Molecular characterization of two novel transporters from human and mouse kidney and from LLC-PK1 cells reveals a novel conserved family that is homologous to bacterial and Aspergillus nucleobase transporters

Faaland, Carol A.; Race, JoAnne E.; Ricken, Gesa; Warner, Fern J.; Williams, William J.; Holtzman, Eliezer J.

doi:10.1016/s0167-4781(98)00151-1

Cited by 60 publications

(52 citation statements)

References 23 publications

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“…Kinetic analysis of vitamin C uptake has demonstrated that specialized cells, such as neurons, melanocytes, astrocytes, chromaffin cells, and fibroblasts, take up ascorbic acid (AA), the reduced form of vitamin C (Spector and Lorenzo, 1973;Siliprandi et al, 1979;Diliberto et al, 1983;Wilson, 1989;Welch et al, 1993;Spielholz et al, 1997;Zreik et al, 1999;Malo and Wilson, 2000;Castro et al, 2001). Two different isoforms of sodium-vitamin C cotransporters (SVCT1 and SVCT2) have been cloned (Faaland et al, 1998;Daruwala et al, 1999;Rajan et al, 1999;Tsukaguchi et al, 1999;Wang et al, 1999Wang et al, , 2000, these genes appear to belong to the family of solute carriers 23A (SLC23A1 and SLC23A2). Both SVCT proteins mediate high-affinity Na ϩ -dependent L-AA transport and are necessary for the uptake of vitamin C in many tissues.…”

Section: Introductionmentioning

confidence: 99%

“…Both SVCT proteins mediate high-affinity Na ϩ -dependent L-AA transport and are necessary for the uptake of vitamin C in many tissues. SVCT1 is a 604-amino acid protein that is expressed in epithelial cells of kidney, intestine, and liver (Faaland et al, 1998;Daruwala et al, 1999;Tsukaguchi et al, 1999). SVCT2 is a 592-amino acid protein that shares 65% homology to SVCT1 and has been detected mainly in brain and eyes (Rajan et al, 1999;Tsukaguchi et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

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Sodium vitamin C cotransporter SVCT2 is expressed in hypothalamic glial cells

García

Salazar

Millán

et al. 2004

Glia

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Kinetic analysis of vitamin C uptake demonstrated that different specialized cells take up ascorbic acid through sodium-vitamin C cotransporters. Recently, two different isoforms of sodium-vitamin C cotransporters (SVCT1/SLC23A1 and SVCT2/SLC23A2) have been cloned. SVCT2 was detected mainly in choroidal plexus cells and neurons; however, there is no evidence of SVCT2 expression in glial and endothelial cells of the brain. Certain brain locations, including the hippocampus and hypothalamus, consistently show higher ascorbic acid values compared with other structures within the central nervous system. However, molecular and kinetic analysis addressing the expression of SVCT transporters in cells isolated from these specific areas of the brain had not been done. The hypothalamic glial cells, or tanycytes, are specialized ependymal cells that bridge the cerebrospinal fluid with different neurons of the region. Our hypothesis postulates that SVCT2 is expressed selectively in tanycytes, where it is involved in the uptake of the reduced form of vitamin C (ascorbic acid), thereby concentrating this vitamin in the hypothalamic area. In situ hybridization and optic and ultrastructural immunocytochemistry showed that the transporter SVCT2 is highly expressed in the apical membranes of mouse hypothalamic tanycytes. A newly developed primary culture of mouse hypothalamic tanycytes was used to confirm the expression and function of the SVCT2 isoform in these cells. The results demonstrate that tanycytes express a high-affinity transporter for vitamin C. Thus, the vitamin C uptake mechanisms present in the hypothalamic glial cells may perform a neuroprotective role concentrating vitamin C in this specific area of the brain.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sodium vitamin C cotransporter SVCT2 is expressed in hypothalamic glial cells

García

Salazar

Millán

et al. 2004

Glia

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“…Chimeric and mutational protein analysis of UapA and UapC has revealed a domain involved in purine transport and specificity and a conserved domain, which constitutes a signature sequence for this group of transporters (Diallinas et al, 1998). Human, pig, and mouse homologues of nucleobase transporters have recently been identified (Guimaraes et al, 1995;Diallinas et al, 1998;Faaland et al, 1998).…”

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confidence: 99%

Protein Expression and Subcellular Localization of the General Purine Transporter UapC from Aspergillus nidulans

Taubas

Diallinas

Scazzocchio

et al. 2000

Fungal Genetics and Biology

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“…Oxidized vitamin C, dehydroascorbic acid (DHA) is taken up by facilitative hexose transporters (GLUT-1, -3 and -4) and then intracellularly reduced to ascorbic acid (AA) (Liang et al 2001;Nualart et al 2003). On the other hand, two diVerent isoforms of high aYnity sodium-dependent vitamin C co-transporters (SVCT1 and SVCT2) mediate AA transport (Faaland et al 1998;Daruwala et al 1999;Rajan et al 1999;Tsukaguchi et al 1999;Wang et al 2000;Savini et al 2008). SVCT1 has been associated to vitamin C absorption as it is mainly expressed in epithelial tissues, like intestine and kidney (Faaland et al 1998;Daruwala et al 1999;Tsukaguchi et al 1999;Castro et al 2008).…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, two diVerent isoforms of high aYnity sodium-dependent vitamin C co-transporters (SVCT1 and SVCT2) mediate AA transport (Faaland et al 1998;Daruwala et al 1999;Rajan et al 1999;Tsukaguchi et al 1999;Wang et al 2000;Savini et al 2008). SVCT1 has been associated to vitamin C absorption as it is mainly expressed in epithelial tissues, like intestine and kidney (Faaland et al 1998;Daruwala et al 1999;Tsukaguchi et al 1999;Castro et al 2008). In turn, SVCT2 displays higher aYnity and lower capacity to transport AA than SVCT1 and it is widely expressed in several metabolically active and specialized cells and tissues (Rajan et al 1999;Tsukaguchi et al 1999;Castro et al 2001).…”

Section: Introductionmentioning

confidence: 99%

The ascorbic acid transporter SVCT2 is expressed in slow-twitch skeletal muscle fibres

Low

Sandoval

Avilés

et al. 2009

Histochem Cell Biol

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Ascorbic acid, the reduced form of vitamin C, functions as a potent antioxidant as well as in cell differentiation. Ascorbate is taken up by mammalian cells through the specific sodium/ascorbate co-transporters SVCT1 and SVCT2. Although skeletal muscle contains about 50% of the whole-body vitamin C, the expression of SVCT transporters has not been clearly addressed in this tissue. In this work, we analysed the expression pattern of SVCT2 during embryonic myogenesis using the chick as model system. We cloned the chick orthologue of SVCT2 (cSVCT2) that shares 93% identity with the mouse transporter. cSVCT2 mRNA and protein are expressed during chick embryonic muscle development. Immunohistochemical analyses showed that SVCT2 is preferentially expressed by type I slow-twitch muscle fibres throughout chick myogenesis as well as in post-natal skeletal muscles of several species, including human. Our results suggest that SVCT2-mediated uptake of ascorbate is relevant to the oxidative nature of type I muscle fibres.

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Molecular characterization of two novel transporters from human and mouse kidney and from LLC-PK1 cells reveals a novel conserved family that is homologous to bacterial and Aspergillus nucleobase transporters

Cited by 60 publications

References 23 publications

Sodium vitamin C cotransporter SVCT2 is expressed in hypothalamic glial cells

Sodium vitamin C cotransporter SVCT2 is expressed in hypothalamic glial cells

Protein Expression and Subcellular Localization of the General Purine Transporter UapC from Aspergillus nidulans

The ascorbic acid transporter SVCT2 is expressed in slow-twitch skeletal muscle fibres

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