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Sodium taurocholate cotransporting polypeptide

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https://www.readbyqxmd.com/read/28915572/down-regulation-of-ntcp-expression-by-cyclin-d1-in-hepatitis-b-virus-related-hepatocellular-carcinoma-has-clinical-significance
#1
Jingting Kang, Jie Wang, Jin Cheng, Zhiliang Cao, Ran Chen, Huiyu Li, Shuang Liu, Xiangmei Chen, Jianhua Sui, Fengmin Lu
The sodium-dependent taurocholate cotransporter polypeptide (NTCP) has been identified as a liver specific functional receptor for the hepatitis B virus (HBV). Previous studies indicated that the expression of NTCP may be associated with the proliferation status of hepatocytes. However, the involvement of NTCP in hepatocellular carcinoma (HCC) cells proliferation remains unclear. In this study, we confirmed that NTCP was down-regulated in HCC tumor tissues compared with that in the adjacent non-tumor tissues (P < 0...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28852124/oxidative-stress-and-immune-responses-during-hepatitis-c-virus-infection-in-tupaia-belangeri
#2
Mohammad Enamul Hoque Kayesh, Sayeh Ezzikouri, Takahiro Sanada, Haiying Chi, Yukiko Hayashi, Khadija Rebbani, Bouchra Kitab, Aya Matsuu, Noriaki Miyoshi, Tsunekazu Hishima, Michinori Kohara, Kyoko Tsukiyama-Kohara
Hepatitis C virus (HCV) is a leading cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma. To address the molecular basis of HCV pathogenesis using tupaias (Tupaia belangeri), we characterized host responses upon HCV infection. Adult tupaias were infected with HCV genotypes 1a, 1b, 2a, or 4a. Viral RNA, alanine aminotransferase, anti-HCV core and anti-nonstructural protein NS3 antibody titres, reactive oxygen species (ROS), and anti-3β-hydroxysterol-Δ24reductase (DHCR24) antibody levels were measured at 2-week intervals from 0 to 41 weeks postinfection...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28835676/homozygous-p-ser267phe-in-slc10a1-is-associated-with-a-new-type-of-hypercholanemia-and-implications-for-personalized-medicine
#3
Ruihong Liu, Chuming Chen, Xuefeng Xia, Qijun Liao, Qiong Wang, Paul J Newcombe, Shuhua Xu, Minghui Chen, Yue Ding, Xiaoying Li, Zhihong Liao, Fucheng Li, Minlian Du, Huaiqiu Huang, Ruimin Dong, Weiping Deng, Ye Wang, Binghui Zeng, Qihao Pan, Danhua Jiang, Hao Zeng, Pak Sham, Yingnan Cao, Patrick H Maxwell, Zhi-Liang Gao, Liang Peng, Yiming Wang
SLC10A1 codes for the sodium-taurocholate cotransporting polypeptide (NTCP), which is a hepatocellular transporter for bile acids (BAs) and the receptor for hepatitis B and D viruses. NTCP is also a target of multiple drugs. We aimed to evaluate the medical consequences of the loss of function mutation p.Ser267Phe in SLC10A1. We identified eight individuals with homozygous p.Ser267Phe mutation in SLC10A1 and followed up for 8-90 months. We compared their total serum BAs and 6 species of BAs with 170 wild-type and 107 heterozygous healthy individuals...
August 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28802063/hepatitis-b-virus-pregenomic-rna-in-hepatocellular-carcinoma-a-nosological-and-prognostic-determinant
#4
Boris Halgand, Christophe Desterke, Lise Rivière, Guillaume Fallot, Mylène Sebagh, Julien Calderaro, Paulette Bioulac-Sage, Christine Neuveut, Marie-Annick Buendia, Didier Samuel, Cyrille Féray
Hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma (HCC). However, very little is known about the replication of HBV in HCC tissues. PATIENTS AND METHODS: We analysed viral and cellular parameters in HCC (T) and non-tumor liver (NT) samples from 99 HBsAg-positive, virologically suppressed patients treated by tumour resection or liver transplantation. We examined total HBV DNA and RNA as well as covalently closed circular DNA (cccDNA) and pregenomic RNA (pgRNA), which are considered as markers of active HBV replication...
August 12, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28717041/activation-of-sting-in-hepatocytes-suppresses-the-replication-of-hepatitis-b-virus
#5
Fang Guo, Liudi Tang, Sainan Shu, Mohit Sehgal, Muhammad Sheraz, Bowei Liu, Qiong Zhao, Junjun Cheng, Xuesen Zhao, Tianlun Zhou, Jinhong Chang, Ju-Tao Guo
Induction of interferon and proinflammatory cytokines is a hallmark of the infection of many different viruses. However, hepatitis B virus (HBV) does not elicit a detectable cytokine response in infected hepatocytes. In order to investigate the molecular mechanism underlying the innate immune evasion, a functional cGAS-STING pathway was reconstituted in a human hepatoma cell line supporting tetracycline-inducible HBV replication. It was demonstrated that induction of HBV replication neither activated nor inhibited this cytosolic DNA sensing pathway...
July 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28624460/identification-of-kx2-391-as-an-inhibitor-of-hbv-transcription-by-a-recombinant-hbv-based-screening-assay
#6
Keisuke Harada, Hironori Nishitsuji, Saneyuki Ujino, Kunitada Shimotohno
Antiviral therapies for chronic hepatitis B virus (HBV) infection that are currently applicable for clinical use are limited to nucleos(t)ide analogs targeting HBV polymerase activity and pegylated interferon alpha (PEG-IFN). Towards establishing an effective therapy for HBV related diseases, it is important to develop a new anti-HBV agent that suppresses and eradicates HBV. This study used recombinant HBV encoding NanoLuc to screen anti-HBV compounds from 1827 US Food and Drug Administration approved compounds and identified several compounds that suppressed HBV infection...
August 2017: Antiviral Research
https://www.readbyqxmd.com/read/28559272/an-effective-antiviral-approach-targeting-hepatitis-b-virus-with-njk14047-a-novel-and-selective-biphenyl-amide-p38-mitogen-activated-protein-kinase-inhibitor
#7
So-Young Kim, Hong Kim, Sang-Won Kim, Na-Rae Lee, Chae-Min Yi, Jinyuk Heo, Bum-Joon Kim, Nam-Jung Kim, Kyung-Soo Inn
Despite recent advances in therapeutic strategies against hepatitis B virus (HBV) infection, chronic hepatitis B remains a major global health burden. Recent studies have shown that targeting host factors instead of viral factors can be an effective antiviral strategy with low risk of the development of resistance. Efforts to identify host factors affecting viral replication have identified p38 mitogen-activated protein kinase (MAPK) as a possible target for antiviral strategies against various viruses, including HBV...
August 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28551415/interferon-%C3%AE-response-is-impaired-by-hepatitis-b-virus-infection-in-tupaia-belangeri
#8
Mohammad Enamul Hoque Kayesh, Sayeh Ezzikouri, Haiying Chi, Takahiro Sanada, Naoki Yamamoto, Bouchra Kitab, Takumi Haraguchi, Rika Matsuyama, Chimène Nze Nkogue, Hitoshi Hatai, Noriaki Miyoshi, Shuko Murakami, Yasuhito Tanaka, Jun-Ichiro Takano, Yumiko Shiogama, Yasuhiro Yasutomi, Michinori Kohara, Kyoko Tsukiyama-Kohara
To date, the chimpanzee has been used as the natural infection model for hepatitis B virus (HBV). However, as this model is very costly and difficult to use because of ethical and animal welfare issues, we aimed to establish the tupaia (Tupaia belangeri) as a new model for HBV infection and characterized its intrahepatic innate immune response upon HBV infection. First, we compared the propagation of HBV genotypes A2 and C in vivo in tupaia hepatocytes. At 8-10days post infection (dpi), the level of HBV-A2 propagation in the tupaia liver was found to be higher than that of HBV-C...
May 25, 2017: Virus Research
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
#9
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/28374759/human-induced-pluripotent-stem-cell-derived-hepatocyte-like-cells-as-an-in-vitro-model-of-human-hepatitis-b-virus-infection
#10
Fuminori Sakurai, Seiji Mitani, Tatsuro Yamamoto, Kazuo Takayama, Masashi Tachibana, Koichi Watashi, Takaji Wakita, Sayuki Iijima, Yasuhito Tanaka, Hiroyuki Mizuguchi
In order to understand the life cycle of hepatitis B virus (HBV) and to develop efficient anti-HBV drugs, a useful in vitro cell culture system which allows HBV infection and recapitulates virus-host interactions is essential; however, pre-existing in vitro HBV infection models are often problematic. Here, we examined the potential of human induced-pluripotent stem (iPS) cell-derived hepatocyte-like cells (iPS-HLCs) as an in vitro HBV infection model. Expression levels of several genes involved in HBV infection, including the sodium taurocholate cotransporting polypeptide (NTCP) gene, were gradually elevated as the differentiation status of human iPS cells proceeded to iPS-HLCs...
April 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28357379/hepatitis-b-virus-and-its-sexually-transmitted-infection-an-update
#11
REVIEW
Takako Inoue, Yasuhito Tanaka
incidence and prevalence: About 5% of the world's population has chronic hepatitis B virus (HBV) infection, and nearly 25% of carriers develop chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The prevalence of chronic HBV infection in human immunodeficiency virus (HIV)-infected individuals is 5%-15%; HIV/HBV coinfected individuals have a higher level of HBV replication, with higher rates of chronicity, reactivation, occult infection, and HCC than individuals with HBV only. The prevalence of HBV genotype A is significantly higher among men who have sex with men (MSM), compared with the rest of the population...
September 5, 2016: Microbial Cell
https://www.readbyqxmd.com/read/28302211/-sodium-taurocholate-cotransporting-polypeptide-deficiency-manifesting-as-cholestatic-jaundice-in-early-infancy-a-complicated-case-study
#12
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/28249291/bile-acid-uptake-transporters-as-targets-for-therapy
#13
REVIEW
Davor Slijepcevic, Stan F J van de Graaf
Bile acids are potent signaling molecules that regulate glucose, lipid and energy homeostasis predominantly via the bile acid receptors farnesoid X receptor (FXR) and transmembrane G protein-coupled receptor 5 (TGR5). The sodium taurocholate cotransporting polypeptide (NTCP) and the apical sodium dependent bile acid transporter (ASBT) ensure an effective circulation of (conjugated) bile acids. The modulation of these transport proteins affects bile acid localization, dynamics and signaling. The NTCP-specific pharmacological inhibitor myrcludex B inhibits hepatic uptake of conjugated bile acids...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28249278/mechanisms-of-tauroursodeoxycholate-mediated-hepatoprotection
#14
REVIEW
Dieter Häussinger, Claus Kordes
Ursodeoxycholate and its taurine conjugate tauroursodeoxycholate (TUDC) promote choleresis by triggering the insertion of transport proteins for bile acids into the canalicular and basolateral membranes of hepatocytes. In addition, TUDC exerts hepatoprotective and anti-apoptotic effects, can counteract the action of toxic bile acids and reduce endoplasmic reticulum stress. TUDC can also initiate the differentiation of multipotent mesenchymal stem cells (MSC) including hepatic stellate cells and promote their development into hepatocyte-like cells...
2017: Digestive Diseases
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
#15
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/28237774/identification-of-urine-tauro-%C3%AE-muricholic-acid-as-a-promising-biomarker-in-polygoni-multiflori-radix-induced-hepatotoxicity-by-targeted-metabolomics-of-bile-acids
#16
Dong-Sheng Zhao, Li-Long Jiang, Ya-Xi Fan, Lei-Chi Dong, Jiang Ma, Xin Dong, Xiao-Jun Xu, Ping Li, Hui-Jun Li
Polygoni Multiflori Radix (PMR) has been widely used as a tonic for centuries. However, hepatotoxicity cases linked to PMR have been frequently reported and appropriate biomarkers for clinical diagnosis are currently lacking. Here, an approach using UPLC-QqQ/MS-based targeted metabolomics of bile acids (BAs) complemented with biochemistry and histopathology was applied to characterize the development and recovery processes of PMR-induced hepatotoxicity in rats and to identify biomarkers. The expression of bile salt export pump (Bsep) and sodium taurocholate cotransporting polypeptide (Ntcp) were evaluated to investigate the underlying mechanism...
February 24, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28213271/woodchuck-sodium-taurocholate-cotransporting-polypeptide-supports-low-level-hepatitis-b-and-d-virus-entry
#17
Liran Fu, Hongjie Hu, Yang Liu, Zhiyi Jing, Wenhui Li
Sodium taurocholate cotransporting polypeptide (NTCP) is the functional receptor for human hepatitis B virus (HBV) and its satellite hepatitis D virus (HDV). Species barriers to HBV/HDV infection are mainly determined at entry level by variations in the sequences of particular NTCP orthologs. In this study, we sought to determine whether the NTCP ortholog in woodchuck (Marmota monax), woodchuck NTCP (wNTCP) supports viral infection. We found that wNTCP is capable of supporting HBV/HDV infection in HepG2 cells, but to much lower extent than human NTCP (hNTCP), which is about 90% reduction of hNTCP...
May 2017: Virology
https://www.readbyqxmd.com/read/28195359/sodium-taurocholate-cotransporting-polypeptide-is-the-limiting-host-factor-of-hepatitis-b-virus-infection-in-macaque-and-pig-hepatocytes
#18
Florian A Lempp, Ellen Wiedtke, Bingqian Qu, Pierre Roques, Isabelle Chemin, Florian W R Vondran, Roger Le Grand, Dirk Grimm, Stephan Urban
Infections with the human hepatitis B virus (HBV) and hepatitis D virus (HDV) depend on species-specific host factors like the receptor human sodium taurocholate cotransporting polypeptide (hNTCP). Complementation of mouse hepatocytes with hNTCP confers susceptibility to HDV but not HBV, indicating the requirement of additional HBV-specific factors. As an essential premise toward the establishment of an HBV-susceptible animal model, we investigated the role of hNTCP as a limiting factor of hepatocytes in commonly used laboratory animals...
February 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver 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
#19
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/28125599/n-glycosylation-of-the-na-taurocholate-cotransporting-polypeptide-ntcp-determines-its-trafficking-and-stability-and-is-required-for-hepatitis-b-virus-infection
#20
Monique D Appelman, Anindita Chakraborty, Ulrike Protzer, Jane A McKeating, Stan F J van de Graaf
The sodium/bile acid cotransporter NTCP was recently identified as a receptor for hepatitis B virus (HBV). NTCP is glycosylated and the role of glycans in protein trafficking or viral receptor activity is not known. NTCP contains two N-linked glycosylation sites and asparagine amino acid residues N5 and N11 were mutated to a glutamine to generate NTCP with a single glycan (NTCP-N5Q or NTCP- N11Q) or no glycans (NTCP- N5,11Q). HepG2 cells expressing NTCP with a single glycan supported HBV infection at a comparable level to NTCP-WT...
2017: PloS One
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