothesis that the Na ϩ dependence and rheogenicity of SVCT1 arise from...

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Section: Discussionmentioning

confidence: 99%

“…32 and 35), the product of the SLC23A1 gene. Selective sorting of SVCT1 protein to the apical membrane has been demonstrated in cultured cell lines (Caco2 and MDCK) of intestinal and renal origin (2,23).…”

mentioning

confidence: 99%

Transport model of the human Na⁺-coupled l-ascorbic acid (vitamin C) transporter SVCT1

Mackenzie¹,

Illing²,

Hediger³

2008

American Journal of Physiology-Cell Physiology

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“…Hydropathy plot analyses predict that these two proteins have a 12 transmembrane spanning topology with cytoplasmic C and N terminal domains as well as multiple consensus sites for glycosylation and phosphorylation. SVCT1 and SVCT2 transporters share a 66 % amino acid homology (Boyer et al, 2005), although they are sorted into distinct membrane compartments in epithelial cells. Recently, the expression of SVCT transporters has been described in many cells types and transport results show that ascorbic acid uptake maintains the same kinetic characteristics (Maulén et al, 2003;Castro et al, 2007;.…”

Section: Vitamin C and Vitamin C Transportersmentioning

confidence: 99%

Vitamin C and oxidative stress in the seminiferous epithelium

et al. 2011

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In this article, we focus on the fundamental role of vitamin C transporters for the normal delivery of vitamin C to germ cells in the adluminal compartment of seminiferous tubules. We argue that the redox status within spermatozoa or in semen is partly responsible for the etiology of infertility. In this context, antioxidant defence plays a critical role in male fertility. Vitamin C, a micronutrient required for a wide variety of metabolic functions, has long been associated with male reproduction. Two systems for vitamin C transport have been described in mammals. Facilitative hexose transporters (GLUTs), with 14 known isoforms to date, GLUT1-GLUT14, transport the oxidized form of vitamin C (dehydroascorbic acid) into the cells. Sodium ascorbic acid co-transporters (SVCTs), SVCT1 and SVCT2 transport the reduced form of vitamin C (ascorbic acid). Sertoli cells control germ cell proliferation and differentiation through cell-cell communication and form the blood-testis barrier. Because the blood-testis barrier limits direct access of molecules from the plasma into the adluminal compartment of the seminiferous tubule, one important question is the method by which germ cells obtain vitamin C. Some interesting results have thrown light on this matter. Expression of SVCT2 and some isoforms of GLUT transporters in the testis have previously been described. Our group has demonstrated that Sertoli cells express functionally active vitamin C transporters. Kinetic characteristics were described for both transport systems (SVCT and GLUT systems). Sertoli cells are able to transport both forms of vitamin C. These fi ndings are extremely relevant, because Sertoli cells may control the amount of vitamin C in the adluminal compartment, as well as regulating the availability of this metabolite throughout spermatogenesis.

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“…These reactions may have little biologically relevance partly because of the poor bioavailability of vitamin C at high doses. The absorption and retention of vitamin C is limited by the transporter SVCT1 in the intestine and kidney, respectively [13]. As a result, the plasma concentration of vitamin C does not rise beyond 80 µM when daily intake increases over 20 folds above the required amount of ~100 mg to 2.5 g per day [4,5].…”

Section: Introductionmentioning

confidence: 99%

The Multifaceted Biological Roles of Vitamin C

Kuo¹

2013

J Nutr Food Sci

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Scurvy due to severe vitamin C (ascorbic acid) deficiency among sailors was one of the earliest documented occupational diseases. This review first discussed some reduction potential-based biochemical activities of vitamin C such as assisting the post-translational collagen modification as well as acting as an antioxidant and pro-oxidant. These known activities of vitamin C were then used to address recent outcomes of vitamin C clinical trials on the prevention and treatment of non-scurvy diseases such as cardiovascular diseases and cancer. The pro-oxidant activity may contribute to the adverse effect of high-level vitamin C supplementation in clinical trials.

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Polarized localization of vitamin C transporters, SVCT1 and SVCT2, in epithelial cells

Cited by 101 publications

References 25 publications

Transport model of the human Na⁺-coupled l-ascorbic acid (vitamin C) transporter SVCT1

Transport model of the human Na⁺-coupled l-ascorbic acid (vitamin C) transporter SVCT1

Vitamin C and oxidative stress in the seminiferous epithelium

The Multifaceted Biological Roles of Vitamin C

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Polarized localization of vitamin C transporters, SVCT1 and SVCT2, in epithelial cells

Cited by 101 publications

References 25 publications

Transport model of the human Na+-coupled l-ascorbic acid (vitamin C) transporter SVCT1

Transport model of the human Na+-coupled l-ascorbic acid (vitamin C) transporter SVCT1

Vitamin C and oxidative stress in the seminiferous epithelium

The Multifaceted Biological Roles of Vitamin C

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Product

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Transport model of the human Na⁺-coupled l-ascorbic acid (vitamin C) transporter SVCT1

Transport model of the human Na⁺-coupled l-ascorbic acid (vitamin C) transporter SVCT1