Flavonoid inhibition of sodiumdependent vitamin c transporter 1 svct1 and glucose transporter isoform 2. Molecular characterization and transcriptional regulation of the sodiumdependent vitamin c transporter genes slc23a1 and slc23a2 in a teleost fish. Sodium dependent vitamin c transporter 1 svct1 antibody. Sodiumdependent multivitamin transporter is a protein that in humans is encoded by the slc5a6 gene. Ascorbate is absorbed via active transport in the small intestine through sodiumdependent vitamin c transporter 1 svct1. In vivo middle cerebral artery occlusion experiments were tested to determine. Flavonoid inhibition of sodiumdependent vitamin c transporter 1 svct1 and glucose transporter isoform 2 glut2. Cultured embryonic fibroblasts from homozygous slc23a1 mice had less than 5% of normal ascorbicacid uptake. Pdf molecular characterization and transcriptional. Am j physiol gastrointest liver physiol, 304, g1079 g1086. Serotonin, protein kinase c, and hic5associated redistribution of the platelet serotonin transporter. Corpe, 1 hongbin tu, 1 peter eck, 1 jin wang, 1 robert faulhaberwalter, 2 jurgen schnermann, 2 sam margolis, 1 sebastian padayatty, 1 he sun, 3 yaohui wang, 1 robert l.
Genomic and functional analysis of the sodiumdependent vitamin c transporter slc23a1svct1. Unless otherwise stated all data on this page refer to the human proteins. A functional role for sodiumdependent glucose transport. Svct1 and svct2 display similar properties, including high affinity for lascorbic acid, but are discretely distributed. Sodiumdependent vitamin c transporter2 mediates vitamin c. Flavonoids, such as the dietary component quercetin, reversibly inhibit vitamin c uptake in human colon cancer cells and rat nontransformed intestinal crypt cells, as well as in chinese hamster ovary cells and xenopus laevis oocytes transfected with human sodiumdependent vitamin c transporter svct1 52, 86.
Pathway commonssodiumdependent multivitamin transporter. Vitamin c is taken up by human t cells via sodiumdependent. Abstractsodium dependent ascorbic acid membrane transporters slc23a1 and slc23a2 mediate ascorbic acid. Subcellular redistribution of the serotonin transporter by secretory carrier membrane protein 2. Reduced vitamin c ascorbic acid aa, which is taken up into cells by sodiumdependent vitamin c transporter svct 1 and 2, is believed to be important for hormone synthesis, but its role in generating placental steroids needed to maintain pregnancy and fetal development is not clear. The objective of this research was to functionally characterize sodiumdependent vitamin c transporter svct in mdckmdr1 cells and to study the effect of substituted benzene derivatives on the intracellular accumulation of ascorbic acid aa. Nussbaum,4 michael graham espey, 1 and mark levine. Glucose transporter glut 1 and sodium glucose cotransporter sglt activity were investigated by luminal membrane uptake and transport studies using 3 h dglucose and also by 14 c.
When glucose and quercetin were coadministered orally in zucker fafa rats, quercetin. Ascorbic acid and sodiumdependent vitamin c transporters svct have been shown to have important functions in the. Svct1 and svct2 display similar properties, including high affinity for lascorbic acid, but are. We have created mice deficient in the mouse ortholog solute carrier family 23 member 1 or slc23a1 of a rat ascorbicacid transporter, svct2 ref. To elucidate, we isolated human peripheral blood t cells and analyzed the expression of sodium dependent vitamin c transporters svct. Prasad, 2 ibrahim zakhary, 4 matthew bowser, 3 carlos isales, 1 and vadivel ganapathy 2. Slc23a1 solute carrier family 23 member 1 homo sapiens. Quizlet flashcards, activities and games help you improve your grades. Vitamin c transporter slc23a1 links renal reabsorption, vitamin c tissue accumulation, and perinatal survival in mice christopher p. Glyoxalate reductasehydroxypyruvate reductase interacts with the sodiumdependent vitamin c transporter 1 to regulate cellular vitamin c homeostasis veedamali s.
The dominant transport mechanism in most tissues, including colonic epithelium, is sodiumdependent transport based on the evidence that dehydroascorbic acid is not found in blood and that vitamin c accumulation is virtually eliminatedin most tissues in the slc23a2 svct2 knockout mouse. Department of sleep medicine and neuromuscular disorders, university hospital muenster, muenster, germany. Inhibition of intestinal ascorbic acid uptake by lipopolysaccharide is. Sodiumdependent vitamin c transporter vitamin c ascorbic acid, aa is required for mammalian cell growth and normal cell function, and plays an essential role among the mechanisms of defence against free radicals and as an enzyme cofactor 1. The tissue distribution, cellular and subcellular localization of the sodiumdependent ascorbic acid transporter 3 svct3 were characterized. Ascorbic acid and sodiumdependent vitamin c transporters in the. Most cells express two different transporter systems for vitamin c. Vitamin c is a wide spectrum antioxidant essential for humans, which are unable to synthesize the vitamin and must obtain it from dietary sources. Glucose modulates vitamin c transport in adult human small. Aug 24, 2011 the bass2 protein is localized at the chloroplast envelope membrane, and is highly abundant in c 4 plants that have the sodium dependent pyruvate transporter. Previously, this gene had an official symbol of slc23a2. Although different aspects of hsvct1 cell biology have been extensively studied, nothing is currently known about the broader hsvct1 interactome that modulates its role in cellular physiology. Similarly, brain tissues from glioblastoma patients also display reduction of glt 1 and mislocalization of glast.
Other forms of vitamin c transport include the release of vitamin c from secretory vesicles and active transport. However, in glioma cells, essentially all glast protein was found in cell nuclei rather than the plasma membrane. Genetic variants in sodiumdependent vitamin c transporter proteins svcts, slc23a1 and slc23a2 6 are not subject to these concerns. Dec 15, 2005 however, the dominant mechanism of vitamin c accumulation in most tissues is sodium dependent transport by svct1 and svct2, based on evidence that ascorbic acid is found in blood, but dehydroascorbic acid is not, and that vitamin c accumulation is virtually eliminated in most tissues in the slc23a2 e. Previously, this gene had an official symbol of slc23a1. The c aryl glucoside 6 dapagliflozin was identified as a potent and selective hsglt2 inhibitor which reduced blood glucose levels in a dose dependent manner by as much as 55% in hyperglycemic streptozotocin stz rats. Flavonoid inhibition of sodiumdependent vitamin c transporter 1 svct1 and glucose transporter isoform 2 glut2, intestinal transporters for vitamin c. To elucidate, we isolated human peripheral blood t cells and analyzed the expression of sodiumdependent vitamin c transporters svct. Sodium dependent vitamin c transporter 1 svct1 antigen profile protein summary the absorption of vitamin c into the body and its distribution to organs requires two sodiumdependent vitamin c transporters. They show distinct tissue distribution and functional characteristics, which. Modulation of function of sodiumdependent vitamin c. Genomic and functional analysis of the sodiumdependent. This is dominated in cancer cells by glut1 transport of dha, with svcts either not expressed or having low activity due. Gene information is provided for human hs, mouse mm and rat rn.
Studies utilizing caco2 cells and rab8a knockout mice. Human skin contains relatively high concentrations of vitamin c in the dermis, with higher levels found in the epidermis. Slc23 family of ascorbic acid transporters c unless otherwise stated all data on this page refer to the human proteins. Sodiumdependent vitamin c transporter 2 is also known to be downregulated by inflammatory cytokines such as interleukin 1 and tumor necrosis factor. Taken together the results indicate that svct3 is an interesting and promising. Mechanism of aa uptake and transport was delineated. Slc23 family of ascorbic acid transporters transporters.
Slc19 family of vitamin transporters c iupharbps guide to. Sodiumdependent vitamin c transporter2 mediates vitamin c transport at the cortical nerve terminal. Both these transporters contain potential sites for nglycosylation in their extracellular domains asn8, asn144 hsvct1. Vitamin c is actively accumulated into the epidermal and dermal cells via the two sodiumdependent vitamin c transporter svct isoforms 1 and 2 27, suggesting that the vitamin has crucial functions within the skin. Requirement of calcium and phosphate ions in expression of sodiumdependent vitamin c transporter 2 and osteopontin in mc3t3e1 osteoblastic cells. Svct3 slc23a3 expression is largely restricted to the kidney and localized in the renal proximal straight tubule segments. Antihuman sodiumdependent vitaminc transporter 2 svct2. This gene encodes one of the two required transporters and the encoded protein accounts for tissuespecific uptake of vitamin c. Using immunohistochemistry, immunoblotting, and reverse transcription pcr, we could show that.
The absorption of vitamin c into the body and its distribution to organs requires two sodium dependent vitamin c transporters. In order to examine the possible contribution of host genetic variation in the major transport system for vitamin c, we con ducted an association study in a nested case control study of snps in the sodium dependent vitamin c transporters svct1 encoded by slc23a1 and svct2 encoded by slc23a2 and colorectal adenoma, an early precursor for. It is a putative transporter for uptake of biotin and pantothenic acid at the bloodbrain barrier. Corpe,1 hongbin tu, 1 peter eck, jin wang,1 robert faulhaberwalter,2 jurgen schnermann,2 sam margolis, 1 sebastian padayatty, he sun,3 yaohui wang,1 robert l. Sodiumdependent multivitamin transporter how is sodium. Sodium dependent multivitamin transporter is a protein that in humans is encoded by the slc5a6 gene it is a putative transporter for uptake of biotin and pantothenic acid at the bloodbrain barrier. Mechanism of vitamin c transport, in both reduced aa and oxidized dha forms, by sodiumdependent vitamin c transporters 1 and 2 svct 1, 2 and glucose transporters primarily glut1, 3 and also glut 4, respectively. Highaffinity sodiumdependent uptake of ascorbic acid by rat osteoblasts. The human sodiumdependent vitamin c transporter 1 hsvct1 contributes to cellular uptake of ascorbic acid aa.
What is the abbreviation for sodiumdependent vitamin c transporter. Abstractvitamin c vitc has several roles in the brain acting both as a specific and nonspecific antioxidant. Sodium dependent vitamin c transporter 1 svct1 protein profile protein summary the absorption of vitamin c into the body and its distribution to organs requires two sodiumdependent vitamin c transporters. Fulzele s 1, chothe p, sangani r, chutkan n, hamrick m, bhattacharyya m, prasad pd, zakhary i, bowser m, isales c, ganapathy v.
Microrna103a regulates sodiumdependent vitamin c transporter 1 expression in intestinal epithelial cells author links open overlay panel veedamali s. Jian song, oran kwon, shenglin chen, rushad daruwala, peter eck, jae b park, mark levine pmid 11834736. Glyoxalate reductasehydroxypyruvate reductase interacts with the sodium dependent vitamin c transporter 1 to regulate cellular vitamin c homeostasis. Studies have shown a role for the rab8a in the apical membrane targeting of transporters in intestinal cells.
Flavonoids reversibly inhibited vitamin c transport in transfected cells with ic 50 values of 1050. Chronic vitamin c deficiency promotes redox imbalance in the. Sodiumdependent vitamin c transporter 1 slc23a1 is expressed in the epithelial tissue of kidney, intestine, liver, lung, and skin. Genetic variation in the sodiumdependent vitamin c. Expression, function, and regulation in intervertebral disc cells, abstract background context. Sodiumdependent vitamin c transporter 2 svct2 is necessary for. Svct abbreviation stands for sodiumdependent vitamin c transporter. Hydropathy plot kytedolittle algorithm revealed that human smvt protein consists of 635 amino. Svct1 sodiumdependent vitamin c transporter 1 slc23a1 c show summary.
Human intestine expresses two sodiumdependent vitamin c transporters hsvct1 and 2 that mediate cellular aa transport, with hsvct1 targeting to the apical membrane of polarized epithelia. Flavonoid inhibition of sodiumdependent vitamin c transporter 1 svct1 and glucose transporter isoform 2 glut2, intestinal transporters for vitamin c and. Fulzele s1, chothe p, sangani r, chutkan n, hamrick m, bhattacharyya m, prasad pd, zakhary i, bowser m, isales c, ganapathy v. There are reports that suggest agedependent decrease in uptake and recycling of aa in erythrocytes of beagle dogs 37 and rat hepatocytes 38, 39. Nomenclature the transporter for ascorbate was cloned in 1999 and given the trivial name of sodiumdependent vitamin c transporter, abbreviated svct tsukaguchi et al. This article is from physiological reports, volume 1. The human sodiumdependent ascorbic acid transporters slc23a1. Expression and function in bone marrow stromal cells and in osteogenesis sadanand fulzele a. The sodiumdependent ascorbic acid transporter family slc23. Sodium dependent vitamin c transporter 1 elisa kits. Compromised glutamate transport in human glioma cells.
We investigated the effects of selected flavonoids on the intestinal vitamin c transporter svct1h by transfecting and overexpressing svct1h in chinese hamster ovary cells. Flavonoid inhibition of sodium dependent vitamin c transporter 1 svct1 and glucose transporter isoform 2 glut2, intestinal transporters for vitamin c and glucose. Sodiumdependent multivitamin transporter wikipedia. Molecular characterization and transcriptional regulation. Sodium dependent vitamin c transporter 1 svct1 antibodies. The human sodiumdependent vitamin c transporters hsvct1 and hsvct2 mediate cellular uptake of ascorbic acid. Occurs throughout the small intestine by sodium dependent vitamin c transporter svct1, svct2 can vitamin c be absorbed by simple diffusion. Modulation of function of sodium dependent vitamin c transporter 1 svct1 by rab8a in intestinal epithelial cells. Abhisek ghosal senior scientist researchdx linkedin. Modulation of function of sodiumdependent vitamin c transporter 1 svct1 by rab8a in intestinal epithelial cells. Sodium dependent vitamin c transporter 1 svct1 elisa kits. A plastidial sodiumdependent pyruvate transporter nature. Expression and function in bone marrow stromal cells and in osteogenesis sadanand fulzele, 1 paresh chothe, 2 rajnikumar sangani, 1 norman chutkan, 1 mark hamrick, 3 maryka bhattacharyya, 1 puttur d.
Asn188, asn196 hsvct2, however the role of nglycosylation in transporter function is unexplored. Svct1 sodiumdependent vitamin c transporter 1 slc23a1. Sodium dependent vitamin c transporter 1 proteins the absorption of vitamin c into the body and its distribution to organs requires two sodium dependent vitamin c transporters. The encoded protein is active in bulk vitamin c transport involving epithelial surfaces. Browse our sodium dependent vitamin c transporter 1 proteins. Prasad b ibrahim zakhary d matthew bowser c carlos isales a vadivel. Publication ascorbicacid transporter slc23a1 is essential. Mechanism of vitamin c transport, in both reduced aa openi. Genetic variation in sodiumdependent vitamin c transporters. Flavonoid inhibition of sodiumdependent vitamin c transporter 1 svct1 and glucose transporter isoform 2 glut2, intestinal transporters for vitamin c and glucose. Human intestine expresses two sodium dependent vitamin c transporters hsvct 1 and 2 that mediate cellular aa transport, with hsvct1 targeting to the apical membrane of polarized epithelia. Sodiumdependent ascorbic acid transporter family slc23. Glyoxalate reductasehydroxypyruvate reductase interacts. Vitamin c transporter slc23a1 links renal reabsorption.
Vitamin c ascorbic acid aa is essential for the synthesis of collagen and also acts as an antioxidant in the intervertebral disc ivd. We found impaired myelination and reduced collagen expression in sodium. Slc23 family of ascorbic acid transporters transporters iuphar. Sodium dependent multivitamin transporter listed as smvt. The absorption of vitamin c into the body and its distribution to organs requires two sodiumdependent vitamin c transporters. Activity of a sodiumdependent vitamin c transporter svct. Svcts are surface glycoproteins encoded by two different genes, very similar in structure. Expression and function in bone marrow stromal cells and in osteogenesis author links open overlay panel sadanand fulzele a paresh chothe b rajnikumar sangani a norman chutkan a mark hamrick c maryka bhattacharyya a puttur d.
T cells were activated in vitro in the absence or presence of vitamin c, before or after activation. Using immunohistochemistry, immunoblotting, and reverse transcription pcr, we could show that svct1 and. The intestinal fructose transporter glut5 and the intestinal sodiumdependent glucose transporter sglt1 were not inhibited by quercetin. In dorsal root ganglion drg explant cultures, hypo. Prasad b, ibrahim zakhary d, matthew bowser c, carlos isales a, vadivel ganapathy b a department of orthopaedic. In our previous study, we reported that vitamin c is transported into bmscs and bone with the help of the sodium dependent vitamin c transporter 2 svct2 fulzele et al 20.
Jci vitamin c transporter slc23a1 links renal reabsorption. Ascorbic acid aa accumulation in intestinal epithelial cells is an active. Vitamin b5 pantothenate metabolism reactome panthothenate vitamin b5 is the precursor of coenzyme a robishaw and neely 1985 and is the prosthetic group of acyl carrier protein acp joshi et al. Pdf flavonoid inhibition of sodiumdependent vitamin c. Ascorbic acid aa is required for normal human health and development. This gene encodes one of the two required transporters. Active transport requires the use of energy to drive it and in this case vitamin c passes through a sodium dependent vitamin c transporter channel. Basal sodiumdependent vitamin c transporter 2 polarization in choroid plexus explant cells in normal or scorbutic conditions skip to. Slc19 family of vitamin transporters c unless otherwise stated all data on this page refer to the human proteins. Hence, we studied the expression and activity of sodium.
Vitamin c consumed in the diet is absorbed in the small intestine via active transport by the vitamin c transporter type 1, which is a sodiumdependent transporter encoded by the solute carrier family 23, member 1 slc23a1 gene. Vitamin c is accumulated in mammalian cells by two types of proteins. Sodiumdependent vitamin c transporter 2 svct2 is necessary for the uptake of lascorbic acid into. Vitamin c is actively accumulated into the epidermal and dermal cells via the two sodiumdependent vitamin c transporter isoforms 1 and 2, suggesting that the vitamin has crucial functions in the skin. Ascorbic acid transported by sodiumdependent vitamin c. Sodium dependent vitamin c transporter 1 svct1 anticorps. The dehydroascorbic acid transporters are members of the glut family of facilitative glucose transporters. Slc23a1 gene genecards s23a1 protein s23a1 antibody.
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