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Sodium taurocholate cotransporting polypeptide

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https://www.readbyqxmd.com/read/29730285/a-new-strategy-to-identify-hepatitis-b-virus-entry-inhibitors-by-alphascreen-technology-targeting-the-envelope-receptor-interaction
#1
Wakana Saso, Senko Tsukuda, Hirofumi Ohashi, Kento Fukano, Ryo Morishita, Satoko Matsunaga, Mio Ohki, Akihide Ryo, Sam-Yong Park, Ryosuke Suzuki, Hideki Aizaki, Masamichi Muramatsu, Camille Sureau, Takaji Wakita, Tetsuro Matano, Koichi Watashi
Current anti-hepatitis B virus (HBV) agents have limited effect in curing HBV infection, and thus novel anti-HBV agents with different modes of action are in demand. In this study, we applied AlphaScreen assay to high-throughput screening of small molecules inhibiting the interaction between HBV large surface antigen (LHBs) and the HBV entry receptor, sodium taurocholate cotransporting polypeptide (NTCP). From the chemical screening, we identified that rapamycin, an immunosuppressant, strongly inhibited the LHBs-NTCP interaction...
May 3, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29723527/inhibitory-effect-of-fasiglifam-on-hepatitis-b-virus-infections-through-suppression-of-the-sodium-taurocholate-cotransporting-polypeptide
#2
Yasunori Nio, Yuichi Akahori, Hitomi Okamura, Koichi Watashi, Takaji Wakita, Makoto Hijikata
Fasiglifam is a selective partial agonist of G-protein-coupled receptor 40 (GPR40), which was developed for the treatment of type 2 diabetes mellitus. However, the clinical development of fasiglifam was voluntarily terminated during phase III clinical trials due to adverse liver effects. Fasiglifam showed an inhibitory effect on sodium taurocholate cotransporting polypeptide (NTCP) in human and rat hepatocytes. Recently, NTCP was reported to be a functional receptor for human hepatitis B virus (HBV) infections...
April 30, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29658451/-clinical-and-genetic-analysis-of-a-pediatric-patient-with-sodium-taurocholate-cotransporting-polypeptide-deficiency
#3
Hua Li, Jian-Wu Qiu, Gui-Zhi Lin, Mei Deng, Wei-Xia Lin, Ying Cheng, Yuan-Zong Song
Sodium taurocholate cotransporting polypeptide (NTCP) deficiency is an inborn error of bile acid metabolism caused by mutations of SLC10A1 gene. This paper reports the clinical and genetic features of a patient with this disease. A 3.3-month-old male infant was referred to the hospital with the complaint of jaundiced skin and sclera over 3 months. Physical examination revealed moderate jaundice of the skin and sclera. The liver was palpable 3.5 cm below the right subcostal margin with a medium texture. Serum biochemistry analysis revealed markedly elevated bilirubin (predominantly direct bilirubin) and total bile acids (TBA), as well as decreased 25-OH-VitD level...
April 2018: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/29456407/analysis-of-hepatitis-b-virus-pres1-variability-and-prevalence-of-the-rs2296651-polymorphism-in-a-spanish-population
#4
Rosario Casillas, David Tabernero, Josep Gregori, Irene Belmonte, Maria Francesca Cortese, Carolina González, Mar Riveiro-Barciela, Rosa Maria López, Josep Quer, Rafael Esteban, Maria Buti, Francisco Rodríguez-Frías
AIM: To determine the variability/conservation of the domain of hepatitis B virus (HBV) preS1 region that interacts with sodium-taurocholate cotransporting polypeptide (hereafter, NTCP-interacting domain) and the prevalence of the rs2296651 polymorphism (S267F, NTCP variant) in a Spanish population. METHODS: Serum samples from 246 individuals were included and divided into 3 groups: patients with chronic HBV infection (CHB) ( n = 41, 73% Caucasians), patients with resolved HBV infection ( n = 100, 100% Caucasians) and an HBV-uninfected control group ( n = 105, 100% Caucasians)...
February 14, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29426822/chemical-array-system-a-platform-to-identify-novel-hepatitis-b-virus-entry-inhibitors-targeting-sodium-taurocholate-cotransporting-polypeptide
#5
Manabu Kaneko, Yushi Futamura, Senko Tsukuda, Yasumitsu Kondoh, Tomomi Sekine, Hiroyuki Hirano, Kento Fukano, Hirofumi Ohashi, Wakana Saso, Ryo Morishita, Satoko Matsunaga, Fumihiro Kawai, Akihide Ryo, Sam-Yong Park, Ryosuke Suzuki, Hideki Aizaki, Naoko Ohtani, Camille Sureau, Takaji Wakita, Hiroyuki Osada, Koichi Watashi
Current anti-hepatitis B virus (HBV) agents including interferons and nucleos(t)ide analogs efficiently suppress HBV infection. However, as it is difficult to eliminate HBV from chronically infected liver, alternative anti-HBV agents targeting a new molecule are urgently needed. In this study, we applied a chemical array to high throughput screening of small molecules that interacted with sodium taurocholate cotransporting polypeptide (NTCP), an entry receptor for HBV. From approximately 30,000 compounds, we identified 74 candidates for NTCP interactants, and five out of these were shown to inhibit HBV infection in cell culture...
February 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29290974/sodium-taurocholate-cotransporting-polypeptide-ntcp-deficiency-identification-of-a-novel-slc10a1-mutation-in-two-unrelated-infants-presenting-with-neonatal-indirect-hyperbilirubinemia-and-remarkable-hypercholanemia
#6
Jian-Wu Qiu, Mei Deng, Ying Cheng, Raza-Muhammad Atif, Wei-Xia Lin, Li Guo, Hua Li, Yuan-Zong Song
Sodium taurocholate cotransporting polypeptide (NTCP) is encoded by the gene SLC10A1 and expressed in the basolateral membrane of the hepatocyte, functioning to uptake bile acids from plasma. Although SLC10A1 has been cloned and NTCP function studied intensively for years, clinical description of NTCP deficiency remains rather limited. This study reported the genotypic and phenotypic features of two neonatal patients with NTCP deficiency. They both presented with neonatal indirect hyperbilirubinemia and remarkable hypercholanemia, and harbored the SLC10A1 variants c...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29285260/genetic-variations-of-ntcp-are-associated-with-susceptibility-to-hbv-infection-and-related-hepatocellular-carcinoma
#7
Peng Wang, Ruidong Mo, Rongtao Lai, Yumin Xu, Jie Lu, Gangde Zhao, Yuhan Liu, Zhujun Cao, Xiaolin Wang, Ziqiang Li, Lanyi Lin, Huijuan Zhou, Wei Cai, Hui Wang, Shisan Bao, Xiaogang Xiang, Qing Xie
Sodium taurocholate cotransporting polypeptide (NTCP), encoded by gene SLC10A1, is a receptor for hepatitis B virus (HBV). The aim of the current study was to investigate the role of NTCP polymorphisms in HBV susceptibility, cirrhosis and hepatocarcinogenesis. A total 1221 cases [including 866 chronic hepatitis B (CHB), 238 liver cirrhosis (LC), 117 hepatocellular carcinoma (HCC) patients] and 1232 healthy controls (HCs) were recruited, and 6 single nucleotide polymorphisms (SNPs) were genotyped. Meta-analysis was executed among 14591 CHBs and 12396 HCs to determine the association between NTCP polymorphisms and HBV infection, cirrhosis or hepatocarcinogenesis...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29247233/effect-of-s267f-variant-of-ntcp-on-the-patients-with-chronic-hepatitis-b
#8
Hye Won Lee, Hye Jung Park, Bora Jin, Mehrangiz Dezhbord, Do Young Kim, Kwang-Hyub Han, Wang-Shick Ryu, Seungtaek Kim, Sang Hoon Ahn
Sodium taurocholate cotransporting polypeptide (NTCP) was identified as an entry receptor for hepatitis B virus (HBV) infection. The substitution of serine at position 267 of NTCP with phenylalanine (S267F) is an Asian-specific variation that hampers HBV entry in vitro. In this study, we aimed to evaluate the prevalence of S267F polymorphism in Korean patients with chronic hepatitis B (CHB) and its association with disease progression and potential viral evolution in the preS1 domain of HBV. We found that the frequency of the S267F variant of NTCP in CHB patients and controls was 2...
December 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29247188/hepatocytic-expression-of-human-sodium-taurocholate-cotransporting-polypeptide-enables-hepatitis-b-virus-infection-of-macaques
#9
Benjamin J Burwitz, Jochen M Wettengel, Martin A Mück-Häusl, Marc Ringelhan, Chunkyu Ko, Marvin M Festag, Katherine B Hammond, Mina Northrup, Benjamin N Bimber, Thomas Jacob, Jason S Reed, Reed Norris, Byung Park, Sven Moller-Tank, Knud Esser, Justin M Greene, Helen L Wu, Shaheed Abdulhaqq, Gabriela Webb, William F Sutton, Alex Klug, Tonya Swanson, Alfred W Legasse, Tania Q Vu, Aravind Asokan, Nancy L Haigwood, Ulrike Protzer, Jonah B Sacha
Hepatitis B virus (HBV) is a major global health concern, and the development of curative therapeutics is urgently needed. Such efforts are impeded by the lack of a physiologically relevant, pre-clinical animal model of HBV infection. Here, we report that expression of the HBV entry receptor, human sodium-taurocholate cotransporting polypeptide (hNTCP), on macaque primary hepatocytes facilitates HBV infection in vitro, where all replicative intermediates including covalently closed circular DNA (cccDNA) are present...
December 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/29217749/hepatitis-delta-virus-persists-during-liver-regeneration-and-is-amplified-through-cell-division-both-in-vitro-and-in-vivo
#10
Katja Giersch, Oliver D Bhadra, Tassilo Volz, Lena Allweiss, Kristoffer Riecken, Boris Fehse, Ansgar W Lohse, Joerg Petersen, Camille Sureau, Stephan Urban, Maura Dandri, Marc Lütgehetmann
OBJECTIVE: Hepatitis delta virus (HDV) was shown to persist for weeks in the absence of HBV and for months after liver transplantation, demonstrating the ability of HDV to persevere in quiescent hepatocytes. The aim of the study was to evaluate the impact of cell proliferation on HDV persistence in vitro and in vivo. DESIGN: Genetically labelled human sodium taurocholate cotransporting polypeptide (hNTCP)-transduced human hepatoma(HepG2) cells were infected with HBV/HDV and passaged every 7 days for 100 days in the presence of the entry inhibitor Myrcludex-B...
December 7, 2017: Gut
https://www.readbyqxmd.com/read/29216213/a-multi-scale-spatial-model-of-hepatitis-b-viral-dynamics
#11
Quentin Cangelosi, Shawn A Means, Harvey Ho
Chronic hepatitis B viral infection (HBV) afflicts around 250 million individuals globally and few options for treatment exist. Once infected, the virus entrenches itself in the liver with a notoriously resilient colonisation of viral DNA (covalently-closed circular DNA, cccDNA). The majority of infections are cleared, yet we do not understand why 5% of adult immune responses fail leading to the chronic state with its collateral morbid effects such as cirrhosis and eventual hepatic carcinoma. The liver environment exhibits particularly complex spatial structures for metabolic processing and corresponding distributions of nutrients and transporters that may influence successful HBV entrenchment...
2017: PloS One
https://www.readbyqxmd.com/read/29192196/a-robust-cell-culture-system-supporting-the-complete-life-cycle-of-hepatitis-b-virus
#12
Eleftherios Michailidis, Jonathan Pabon, Kuanhui Xiang, Paul Park, Vyas Ramanan, Hans-Heinrich Hoffmann, William M Schneider, Sangeeta N Bhatia, Ype P de Jong, Amir Shlomai, Charles M Rice
The discovery of sodium taurocholate cotransporting polypeptide (NTCP) as the hepatitis B virus (HBV) receptor enabled researchers to create hepatoma cell lines susceptible to HBV infection. Infection in current systems, however, is inefficient and virus fails to spread. Infection efficiency is enhanced by treating cells with polyethylene glycol 8000 (PEG) during infection. However, this alone does not promote virus spread. Here we show that maintaining PEG in culture medium increases the rate of infection by at least one order of magnitude, and, most importantly, promotes virus spread...
November 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29089529/heparin-at-physiological-concentration-can-enhance-peg-free-in-vitro-infection-with-human-hepatitis-b-virus
#13
Gansukh Choijilsuren, Ren-Shiang Jhou, Shu-Fan Chou, Ching-Jen Chang, Hwai-I Yang, Yang-Yuan Chen, Wan-Long Chuang, Ming-Lung Yu, Chiaho Shih
Hepatitis B virus (HBV) is a blood-borne pathogen responsible for chronic hepatitis, cirrhosis, and liver cancer. The mechanism of HBV entry into hepatocytes remains to be investigated. Recently, sodium taurocholate cotransporting polypeptide (NTCP) was discovered as a major HBV receptor based on an in vitro infection system using NTCP-reconstituted HepG2 cells. However, this infection system relies on the compound polyethylene glycol (4% PEG), which is not physiologically relevant to human infection. High concentration of heparin has been commonly used as an inhibitor control for in vitro infection in the field...
October 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28962642/upregulation-of-sodium-taurocholate-cotransporter-polypeptide-during-hepatogenic-differentiation-of-umbilical-cord-matrix-mesenchymal-stem-cells-facilitates-hepatitis-b-entry
#14
Camillo Sargiacomo, Hoda El-Kehdy, Kai Dallmeier, Joery de Kock, Clara Hernandez-Kelly, Vera Rogiers, Arturo Ortega, Johan Neyts, Etienne Sokal, Mustapha Najimi
BACKGROUND: Hepatitis B virus (HBV) carriers worldwide number approximately 240 million people and around 780,000 people die every year from HBV infection. HBV entry and uptake are functionally linked to the presence of the human sodium-taurocholate cotransporting peptide (hNTCP) receptor. Recently, our group demonstrated that human umbilical cord matrix stem cells (UCMSCs) become susceptible to HBV after in-vitro hepatogenic differentiation (D-UCMSCs). METHODS: In the present study, we examined the involvement of hNTCP in governing D-UCMSC susceptibility to HBV infection by characterizing the modulation of this transporter expression during hepatogenic differentiation and by appreciating the inhibition of its activity on infection efficacy...
September 29, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28949917/a-potent-human-neutralizing-antibody-fc-dependently-reduces-established-hbv-infections
#15
Dan Li, Wenhui He, Ximing Liu, Sanduo Zheng, Yonghe Qi, Huiyu Li, Fengfeng Mao, Juan Liu, Yinyan Sun, Lijing Pan, Kaixin Du, Keqiong Ye, Wenhui Li, Jianhua Sui
Hepatitis B virus (HBV) infection is a major global health problem. Currently-available therapies are ineffective in curing chronic HBV infection. HBV and its satellite hepatitis D virus (HDV) infect hepatocytes via binding of the preS1 domain of its large envelope protein to sodium taurocholate cotransporting polypeptide (NTCP). Here, we developed novel human monoclonal antibodies that block the engagement of preS1 with NTCP and neutralize HBV and HDV with high potency. One antibody, 2H5-A14, functions at picomolar level and exhibited neutralization-activity-mediated prophylactic effects...
September 26, 2017: ELife
https://www.readbyqxmd.com/read/28915572/down-regulation-of-ntcp-expression-by-cyclin-d1-in-hepatitis-b-virus-related-hepatocellular-carcinoma-has-clinical-significance
#16
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
#17
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
#18
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
#19
COMPARATIVE STUDY
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. We analyzed viral and cellular parameters in HCC (T) and nontumor liver (NT) samples from 99 hepatitis B surface antigen (HBsAg)-positive, virologically suppressed patients treated by tumor 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...
January 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28717041/activation-of-stimulator-of-interferon-genes-in-hepatocytes-suppresses-the-replication-of-hepatitis-b-virus
#20
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 cyclic GMP-AMP (cGAMP) synthase (cGAS)-stimulator of interferon genes (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...
October 2017: Antimicrobial Agents and Chemotherapy
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