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Sodium taurocholate cotransporting polypeptide

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https://www.readbyqxmd.com/read/27890789/cyclosporin-derivatives-inhibit-hepatitis-b-virus-entry-without-interfering-the-ntcp-transporter
#1
Satomi Shimura, Koichi Watashi, Kento Fukano, Michael Peel, Ann Sluder, Fumihiro Kawai, Masashi Iwamoto, Senko Tsukuda, Junko S Takeuchi, Takeshi Miyake, Masaya Sugiyama, Yuki Ogasawara, Sam-Yong Park, Yasuhito Tanaka, Hiroyuki Kusuhara, Masashi Mizokami, Camille Sureau, Takaji Wakita
BACKGROUND&AIMS: Most of the specific inhibitors of hepatitis B virus (HBV) entry, including myrcludex-B and cyclosporin A (CsA), target an HBV entry receptor, sodium taurocholate cotransporting polypeptide (NTCP). As all these agents have capacities to impair the NTCP transporter activity for bile acid uptake and thus may cause significant adverse effects, we aim to identify small molecules that inhibit HBV entry but least affecting the NTCP transporter function. METHODS: We focused on derivatives of CsA, which originally inhibited both HBV entry and NTCP-mediated bile acid uptake, to analyze the possibility to distinguish these two activities...
November 24, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27882152/clinical-and-molecular-study-of-a-pediatric-patient-with-sodium-taurocholate-cotransporting-polypeptide-deficiency
#2
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/27863453/a-new-class-of-hepatitis-b-and-d-virus-entry-inhibitors-proanthocyanidin-and-its-analogs-that-directly-act-on-the-viral-large-surface-proteins
#3
Senko Tsukuda, Koichi Watashi, Taichi Hojima, Masanori Isogawa, Masashi Iwamoto, Katsumi Omagari, Ryosuke Suzuki, Hideki Aizaki, Soichi Kojima, Masaya Sugiyama, Akiko Saito, Yasuhito Tanaka, Masashi Mizokami, Camille Sureau, Takaji Wakita
: Introduction of direct acting antivirals against hepatitis C virus (HCV) has provided a revolutionary improvement in the treatment outcome. In contrast to HCV, however, the strategy for developing new antiviral agents against hepatitis B virus (HBV), especially viral-targeting compounds, is limited since HBV requires only four viral genes for its efficient replication/infection. Here, we identify an oligomeric flavonoid, proanthocyanidin (PAC) and its analogs, which inhibit HBV entry into host cells by targeting the HBV large surface protein (LHBs)...
November 18, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27827798/unimpaired-immunogenicity-of-yeast-expressed-hepatitis-b-surface-antigen-stored-at-elevated-temperatures
#4
Zhongliang Shen, Yuliang Rao, Shuai Tao, Mengjun Luo, Lijun Ming, Jing Liu, Shaokun Pan, Youhua Xie
Global adoption of hepatitis B virus (HBV) vaccines has greatly reduced new HBV infections. Current HBV vaccines are liquid suspensions containing recombinant hepatitis B surface antigen (HBsAg) particles mixed with aluminum phosphate or aluminum hydroxide. Refrigeration (2-8°C) as recommended for vaccine transport and storage may be unachievable in certain HBV-prevalent developing countries or regions. In this study, we stored yeast-expressed HBsAg and aluminum hydroxide separately at the standard (4°C) and elevated temperature (25, 37, or 45°C) for 14, 23, and 30 days, then mixed them and used the mixture to vaccinate mice with a prime-boost program...
November 8, 2016: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/27784961/elucidation-of-the-early-infection-machinery-of-hepatitis-b-virus-by-using-bio-nanocapsule
#5
REVIEW
Qiushi Liu, Masaharu Somiya, Shun'ichi Kuroda
Currently, hepatitis B virus (HBV), upon attaching to human hepatocytes, is considered to interact first with heparan sulfate proteoglycan (HSPG) via an antigenic loop of HBV envelope S protein. Then, it is promptly transferred to the sodium taurocholate cotransporting polypeptide (NTCP) via the myristoylated N-terminal sequence of pre-S1 region (from Gly-2 to Gly-48, HBV genotype D), and it finally enters the cell by endocytosis. However, it is not clear how HSPG passes HBV to NTCP and how NTCP contributes to the cellular entry of HBV...
October 14, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27783675/dna-polymerase-%C3%AE%C2%BA-is-a-key-cellular-factor-for-the-formation-of-covalently-closed-circular-dna-of-hepatitis-b-virus
#6
Yonghe Qi, Zhenchao Gao, Guangwei Xu, Bo Peng, Chenxuan Liu, Huan Yan, Qiyan Yao, Guoliang Sun, Yang Liu, Dingbin Tang, Zilin Song, Wenhui He, Yinyan Sun, Ju-Tao Guo, Wenhui Li
Hepatitis B virus (HBV) infection of hepatocytes begins by binding to its cellular receptor sodium taurocholate cotransporting polypeptide (NTCP), followed by the internalization of viral nucleocapsid into the cytoplasm. The viral relaxed circular (rc) DNA genome in nucleocapsid is transported into the nucleus and converted into covalently closed circular (ccc) DNA to serve as a viral persistence reservoir that is refractory to current antiviral therapies. Host DNA repair enzymes have been speculated to catalyze the conversion of rcDNA to cccDNA, however, the DNA polymerase(s) that fills the gap in the plus strand of rcDNA remains to be determined...
October 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27746336/human-stem-cell-derived-hepatocytes-as-a-model-for-hepatitis-b-virus-infection-spreading-and-virus-host-interactions
#7
Yuchen Xia, Arnaud Carpentier, Xiaoming Cheng, Peter Daniel Block, Yao Zhao, Zhensheng Zhang, Ulrike Protzer, T Jake Liang
BACKGROUND & AIMS: One major obstacle of hepatitis B virus (HBV) research is the lack of efficient cell culture system permissive for viral infection and replication. The aim of our study was to establish a robust HBV infection model by using hepatocyte-like cells (HLCs) derived from human pluripotent stem cells. METHODS: HLCs were differentiated from human embryonic stem cells and induced pluripotent stem cells. Maturation of hepatocyte functions was determined...
October 14, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27534692/hepatitis-delta-virus-insights-into-a-peculiar-pathogen-and-novel-treatment-options
#8
REVIEW
Florian A Lempp, Yi Ni, Stephan Urban
Chronic hepatitis D is the most severe form of viral hepatitis, affecting ∼20 million HBV-infected people worldwide. The causative agent, hepatitis delta virus (HDV), is a unique human pathogen: it is the smallest known virus; it depends on HBV to disseminate its viroid-like RNA; it encodes only one protein (HDAg), which has both structural and regulatory functions; and it replicates using predominantly host proteins. The failure of HBV-specific nucleoside analogues to suppress the HBV helper function, and the limitations of experimental systems to study the HDV life cycle, have impeded the development of HDV-specific drugs...
October 2016: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/27515132/inhibitory-effect-of-cdk9-inhibitor-fit-039-on-hepatitis-b-virus-propagation
#9
Tomohisa Tanaka, Kaori Okuyama-Dobashi, Shuko Murakami, Wenjia Chen, Toru Okamoto, Keiji Ueda, Takamitsu Hosoya, Yoshiharu Matsuura, Akihide Ryo, Yasuhito Tanaka, Masatoshi Hagiwara, Kohji Moriishi
Current therapies for hepatitis B virus (HBV) cannot completely eliminate the HBV genome because of the stable population of covalently closed circular DNA (cccDNA) and so on. FIT-039, which is a cyclin-dependent kinase (CDK) 9 inhibitor, is known to suppress the replication of several DNA viruses including HSV, HPV and human adenovirus. In this study, we investigated the antiviral effect of FIT-039 on HBV infection. HepG2 cells expressing human sodium taurocholate cotransporting polypeptide (HepG2/NTCP cells) were infected with HBV in the presence of FIT-039...
September 2016: Antiviral Research
https://www.readbyqxmd.com/read/27466423/modification-of-three-amino-acids-in-sodium-taurocholate-cotransporting-polypeptide-renders-mice-susceptible-to-infection-with-hepatitis-d-virus-in-vivo
#10
Wenhui He, Zhiliang Cao, Fengfeng Mao, Bijie Ren, Yunfei Li, Dan Li, Huiyu Li, Bo Peng, Huan Yan, Yonghe Qi, Yinyan Sun, Fengchao Wang, Jianhua Sui, Wenhui Li
UNLABELLED: Sodium taurocholate cotransporting polypeptide (NTCP) was identified as a functional receptor for hepatitis D virus (HDV) and its helper hepatitis B virus (HBV). In cultured cell lines, HDV infection through mouse NTCP is restricted by residues 84 to 87 of the receptor. This study shows that mice with these three amino acids altered their corresponding human residues (H84R, T86K, and S87N) in endogenous mouse NTCP support de novo HDV infection in vivo HDV infection was documented by the presence of replicative forms of HDV RNA and HDV proteins in liver cells at day 6 after viral inoculation...
October 1, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27420796/cellular-uptake-of-hepatitis-b-virus-envelope-l-particles-is-independent-of-sodium-taurocholate-cotransporting-polypeptide-but-dependent-on-heparan-sulfate-proteoglycan
#11
Masaharu Somiya, Qiushi Liu, Nobuo Yoshimoto, Masumi Iijima, Kenji Tatematsu, Tadashi Nakai, Toshihide Okajima, Kazuyuki Kuroki, Keiji Ueda, Shun'ichi Kuroda
Sodium taurocholate cotransporting polypeptide (NTCP) was recently discovered as a hepatitis B virus (HBV) receptor, however, the detailed mechanism of HBV entry is not yet fully understood. We investigated the cellular entry pathway of HBV using recombinant HBV surface antigen L protein particles (bio-nanocapsules, BNCs). After the modification of L protein in BNCs with myristoyl group, myristoylated BNCs (Myr-BNCs) were found to bind to NTCP in vitro, and inhibit in vitro HBV infection competitively, suggesting that Myr-BNCs share NTCP-dependent infection machinery with HBV...
October 2016: Virology
https://www.readbyqxmd.com/read/27406326/bile-acids-induce-necrosis-in-pancreatic-stellate-cells-dependent-on-calcium-entry-and-sodium-driven-bile-uptake
#12
Pawel E Ferdek, Monika A Jakubowska, Julia V Gerasimenko, Oleg V Gerasimenko, Ole H Petersen
Acute biliary pancreatitis, caused by bile reflux into the pancreas, is a serious condition characterised by premature activation of digestive enzymes within acinar cells, followed by necrosis and inflammation. Bile acids are known to induce pathological Ca(2+) signals and necrosis in acinar cells. However, bile acid-elicited signalling events in stellate cells remain unexplored. This is the first study to demonstrate the pathophysiological effects of bile acids on stellate cells in two experimental models: ex vivo (mouse pancreatic lobules) and in vitro (human cells)...
July 13, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27386799/human-induced-pluripotent-stem-cell-derived-hepatic-cell-lines-as-a-new-model-for-host-interaction-with-hepatitis-b-virus
#13
Shun Kaneko, Sei Kakinuma, Yasuhiro Asahina, Akihide Kamiya, Masato Miyoshi, Tomoyuki Tsunoda, Sayuri Nitta, Yu Asano, Hiroko Nagata, Satoshi Otani, Fukiko Kawai-Kitahata, Miyako Murakawa, Yasuhiro Itsui, Mina Nakagawa, Seishin Azuma, Hiromitsu Nakauchi, Hironori Nishitsuji, Saneyuki Ujino, Kunitada Shimotohno, Masashi Iwamoto, Koichi Watashi, Takaji Wakita, Mamoru Watanabe
Hepatitis B virus (HBV) is not eradicated by current antiviral therapies due to persistence of HBV covalently closed circular DNA (cccDNA) in host cells, and thus development of novel culture models for productive HBV infection is urgently needed, which will allow the study of HBV cccDNA eradication. To meet this need, we developed culture models of HBV infection using human induced pluripotent stem cell-derived hepatocyte lineages, including immature proliferating hepatic progenitor-like cell lines (iPS-HPCs) and differentiated hepatocyte-like cells (iPS-Heps)...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27384660/unusual-features-of-sodium-taurocholate-cotransporting-polypeptide-as-a-hepatitis-b-virus-receptor
#14
Jisu Li, Li Zong, Camille Sureau, Luke Barker, Jack R Wands, Shuping Tong
UNLABELLED: Cell culture (cc)-derived hepatitis B virus (HBV) can infect differentiated HepaRG cells, but efficient infection requires addition of polyethylene glycol (PEG) during inoculation. Identification of sodium taurocholate cotransporting polypeptide (NTCP) as an HBV receptor enabled ccHBV infection of NTCP reconstituted HepG2 cells, although very little hepatitis B surface antigen (HBsAg) is produced. We found infection by patient serum-derived HBV (sHBV), which required purification of viral particles through ultracentrifugation or PEG precipitation, was PEG independent and much more efficient in HepaRG cells than in HepG2/NTCP cells...
September 15, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27351278/down-regulation-of-ntcp-expression-by-cyclin-d1-in-hepatitis-b-virus-related-hepatocellular-carcinoma-has-clinical-significance
#15
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...
June 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27329181/core-fucosylation-plays-a-pivotal-role-in-hepatitis-b-pseudo-virus-infection-a-possible-implication-for-hbv-glyco-therapy
#16
Shinji Takamatsu, Mayuka Shimomura, Yoshihiro Kamada, Haruka Maeda, Tomoaki Sobajima, Hayato Hikita, Masumi Iijima, Yuta Okamoto, Ryo Misaki, Kazuhito Fujiyama, Shushi Nagamori, Yoshikatsu Kanai, Tetsuo Takehara, Keiji Ueda, Shun'ichi Kuroda, Eiji Miyoshi
The functions of cell surface proteins, such as growth factor receptors and virus/bacteria-entry receptors, can be dynamically regulated by oligosaccharide modifications. In the present study, we investigated the involvement of glycosylation in hepatitis B virus (HBV) entry into hepatoma cells. Infection of oligosaccharide-remodeling hepatoma cells with a pseudo virus of HBV, bio-nanocapsule (BNC), was evaluated by flow cytometry and confocal microscopy. Among various experiments using several hepatoma cells, marked difference was observed between Huh6 cells and HB611 cells, which were established by HBV gene transfection into hepatoma cells...
June 21, 2016: Glycobiology
https://www.readbyqxmd.com/read/27278060/sodium-taurocholate-cotransporting-polypeptide-inhibition-efficiently-blocks-hepatitis-b-virus-spread-in-mice-with-a-humanized-liver
#17
Tasuku Nakabori, Hayato Hikita, Kazuhiro Murai, Yasutoshi Nozaki, Yugo Kai, Yuki Makino, Yoshinobu Saito, Satoshi Tanaka, Hiroshi Wada, Hidetoshi Eguchi, Takeshi Takahashi, Hiroshi Suemizu, Ryotaro Sakamori, Naoki Hiramatsu, Tomohide Tatsumi, Tetsuo Takehara
Sodium taurocholate cotransporting polypeptide (NTCP) is a recently discovered hepatitis B virus (HBV) receptor. In the present study, we used TK-NOG mice with a humanized liver to examine the impact of endogenous NTCP expression on HBV infection. Upon inoculation with HBV, these mice exhibited clear viremia in 2 weeks, and serum HBV DNA levels gradually increased. The frequency of HBsAg-positive hepatocytes in the liver was 5.1 ± 0.6% at 2 weeks and increased with increasing HBV DNA levels, reaching 92...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27251172/reciprocal-regulation-of-farnesoid-x-receptor-%C3%AE-activity-and-hepatitis-b-virus-replication-in-differentiated-heparg-cells-and-primary-human-hepatocytes
#18
Pauline Radreau, Marine Porcherot, Christophe Ramière, Karim Mouzannar, Vincent Lotteau, Patrice André
Hepatitis B virus (HBV) and bile salt metabolism seem tightly connected. HBV enters hepatocytes by binding to sodium taurocholate cotransporting polypeptide (NTCP), the genome of which contains 2 active farnesoid X receptor (FXR) α response elements that participate in HBV transcriptional activity. We investigated in differentiated HepaRG cells and in primary human hepatocytes (PHHs) effects of FXR activation on HBV replication and of infection on the FXR pathway. In HepaRG cells, FXR agonists (6-ethyl chenodeoxycholic acid and GW4064), but no antagonist, and an FXR-unrelated bile salt inhibited viral mRNA, DNA, and protein production (IC50, 0...
September 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27186284/the-combination-of-tacrolimus-and-entecavir-improves-the-remission-of-hbv-associated-glomerulonephritis-without-enhancing-viral-replication
#19
Lifen Wang, Zhiming Ye, Huaban Liang, Bin Zhang, Lixia Xu, Zhonglin Feng, Shuangxin Liu, Wei Shi
BACKGROUND: Tacrolimus inhibits hepatitis B virus entry into hepatocytes through targeting the HBV receptor, sodium taurocholate cotransporting polypeptide. This study was performed to evaluate the efficacy and safety of Tacrolimus combined with entecavir antiviral therapy for HBV-associated glomerulonephritis patients with biopsy-proven membranous nephropathy. METHOD: A cohort of 42 patients was enrolled in this retrospective study. Twenty-three patients received Tacrolimus (0...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27170759/bile-acids-act-as-soluble-host-restriction-factors-limiting-cytomegalovirus-replication-in-hepatocytes
#20
Anna-Kathrin Schupp, Mirko Trilling, Stephanie Rattay, Vu Thuy Khanh Le-Trilling, Katrin Haselow, Jan Stindt, Albert Zimmermann, Dieter Häussinger, Hartmut Hengel, Dirk Graf
UNLABELLED: The liver constitutes a prime site of cytomegalovirus (CMV) replication and latency. Hepatocytes produce, secrete, and recycle a chemically diverse set of bile acids, with the result that interactions between bile acids and cytomegalovirus inevitably occur. Here we determined the impact of naturally occurring bile acids on mouse CMV (MCMV) replication. In primary mouse hepatocytes, physiological concentrations of taurochenodeoxycholic acid (TCDC), glycochenodeoxycholic acid, and to a lesser extent taurocholic acid significantly reduced MCMV-induced gene expression and diminished the generation of virus progeny, while several other bile acids did not exert antiviral effects...
August 1, 2016: Journal of Virology
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