SVCT2 _ SLC23A2 Control Peptide antibody _CP
- Known as:
- SVCT2 _ SLC23A2 Control Peptide (anti-) _CP
- Catalog number:
- 'AP18200CP-N
- Product Quantity:
- 0.1 mg
- Category:
- -
- Supplier:
- ACR
- Gene target:
- SVCT2 _ SLC23A2 Control Peptide antibody _CP
Related genes to: SVCT2 _ SLC23A2 Control Peptide antibody _CP
- Gene:
- SLC23A1 NIH gene
- Name:
- solute carrier family 23 member 1
- Previous symbol:
- SLC23A2
- Synonyms:
- YSPL3, SVCT1
- Chromosome:
- 5q31.2
- Locus Type:
- gene with protein product
- Date approved:
- 1998-10-23
- Date modifiied:
- 2016-02-17
- Gene:
- SLC23A2 NIH gene
- Name:
- solute carrier family 23 member 2
- Previous symbol:
- SLC23A1
- Synonyms:
- SVCT2, KIAA0238, YSPL2
- Chromosome:
- 20p13
- Locus Type:
- gene with protein product
- Date approved:
- 1999-08-13
- Date modifiied:
- 2016-02-17
Related products to: SVCT2 _ SLC23A2 Control Peptide antibody _CP
Related articles to: SVCT2 _ SLC23A2 Control Peptide antibody _CP
- The anti-tumor effect of high-dose ascorbic acid (AA) has been demonstrated in multiple and cancer models with the postulation of two primary categories of mechanisms: antioxidant/cofactor activity and H O -mediated oxidative damage. Both mechanisms have been conclusively demonstrated . However, while parenteral high-dose AA-induced cofactor activity (TET-mediated DNA demethylation and prolyl/asparaginyl hydroxylase-mediated HIF activity inhibition via reduction of enzymatic Fe to Fe ) has been demonstrated intratumorally in multiple models, the cumulative data on parenteral high-dose AA-induced intratumoral oxidative damage has been inconclusive. Furthermore, the relative contribution of the seemingly opposing mechanisms towards anti-cancer activity has not been studied concurrently. We therefore sought to definitively delineate the roles of both antioxidant/cofactor activity and prooxidant functions of high-dose AA in the anti-tumor response. Using two syngeneic mouse tumor models, the AA-sensitive A20 model and the AA-resistant Renca model, we assessed markers of DNA and lipid oxidative damage as well as the specific roles of TET2 and AA transporter SLC23A2 in the anti-tumor response to parenteral high-dose AA. In the sensitive A20 model, loss of either or fully reversed anti-tumor activity. Similarly, overexpression of in the resistant Renca model (which expresses high baseline levels of AA transporters SLC23A1 and SLC23A2, but does not express TET2), resulted in increased CD8 T cell infiltration and dramatic reduction in tumor growth overall. In both A20 and Renca models, high-dose parenteral AA total intratumoral antioxidant capacity, and this was attenuated by knockdown in A20. High-dose AA treatment also resulted in a - and -dependent increase in intratumoral 5-hydroxymethylcytosine. Intracellular oxidative damage markers, 8-OHdG and 4-HNE, were not induced in tumors by high-dose AA in either model. In contrast, these markers were robustly induced by high-dose AA in A20 and Renca cells. Using dynamic real-time extracellular H O measurements with high-dose AA, difference in molecular oxygen concentration between standard and hypoxic conditions was identified as an important factor underlying the marked discrepancy between the abundant and absent intratumoral oxidative stress with high-dose AA. Furthermore, using additional syngeneic models resistant (MB49) and sensitive (MC38) to AA-induced potentiation of anti-PD1 checkpoint inhibition, we demonstrate that very low catalase expression does not confer sensitivity to high-dose AA (further arguing against the H O mechanism ), that TET2 expression alone is not sufficient to drive an AA-induced anti-tumor response (either as a single agent or in combination with immunotherapy), and that high-dose AA can significantly enhance the efficacy of anti-PD1 immunotherapy even in the absence of single-agent activity. Our data strongly indicate that the anti-tumor effect of high-dose parenteral AA-including potentiation of immunotherapy-is mediated primarily by its specific antioxidant/cofactor activity (with TET2 expression likely being necessary but certainly not sufficient), and not via oxidative stress. Collectively, the study represents a paradigm shift in our understanding of the cumulative mechanisms of anti-cancer activity of high-dose AA, with critical implications not just for the clinical translation of AA as an anti-cancer agent (including in enhancing immunotherapy efficacy) but also the field of free radical biology. - Source: PubMed
Publication date: 2025/05/24
Akram TaliaLuchtel Rebecca ADubey VinaySeal SomaAggarwal RiteshSai HiroakiShenoy Niraj K - Humans and other primates lack the ability to synthesize the essential nutrient, Vitamin C, which is derived exclusively from the diet. Crucial for effective vitamin C uptake are the Na dependent Vitamin C transporters, SVCT1 and SVCT2, members of the nucleobase ascorbate transporter (NAT) family. SVCT1 and 2 actively transport the reduced form of Vitamin C, ascorbic acid, into key tissues. The recent structure of the mouse SVCT1 revealed the molecular basis of substrate binding and that, like the other structurally characterised members of the NAT family, it exists as a closely associated dimer. SVCT1 is likely to function via the elevator mechanism with the core domain of each protomer able to bind substrate and move through the membrane carrying the substrate across the membrane. Here we explored the function of a range of variants of the human SVCT1, revealing a range of residues involved in substrate selection and binding, and confirming the importance of the C-terminus in membrane localisation. Furthermore, using a dominant negative mutant we show that the dimer is essential for transport function, as previously seen in the fungal homologue, UapA. In addition, we show that a localisation deficient C-terminal truncation of SVCT1 blocks correct localisation of co-expressed, associated wildtype SVCT1. These results clearly show the importance of the dimer in both correct SVCT1 trafficking and transport activity. - Source: PubMed
Publication date: 2024/10/04
Woubshete MenebereChan Lok IDiallinas GeorgeByrne Bernadette - The active DNA demethylation process, which involves TET proteins, can affect DNA methylation pattern. TET dependent demethylation results in DNA hypomethylation by oxidation 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) and its derivatives. Moreover, TETs' activity may be upregulated by ascorbate. Given that aberrant DNA methylation of genes implicated in breast carcinogenesis may be involved in tumor progression, we wanted to determine whether breast cancer patients exert changes in the active DNA demethylation process. The study included blood samples from breast cancer patients (n = 74) and healthy subjects (n = 71). We analyzed the expression of genes involved in the active demethylation process (qRT-PCR), and 5-mC and its derivatives level (2D-UPLC MS/MS). The ascorbate level was determined using UPLC-MS. Breast cancer patients had significantly higher TET3 expression level, lower 5-mC and 5-hmC DNA levels. TET3 was significantly increased in luminal B breast cancer patients with expression of hormone receptors. Moreover, the ascorbate level in the plasma of breast cancer patients was decreased with the accompanying increase of sodium-dependent vitamin C transporters (SLC23A1 and SLC23A2). The presented study indicates the role of TET3 in DNA demethylation in breast carcinogenesis. - Source: PubMed
Publication date: 2024/03/18
Linowiecka KingaGuz JolantaDziaman TomaszUrbanowska-Domańska OlgaZarakowska EwelinaSzpila AnnaSzpotan JustynaSkalska-Bugała AleksandraMijewski PawełSiomek-Górecka AgnieszkaRóżalski RafałGackowski DanielOliński RyszardFoksiński Marek - Solute carrier family 23 member 1 (SVCT1) and solute carrier family 23 member 2 (SVCT2), encoded by SLC23A1 and SLC23A2, may be associated with preeclampsia (PE). The purpose of this study was to investigate the association between polymorphisms of SLC23A1 and SLC23A2 and PE in Chinese Han population. The primers and double-labeled probes were designed according to the SNPs of rs10063949 in SLC23A1, rs6133175 and rs1279683 in SLC23A2. Genomic DNA was extracted from peripheral blood of 2,066 subjects (1,029 with PE and 1,037 without PE), and Taqman real-time PCR was used to detect the three SNPs. We observed a significant difference in genotypic frequency of the SLC23A2 rs6133175 polymorphism (χ=8.08, p=0.02) between PE patients and controls, while no significant differences were found in the allelic frequencies (χ=1.45, p=0.23). Then we fractionized these samples into the dominant model of the allele G (GG/AG+AA group) or the recessive model of the A allele (AA/AG+GG group), and observed a significant difference under the recessive model of the A allele (p=0.01, OR=0.71, 95% CI 0.55-0.92). Furthermore, there were no significant differences in the genotypic and allelic frequencies of rs10063949 and rs1279683 between PE patients and controls (for rs10063949, χ=2.96, p=0.23 by genotype, χ=2.11, p=0.15 by allele; for rs1279683, χ=1.52, p=0.47 by genotype, χ=0.64, p=0.44 by allele). We first found that SLC23A2 rs6133175 may be the certain genetic polymorphisms modulating their effects in the development of PE in a Chinese Han population and the AG or GG genotypes may be a risk factor for PE. - Source: PubMed
Hou HuabinZhang YongjieWu HongjingHuang ZuzhouLiu ShiguoLiang HuiXu Yinglei - Apolipoprotein E E4 (APOE4) is a risk factor for cognitive decline. A high blood vitamin C (VC) level reduces APOE4-associated risk of developing cognitive decline in women. In the present study, we aimed to examine the effects of functional variants of VC transporter genes expressed in the brain (SLC2A1, SLC2A3, and SLC23A2) on APOE4-associated risk of developing cognitive decline. This case-control study involved 393 Japanese subjects: 252 cognitively normal and 141 cognitively impaired individuals (87 mild cognitive impairment and 54 dementia). Database searches revealed that rs1279683 of SLC23A2, and rs710218 and rs841851 of SLC2A1 are functional variants that are significantly associated with the altered expression of the respective genes and genotyped as three single nucleotide variants (SNVs). When stratified by SNV genotype, we found a significant association between APOE4 and cognitive decline in minor allele carriers of rs1279683 (odds ratio [OR] 2.02, 95% CI, 1.05-3.87, p = 0.035) but not in the homozygote carriers of the major allele. Significant associations between APOE4 and cognitive decline were also observed in participants with major allele homozygotes of rs710218 (OR 2.35, 95% CI, 1.05-5.23, p = 0.037) and rs841851 (OR 3.2, 95% CI, 1.58-6.46, p = 0.0012), but not in minor allele carriers of the respective SNVs. In contrast, the three functional SNVs showed no significant effect on cognitive decline. Our results imply that functional SNVs of VC transporter genes can affect APOE4-associated risk of developing cognitive decline via altered VC levels in the brain. - Source: PubMed
Publication date: 2021/11/15
Hayashi KojiNoguchi-Shinohara MoekoSato TakehiroHosomichi KazuyoshiKannon TakayukiAbe ChiemiDomoto ChiakiYuki-Nozaki SohshiMori AyakaHorimoto MaiYokogawa MasamiSakai KenjiIwasa KazuoKomai KiyonobuIshimiya MaiNakamura HiroyukiIshida NatsukoSuga YukioIshizaki JunkoIshigami AkihitoTajima AtsushiYamada Masahito