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SLC10A1

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https://www.readbyqxmd.com/read/28794147/erratum-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
#1
https://www.readbyqxmd.com/read/28725001/2-3-7-8-tetrachlorodibenzo-p-dioxin-tcdd-elicited-effects-on-bile-acid-homeostasis-alterations-in-biosynthesis-enterohepatic-circulation-and-microbial-metabolism
#2
Kelly A Fader, Rance Nault, Chen Zhang, Kazuyoshi Kumagai, Jack R Harkema, Timothy R Zacharewski
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant which elicits hepatotoxicity through activation of the aryl hydrocarbon receptor (AhR). Male C57BL/6 mice orally gavaged with TCDD (0.01-30 µg/kg) every 4 days for 28 days exhibited bile duct proliferation and pericholangitis. Mass spectrometry analysis detected a 4.6-fold increase in total hepatic bile acid levels, despite the coordinated repression of genes involved in cholesterol and primary bile acid biosynthesis including Cyp7a1...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28543042/the-ntcp-inhibitor-myrcludex-b-effects-on-bile-acid-disposition-and-tenofovir-pharmacokinetics
#3
A Blank, A Eidam, M Haag, N Hohmann, J Burhenne, M Schwab, Sfj van de Graaf, M R Meyer, H H Maurer, K Meier, J Weiss, T Bruckner, A Alexandrov, S Urban, G Mikus, W E Haefeli
Myrcludex B acts as a hepatitis B and D virus entry inhibitor blocking the sodium taurocholate cotransporting polypeptide (SLC10A1). We investigated the effects of myrcludex B on plasma bile acid disposition, tenofovir pharmacokinetics, and perpetrator characteristics on cytochrome P450 (CYP) 3A. Twelve healthy volunteers received 300 mg tenofovir disoproxil fumarate orally and 10 mg subcutaneous myrcludex B. Myrcludex B increased total plasma bile acid exposure 19.2-fold without signs of cholestasis. The rise in conjugated bile acids was up to 124-fold (taurocholic acid)...
May 24, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28498614/hepatic-uptake-of-conjugated-bile-acids-is-mediated-by-both-ntcp-and-oatps-and-modulated-by-intestinal-sensing-of-plasma-bile-acid-levels-in-mice
#4
Davor Slijepcevic, Reinout L P Roscam Abbing, Takeshi Katafuchi, Antje Blank, Joanne M Donkers, Stéphanie van Hoppe, Dirk R de Waart, Dagmar Tolenaars, Jonathan H M van der Meer, Manon Wildenberg, Ulrich Beuers, Ronald P J Oude Elferink, Alfred H Schinkel, Stan F J van de Graaf
BACKGROUND & AIMS: The Na(+) -taurocholate cotransporting polypeptide (NTCP/SLC10A1) is believed to be pivotal for hepatic uptake of conjugated bile acids. However, plasma bile acid levels are normal in a subset of NTCP knockout mice and in mice treated with myrcludex B, a specific NTCP inhibitor. Here, we elucidated which transport proteins mediate the hepatic uptake of conjugated bile acids and demonstrated intestinal sensing of elevated bile acid levels in plasma in mice. METHODS: Mice or healthy volunteers were treated with myrcludex B...
May 12, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28429786/comprehensive-assessment-showed-no-associations-of-variants-at-the-slc10a1-locus-with-susceptibility-to-persistent-hbv-infection-among-southern-chinese
#5
Ying Zhang, Yuanfeng Li, Miantao Wu, Pengbo Cao, Xiaomin Liu, Qian Ren, Yun Zhai, Bobo Xie, Yanling Hu, Zhibin Hu, Jinxin Bei, Jie Ping, Xinyi Liu, Yinghua Yu, Bingqian Guo, Hui Lu, Guanjun Liu, Haitao Zhang, Ying Cui, Zengnan Mo, Hongbing Shen, Yi-Xin Zeng, Fuchu He, Hongxing Zhang, Gangqiao Zhou
The sodium taurocholate cotransporting polypeptide (NTCP) encoded by SLC10A1 was recently demonstrated to be a functional receptor for hepatitis B virus (HBV). The role of SLC10A1 polymorphisms, particularly the Ser267Phe variant (rs2296651) in exon 4, has been frequently investigated in regard to risk of persistent HBV infection. However, these investigations have generated conflicting results. To examine whether common genetic variation at the SLC10A1 locus is associated with risk of persistent HBV infection, haplotype-tagging and imputed single nucleotide polymorphisms (SNPs) were assessed in two case-control sample sets, totally including 2,550 cases (persistently HBV infected subjects, PIs) and 2,124 controls (spontaneously recovered subjects, SRs) of Southern Chinese ancestry...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28302211/-sodium-taurocholate-cotransporting-polypeptide-deficiency-manifesting-as-cholestatic-jaundice-in-early-infancy-a-complicated-case-study
#6
Yuan-Zong Song, Mei Deng
Sodium taurocholate cotransporting polypeptide (NTCP) deficiency is caused by SLC10A1 mutations impairing the NTCP function to uptake plasma bile salts into the hepatocyte. Thus far, patients with NTCP deficiency were rarely reported. The patient in this paper was a 5-month-19-day male infant with the complaint of jaundiced skin and sclera for 5.5 months as well as abnormal liver function revealed over 4 months. His jaundice was noticed on the second day after birth, and remained visible till his age of 1 month and 13 days, when a liver function test unveiled markedly elevated total, direct and indirect bilirubin as well as total bile acids (TBA)...
March 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28249272/extended-abstract-deficiency-of-sodium-taurocholate-cotransporting-polypeptide-slc10a1-a-new-inborn-error-of-metabolism-with-an-attenuated-phenotype
#7
Frédéric M Vaz, Hidde H Huidekoper, Coen C Paulusma
We present the first patient with a defect in the Na+-taurocholate cotransporting polypeptide SLC10A1 (NTCP), which plays a key role in the enterohepatic circulation of bile salts. The clinical presentation of the child was mild and the child showed no signs of liver dysfunction or pruritus despite extremely elevated plasma bile salt levels (>100-fold upper-limit of normal). A homozygous point mutation was found in the SLC10A1 gene (resulting in amino acid change R252H) and functional studies confirmed the pathogenicity of the mutation...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28125961/lack-of-ser267phe-variant-of-sodium-taurocholate-cotransporting-polypeptide-among-moroccans-regardless-of-hepatitis-b-virus-infection-status
#8
Sayeh Ezzikouri, Hajar Chihab, Abdellah Elhabazi, Lahcen Wakrim, Soumaya Benjelloun
BACKGROUND: The sodium taurocholate co-transporting polypeptide, encoded by SLC10A1, was identified as a functional receptor for hepatitis B virus (HBV). The objective of this study was to determine if there was an association of the Ser267Phe variant (rs2296651) with HBV infection status in Moroccan patients. METHODS: Using a TaqMan 5' allelic discrimination assay, the Ser267Phe variant was genotyped in 286 chronic hepatitis B patients, 135 individuals with spontaneous clearance from HBV infection and 109 healthy controls negative for hepatitis B serological markers...
January 26, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28077388/na-taurocholate-cotransporting-polypeptide-ntcp-slc10a1-ortholog-in-the-marine-skate-leucoraja-erinacea-is-not-a-physiological-bile-salt-transporter
#9
Dongke Yu, Han Zhang, Daniel A Lionarons, James L Boyer, Shi-Ying Cai
The Na(+)-dependent taurocholate cotransporting polypeptide (NTCP/SLC10A1) is a hepatocyte-specific solute carrier, which plays an important role in maintaining bile salt homeostasis in mammals. The absence of a hepatic Na(+)-dependent bile salt transport system in marine skate and rainbow trout raises a question regarding the function of the Slc10a1 gene in these species. Here, we have characterized the Slc10a1 gene in the marine skate, Leucoraja erinacea The transcript of skate Slc10a1 (skSlc10a1) encodes 319 amino acids and shares 46% identity to human NTCP (hNTCP) with similar topology to mammalian NTCP...
April 1, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/27882152/clinical-and-molecular-study-of-a-pediatric-patient-with-sodium-taurocholate-cotransporting-polypeptide-deficiency
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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