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SLC10A1

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https://www.readbyqxmd.com/read/27882152/clinical-and-molecular-study-of-a-pediatric-patient-with-sodium-taurocholate-cotransporting-polypeptide-deficiency
#1
Mei Deng, Man Mao, Li Guo, Feng-Ping Chen, Wang-Rong Wen, Yuan-Zong Song
The human solute carrier family 10 member 1 (SLC10A1) gene encodes sodium taurocholate cotransporting polypeptide (NTCP), the principal transporter of conjugated bile salts from the plasma into hepatocytes. Although the function of NTCP has been studied extensively and a number of SLC10A1 variations have been identified in humans, information regarding NTCP deficiency is limited. To date, only one patient with NTCP deficiency has been described; however, in the present study a pediatric patient who experienced intractable and striking hypercholanemia is presented...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27743010/influence-of-testosterone-on-phase-ii-metabolism-and-availability-of-soy-isoflavones-in-male-wistar-rats
#2
Sebastian T Soukup, Dennis R Müller, Anne Kurrat, Patrick Diel, Sabine E Kulling
Genistein and daidzein are the main isoflavones in soy. Their potential beneficial or adverse effects in males like the prevention of prostate cancer or the impact on reproductive functions are controversially discussed. Major determinants of their bioactivity are the absorption and biotransformation of isoflavones. In this study, we focused on the influence of testosterone on plasma availability and phase II metabolism of isoflavones. Male Wistar rats, receiving an isoflavones rich diet, were randomized into three groups: Two groups were orchiectomized (ORX) at postnatal day (PND) 80 and treated for 11 days with testosterone propionate (TP) (ORX TP group) or a vehicle (ORX group) after a 7 days lasting hormonal decline...
October 14, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27569060/mapping-the-cell-surface-n-glycoproteome-of-human-hepatocytes-reveals-markers-for-selecting-a-homogeneous-population-of-ipsc-derived-hepatocytes
#3
Sunil K Mallanna, Max A Cayo, Kirk Twaroski, Rebekah L Gundry, Stephen A Duncan
When comparing hepatic phenotypes between iPSC-derived hepatocyte-like cells from different liver disease patients, cell heterogeneity can confound interpretation. We proposed that homogeneous cell populations could be generated by fluorescence-activated cell sorting (FACS). Using cell-surface capture proteomics, we identified a total of 300 glycoproteins on hepatocytes. Analyses of the expression profiles during the differentiation of iPSCs revealed that SLC10A1, CLRN3, and AADAC were highly enriched during the final stages of hepatocyte differentiation...
September 13, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27491457/genetic-variants-in-the-regulatory-region-of-slc10a1-are-not-associated-with-the-risk-of-hepatitis-b-virus-infection-and-clearance
#4
Xueqin Chen, Ying Wang, Xiaohua Chen, Kailiang Cheng, Jiaoyuan Li, Jiao Lou, Juntao Ke, Yang Yang, Yajie Gong, Ying Zhu, Li Wang, Rong Zhong
The Na/taurocholate cotransporter NTCP (encoded by SLC10A1) was identified as a cellular entry receptor for the human hepatitis B virus (HBV), advancing our understanding of the molecular mechanism of HBV infection. An alternative hypothesis was put forward that regulatory variants in SLC10A1 might play an important role in HBV susceptibility by potentially influencing expression levels of NTCP. The three regulatory SNPs (rs8011311, rs7154439, rs111409076) were genotyped in 1023 HBV-persistent carriers, 735 subjects with HBV natural clearance and 732 HBV marker-negative subjects in a Han Chinese population...
October 2016: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/27440443/transcriptome-analyses-of-inner-cell-mass-and-trophectoderm-cells-isolated-by-magnetic-activated-cell-sorting-from-bovine-blastocysts-using-single-cell-rna-seq
#5
X-M Zhao, L-S Cui, H-S Hao, H-Y Wang, S-J Zhao, W-H Du, D Wang, Y Liu, H-B Zhu
Research on bovine embryonic stem cells (bESCs) has been hampered because bESCs are cultured in conditions that are based on information obtained from culturing mouse and human inner cell mass (ICM) cells. The aim of this study was to compare gene expression in ICM and trophectoderm (TE) cell lineages of bovine embryos and to discuss the findings relative to information available for mice and humans. We separated a high-purity (>90%) ICM and TE from bovine blastocysts by magnetic-activated cell sorting and analysed their transcriptomes by single cell RNA-seq...
October 2016: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/27212637/genetic-variant-in-cxcl13-gene-is-associated-with-susceptibility-to-intrauterine-infection-of-hepatitis-b-virus
#6
Zhihua Wan, Xiaofang Lin, Tongyang Li, Aifen Zhou, Mei Yang, Dan Hu, Li Feng, Songxu Peng, Linlin Fan, Si Tu, Bin Zhang, Yukai Du
Intrauterine infection of hepatitis B virus (HBV), which accounts for the majority of mother-to-child transmission, is one of the main reasons for the failure of combined immunoprophylaxis against the transmission. Recent studies have identified that genetic background might influence the susceptibility to intrauterine infection of HBV. We conducted this study to investigate the associations between 10 genetic variants in 9 genes (SLC10A1, HLA-DP, HLA-C, CXCR5, CXCL13, TLR3, TLR4, TLR9 and UBE2L3) of mothers and their neonates and HBV intrauterine infection...
2016: Scientific Reports
https://www.readbyqxmd.com/read/26977098/endotoxin-mediated-downregulation-of-hepatic-drug-transporters-in-hiv-1-transgenic-rats
#7
Ragia H Ghoneim, Micheline Piquette-Miller
Altered expression of drug transporters and metabolic enzymes is known to occur in infection-induced inflammation. We hypothesize that in human immunodeficiency virus (HIV)-infected individuals, further alteration could occur as a result of augmented inflammation. The HIV-1 transgenic (Tg) rat is used to simulate HIV pathologies associated with the presence of HIV viral proteins. Therefore, the objective of this study was to examine the effect of endotoxin administration on the gene expression of drug transporters in the liver of HIV-Tg rats...
May 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/26642861/the-rs2296651-s267f-variant-on-ntcp-slc10a1-is-inversely-associated-with-chronic-hepatitis-b-and-progression-to-cirrhosis-and-hepatocellular-carcinoma-in-patients-with-chronic-hepatitis-b
#8
Hui-Han Hu, Jessica Liu, Yu-Ling Lin, Wun-Sheng Luo, Yu-Ju Chu, Chia-Lin Chang, Chin-Lan Jen, Mei-Hsuan Lee, Sheng-Nan Lu, Li-Yu Wang, San-Lin You, Hwai-I Yang, Chien-Jen Chen
OBJECTIVE: The sodium taurocholate co-transporting polypeptide (NTCP), encoded by SLC10A1, was recently identified as a receptor for HBV. We assessed the association of the p.Ser267Phe variant (rs2296651) with chronic hepatitis B (CHB) serostatus, cirrhosis and hepatocellular carcinoma (HCC) in patients with CHB. DESIGN: The variant was genotyped in 3801 patients with CHB and 3801 matched hepatitis B surface antigen (HBsAg) seronegative individuals. ORs with 95% CIs for the variant's association with CHB, cirrhosis and HCC were estimated using logistic regression...
September 2016: Gut
https://www.readbyqxmd.com/read/26627605/hsp90-and-hepatobiliary-transformation-during-sea-lamprey-metamorphosis
#9
Yu-Wen Chung-Davidson, Chu-Yin Yeh, Ugo Bussy, Ke Li, Peter J Davidson, Kaben G Nanlohy, C Titus Brown, Steven Whyard, Weiming Li
BACKGROUND: Biliary atresia (BA) is a human infant disease with inflammatory fibrous obstructions in the bile ducts and is the most common cause for pediatric liver transplantation. In contrast, the sea lamprey undergoes developmental BA with transient cholestasis and fibrosis during metamorphosis, but emerges as a fecund adult. Therefore, sea lamprey liver metamorphosis may serve as an etiological model for human BA and provide pivotal information for hepatobiliary transformation and possible therapeutics...
December 1, 2015: BMC Developmental Biology
https://www.readbyqxmd.com/read/26382575/effect-of-common-polymorphisms-of-the-farnesoid-x-receptor-and-bile-acid-transporters-on-the-pharmacokinetics-of-ursodeoxycholic-acid
#10
Miao Hu, Benny S P Fok, Siu-Kwan Wo, Vincent H L Lee, Zhong Zuo, Brian Tomlinson
Ursodeoxycholic acid (UDCA), a natural, dihydroxy bile acid, promotes gallstone dissolution and has been attributed with several other beneficial effects. The farnesoid X receptor (FXR) may influence the pharmacokinetics of UDCA by modulating the expression of bile acid transporters. This exploratory study examined whether common functional polymorphisms in FXR and in bile acid transporter genes affect the pharmacokinetics of exogenous UDCA. Polymorphisms in genes for transporters involved in bile acid transport, solute carrier organic anion 1B1 (SLCO1B1) 388A>G and 521T>C, solute carrier 10A1 (SLC10A1) 800 C>T and ATP-binding cassette B11 (ABCB11) 1331T>C, and the FXR -1G>T polymorphism were genotyped in 26 male Chinese subjects who ingested single oral 500-mg doses of UDCA...
January 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/26272151/analysis-of-sinusoidal-drug-uptake-transporter-activities-in-primary-human-hepatocytes
#11
Marc Le Vée, Elodie Jouan, Claire Denizot, Yannick Parmentier, Olivier Fardel
Hepatic drug transporters play an important role in pharmacokinetics and drug-drug interactions. Among these membrane transporters, the sodium taurocholate cotransporting polypeptide (NTCP/SLC10A1), the organic anion transporting polypeptides (OATPs) 1B1 (SLCO1B1), 1B3 (SLCO1B3) and 2B1 (SLCO2B1), the organic anion transporter 2 (OAT2/SLC22A7) and the organic cation transporter 1 (OCT1/SLC22A1) are likely major ones, notably mediating sinusoidal uptake of various drugs or endogenous compounds, like bile acids, from blood into hepatocytes...
2015: Methods in Molecular Biology
https://www.readbyqxmd.com/read/26084360/expression-sorting-and-transport-studies-for-the-orphan-carrier-slc10a4-in-neuronal-and-non-neuronal-cell-lines-and-in-xenopus-laevis-oocytes
#12
Stephanie Schmidt, Marcela Moncada, Simone Burger, Joachim Geyer
BACKGROUND: SLC10A4 belongs to the solute carrier family SLC10 whose founding members are the Na(+)/taurocholate co-transporting polypeptide (NTCP, SLC10A1) and the apical sodium-dependent bile acid transporter (ASBT, SLC10A2). These carriers maintain the enterohepatic circulation of bile acids between the liver and the gut. SLC10A4 was identified as a novel member of the SLC10 carrier family with the highest phylogenetic relationship to NTCP. The SLC10A4 protein was detected in synaptic vesicles of cholinergic and monoaminergic neurons of the peripheral and central nervous system, suggesting a transport function for any kind of neurotransmitter...
June 19, 2015: BMC Neuroscience
https://www.readbyqxmd.com/read/26071008/ntcp-opens-the-door-for-hepatitis-b-virus-infection
#13
REVIEW
Huan Yan, Yang Liu, Jianhua Sui, Wenhui Li
A liver bile acids transporter, sodium taurocholate cotransporting polypeptide (NTCP, encoded by SLC10A1) was recently identified as a functional receptor for hepatitis B virus (HBV) and its satellite hepatitis D virus (HDV). NTCP-complemented human hepatoma HepG2 cells (HepG2-NTCP) were shown to support infection of HBV and HDV in vitro, providing a much-needed and convenient cell culture system for the viruses. Identification of NTCP as a functional receptor for HBV has significantly advanced our understanding of the viral life cycle and opened new opportunities for developing anti-HBV interventions...
September 2015: Antiviral Research
https://www.readbyqxmd.com/read/25886055/the-inhibition-of-hepatic-bile-acids-transporters-ntcp-and-bsep-is-involved-in-the-pathogenesis-of-isoniazid-rifampicin-induced-hepatotoxicity
#14
Yao Xue Guo, Xue Fei Xu, Qi Zhi Zhang, Chun Li, Ye Deng, Pei Jiang, Lei Yan He, Wen Xing Peng
Co-treatment of isoniazid (INH) and rifampicin (RFP) is well known for clinically apparent liver injury. However, the mechanism of INH/RFP-induced liver injury is controversial. Emerging evidence shows links between inhibition of bile acids transporters and drug-induced liver injury (DILI). The present study investigates whether sodium taurocholate cotransporting polypeptide (NTCP/Ntcp; SLC10A1) and bile salt export pump (BSEP/Bsep; ABCB11) are involved in the anti-tuberculosis medicines induced liver injury...
2015: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/25651692/bile-canalicular-changes-and-defective-bile-secretion-in-opisthorchis-viverrini-infected-hamsters
#15
Lakhanawan Charoensuk, Porntip Pinlaor, Umawadee Laothong, Puangrat Yongvanit, Chawalit Pairojkul, Yukifumi Nawa, Somchai Pinlaor
Infection with the liver fluke Opisthorchis viverrini (Digenea) (Poirier, 1886) causes bile duct injury and periductal fibrosis by chronic overproduction of inflammatory-mediators and eventually results in cholangiocarcinoma development. While extensive research works have been done on O. viverrini infection-associated changes of bile ducts and periductal fibrosis, little attention was paid on morphological and biochemical changes of the bile canaliculi (BC), the origin of bile flow. We aimed to investigate the morphological and functional alterations of BC in the liver of hamsters infected with O...
December 2014: Folia Parasitologica
https://www.readbyqxmd.com/read/25498879/association-of-polymorphisms-in-drug-transporter-genes-slco1b1-and-slc10a1-and-anti-tuberculosis-drug-induced-hepatotoxicity-in-a-chinese-cohort
#16
RANDOMIZED CONTROLLED TRIAL
Ru Chen, Jing Wang, Shaowen Tang, Yuan Zhang, Xiaozhen Lv, Shanshan Wu, Yinyin Xia, Peiyuan Deng, Yu Ma, Dehua Tu, Dafang Chen, Siyan Zhan
This study investigated the association between genetic variants in two hepatic uptake transporter genes (SLCO1B1 and SLC10A1) and the risk of anti-tuberculosis drug-induced hepatotoxicity (ATDH) in a Chinese cohort. The frequencies and distributions of single nucleotide polymorphisms (SNPs) and haplotypes of these genes were compared among 89 incident ATDH cases and 356 matched ATDH-free controls using a multivariate conditional logistic regression analysis. After correction for potential confounding factors, significant differences were found in polymorphism of rs4149014 under an addictive model (P = 0...
January 2015: Tuberculosis
https://www.readbyqxmd.com/read/25481222/interaction-of-human-organic-anion-transporter-2-oat2-and-sodium-taurocholate-cotransporting-polypeptide-ntcp-with-antineoplastic-drugs
#17
Venkata V V R Marada, Saskia Flörl, Annett Kühne, Judith Müller, Gerhard Burckhardt, Yohannes Hagos
The ability of an antineoplastic drug to exert its cytostatic effect depends largely on the balance between its uptake into and extrusion from the cancer cells. ATP driven efflux transporter proteins drive the export of antineoplastic drugs and play a pivotal role in the development of chemoresistance. As regards uptake transporters, comparably less is known on their impact in drug action. In the current study, we characterized the interactions of two uptake transporter proteins, expressed mainly in the liver; the organic anion transporter 2 (OAT2, encoded by the SLC22A7 gene) and the sodium taurocholate cotransporting polypeptide (NTCP, encoded by the SLC10A1 gene), stably transfected in human embryonic kidney cells, with some antineoplastic agents that are routinely being used in cancer chemotherapy...
January 2015: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/25418280/the-p-ser267phe-variant-in-slc10a1-is-associated-with-resistance-to-chronic-hepatitis-b
#18
Liang Peng, Qiang Zhao, Qibin Li, Miaoxin Li, Caixia Li, Tingting Xu, Xiangyi Jing, Xiang Zhu, Ye Wang, Fucheng Li, Ruihong Liu, Cheng Zhong, Qihao Pan, Binghui Zeng, Qijun Liao, Bin Hu, Zhao-xia Hu, Yang-su Huang, Pak Sham, Jinsong Liu, Shuhua Xu, Jun Wang, Zhi-liang Gao, Yiming Wang
UNLABELLED: In the past 50 years there have been considerable efforts to identify the cellular receptor of hepatitis B virus (HBV). Recently, in vitro evidence from several groups has shown that the sodium-taurocholate cotransporting polypeptide (NTCP, which is encoded by SLC10A1 and transports bile acids into hepatic cells in enterohepatic recirculation) is a strong candidate. In particular, in vitro the p.Ser267Phe variation of SLC10A1 results in loss of HBV receptor function. We tested the role of NTCP as a receptor for HBV in chronic hepatitis B patients using a genetic association study...
April 2015: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/25219859/synthesis-and-in-vitro-evaluation-of-bile-acid-prodrugs-of-floxuridine-to-target-the-liver
#19
Diana Vivian, James E Polli
Floxuridine is often used to treat metastatic liver disease and is given as an infusion directly into the hepatic artery to increase the amount of intact drug that reaches the liver. The objective of this work was to design and synthesize prodrugs of floxuridine through conjugation to chenodeoxycholic acid (CDCA) to target the liver via the bile acid liver uptake transporter Na(+)/taurocholate cotransporting polypeptide (NTCP, SLC10A1). Two isomeric prodrugs of floxuridine were synthesized: floxuridine 3'glutamic acid-CDCA and floxuridine 5'-glutamic acid-CDCA...
November 20, 2014: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/25193235/ntcp-deficiency-a-new-inherited-disease-of-bile-acid-transport
#20
COMMENT
Serge Erlinger
The authors report the case of a child with extreme elevation of serum bile acid concentration, without pruritus, symptomatic cholestasis, liver disease, or abnormalities of liver function tests. Sequencing of the SLC10A1 gene, encoding NTCP (the sinusoidal uptake transporter of conjugated bile acids) revealed a single homozygous point mutation in the coding sequence of the gene resulting in an arginine to histidine substitution at position 252. This mutation resulted in a markedly reduced uptake activity of taurocholic acid...
February 2015: Clinics and Research in Hepatology and Gastroenterology
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