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Na + /taurocholate cotransporting polypeptide

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https://www.readbyqxmd.com/read/28280334/mechanism-of-hepatic-targeting-via-oral-administration-of-dspe-peg-cholic-acid-modified-nanoliposomes
#1
Ying Li, Chunyan Zhu
In oral administration, gastrointestinal physiological environment, gastrointestinal epithelial cell membranes, and blood circulation are typical biological barriers to hepatic delivery of ligand-modified nanoparticle drug delivery systems. To elucidate the mechanism of oral hepatic targeting of cholic acid receptor-mediated nanoliposomes (LPs) (distearoyl phosphatidylethanolamine-polyethylene glycol-cholic acid-modified LPs, CA-LPs), evaluations were performed on colon cancer Caco-2 cell monolayers, liver cancer HepG2 cells, and a rat intestinal perfusion model...
2017: International Journal of Nanomedicine
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
#2
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/28214689/paeoniflorin-ameliorates-cholestasis-via-regulating-hepatic-transporters-and-suppressing-inflammation-in-anit-fed-rats
#3
Yanling Zhao, Xuan He, Xiao Ma, Jianxia Wen, Pengyan Li, Jiabo Wang, Ruisheng Li, Yun Zhu, Shizhang Wei, Haotian Li, Xuelin Zhou, Kun Li, Honghong Liu, Xiaohe Xiao
Paeoniflorin has shown the obvious effect on cholestasis according to our previous research. However, its mechanism has not been absolutely explored yet. This study aims at evaluating the potential effect of paeoniflorin on alpha-naphthylisothiocyanate (ANIT) -induced cholestasis by inhibiting nuclear factor kappa-B (NF-κB) and simultaneously regulating hepatocyte transporters. Cholestasis was induced by administration of ANIT. The effect of paeoniflorin on serum indices such as total bilirubin (TBIL), direct bilirubin (DBIL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyltranspeptidase (γ-GT), total bile acid (TBA) and histopathology of liver were determined...
February 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28202577/nimesulide-and-4-hydroxynimesulide-as-bile-acid-transporters-inhibitors-are-contributory-factors-for-drug-induced-cholestasis
#4
Lei Zhou, Xiaoyan Pang, Jingfang Jiang, Dafang Zhong, Xiaoyan Chen
Nimesulide (NIM) is a classic nonsteroidal anti-inflammatory drug. However, some patients treated with NIM experienced cholestatic liver injury. For this reason, we investigated the potential mechanism underlying NIM-induced cholestasis by using in vivo and in vitro models. Oral administration of 100 mg/kg/day NIM to Wistar rats for 5 days increased the levels of plasma total bile acids, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase by 1.49-, 1.31-, 1.60-, and 1.29-fold, respectively...
May 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
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
#5
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
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
#6
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/28051334/glutamine-attenuates-obstructive-cholestasis-in-rats-via-farnesoid-x-receptor-mediated-regulation-of-bsep-and-mrp2
#7
Bingli Liu, Yiming Li, Hong Ji, Hongwei Lu, Hua Li, Yakun Shi
To investigate the protective effect of glutamine (Gln) against obstructive cholestasis in association with farnesoid X receptor (FXR) activation, an obstructive cholestasis model was established in male Sprague-Dawley rats by bile duct ligation (BDL). Serum biomarkers and hematoxylin plus eosin staining were used to identify the degree of hepatic injury in the rats with obstructive cholestasis after Gln treatment. Immunohistochemistry, real-time PCR, Western blot, cultured primary rat hepatocytes with FXR knockdown, and dual-luciferase reporter assay were performed to elucidate the mechanisms underlying Gln hepatoprotection...
October 5, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28013215/organic-anion-transporting-polypeptides-contribute-to-the-disposition-of-perfluoroalkyl-acids-in-humans-and-rats
#8
Wen Zhao, Jeremiah D Zitzow, Yi Weaver, David J Ehresman, Shu-Ching Chang, John L Butenhoff, Bruno Hagenbuch
Perfluoroalkyl sulfonates (PFSAs) such as perfluorohexane sulfonate (PFHxS) and perfluorooctane sulfonate (PFOS) have very long serum elimination half-lives in humans, and preferentially distribute to serum and liver. The enterohepatic circulation of PFHxS and PFOS likely contributes to their extended elimination half-lives. We previously demonstrated that perfluorobutane sulfonate (PFBS), PFHxS, and PFOS are transported into hepatocytes both in a sodium-dependent and a sodium-independent manner. We identified Na+/taurocholate cotransporting polypeptide (NTCP) as the responsible sodium-dependent transporter...
March 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/27676153/inhibition-of-hepatobiliary-transport-activity-by-the-antibacterial-agent-fusidic-acid-insights-into-factors-contributing-to-conjugated-hyperbilirubinemia-cholestasis
#9
Kimberly Lapham, Jonathan Novak, Lisa D Marroquin, Rachel Swiss, Shuzhen Qin, Christopher J Strock, Renato Scialis, Michael D Aleo, Thomas Schroeter, Heather Eng, A David Rodrigues, Amit S Kalgutkar
Conjugated hyperbilirubinemia accompanied by cholestasis is a frequent side effect during chronic treatment with the antimicrobial agent fusidic acid. Previous studies from our laboratory, addressing mechanisms of musculoskeletal toxicity arising from coadministration of fusidic acid with statins, demonstrated the ability of fusidic acid to potently inhibit human organic anion transporting polypeptides OATP1B1 (IC50 = 1.6 μM) and OATP1B3 (IC50 = 2.5 μM), which are responsible for the uptake-limited clearance of statins as well as bilirubin glucuronide conjugates...
October 4, 2016: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/27451430/regulation-of-plasma-membrane-localization-of-the-na-taurocholate-cotransporting-polypeptide-ntcp-by-hyperosmolarity-and-tauroursodeoxycholate
#10
Annika Sommerfeld, Patrick G K Mayer, Miriam Cantore, Dieter Häussinger
No abstract text is available yet for this article.
July 22, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27406326/bile-acids-induce-necrosis-in-pancreatic-stellate-cells-dependent-on-calcium-entry-and-sodium-driven-bile-uptake
#11
Pawel E Ferdek, Monika A Jakubowska, Julia V Gerasimenko, Oleg V Gerasimenko, Ole H Petersen
KEY POINTS: Acute biliary pancreatitis is a sudden and severe condition initiated by bile reflux into the pancreas. Bile acids are known to induce Ca(2+) signals and necrosis in isolated pancreatic acinar cells but the effects of bile acids on stellate cells are unexplored. Here we show that cholate and taurocholate elicit more dramatic Ca(2+) signals and necrosis in stellate cells compared to the adjacent acinar cells in pancreatic lobules; whereas taurolithocholic acid 3-sulfate primarily affects acinar cells...
November 1, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27160211/optimized-hepatocyte-like-cells-with-functional-drug-transporters-directly-reprogrammed-from-mouse-fibroblasts-and-their-potential-in-drug-disposition-and-toxicology
#12
Zhi-Tao Wu, Dan Yao, Shu-Yi Ji, Xuan Ni, Yi-Meng Gao, Li-Jian Hui, Guo-Yu Pan
BACKGROUND/AIMS: To develop a suitable hepatocyte-like cell model that could be a substitute for primary hepatocytes with essential transporter expression and functions. Induced hepatocyte-like (iHep) cells directly reprogrammed from mice fibroblast cells were fully characterized. METHODS: Naïve iHep cells were transfected with nuclear hepatocyte factor 4 alpha (Hnf4α) and treated with selected small molecules. Sandwich cultured configuration was applied. The mRNA and protein expression of transporters were determined by Real Time PCR and confocal...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27112167/role-of-multidrug-resistance-protein-3-in-antifungal-induced-cholestasis
#13
Zainab M Mahdi, Uta Synal-Hermanns, Aylin Yoker, Kaspar P Locher, Bruno Stieger
Drug-induced liver injury is an important clinical entity resulting in a considerable number of hospitalizations. While drug-induced cholestasis due to the inhibition of the bile salt export pump (BSEP) is well investigated, only limited information on the interaction of drugs with multidrug resistance protein 3 (MDR3) exists and its role in the pathogenesis of drug-induced cholestasis is poorly understood. Therefore, we aimed to study the interaction of drugs with MDR3 and the effect of drugs on canalicular lipid secretion in a newly established polarized cell line system that serves as a model of canalicular lipid secretion...
July 2016: Molecular Pharmacology
https://www.readbyqxmd.com/read/26699621/stable-human-hepatoma-cell-lines-for-efficient-regulated-expression-of-nucleoside-nucleotide-analog-resistant-and-vaccine-escape-hepatitis-b-virus-variants-and-woolly-monkey-hepatitis-b-virus
#14
Xin Cheng, Weiwei Guan, Shuo Sun, Baosheng Li, Haijun Li, Fubiao Kang, Jiwen Kang, Dongliang Yang, Michael Nassal, Dianxing Sun
Hepatitis B virus (HBV) causes acute and chronic hepatitis B (CHB). Due to its error-prone replication via reverse transcription, HBV can rapidly evolve variants that escape vaccination and/or become resistant to CHB treatment with nucleoside/nucleotide analogs (NAs). This is particularly problematic for the first generation NAs lamivudine and adefovir. Though now superseded by more potent NAs, both are still widely used. Furthermore, resistance against the older NAs can contribute to cross-resistance against more advanced NAs...
2015: PloS One
https://www.readbyqxmd.com/read/26684275/increased-bile-acid-synthesis-and-impaired-bile-acid-transport-in-human-obesity
#15
Rebecca A Haeusler, Stefania Camastra, Monica Nannipieri, Brenno Astiarraga, Jose Castro-Perez, Dan Xie, Liangsu Wang, Manu Chakravarthy, Ele Ferrannini
CONTEXT: Alterations in bile acid (BA) synthesis and transport have the potential to affect multiple metabolic pathways in the pathophysiology of obesity. OBJECTIVE: The objective of the study was to investigate the effects of obesity on serum fluctuations of BAs and markers of BA synthesis. DESIGN: We measured BA fluctuations in 11 nonobese and 32 obese subjects and BA transporter expression in liver specimens from 42 individuals and specimens of duodenum, jejunum, ileum, colon, and pancreas from nine individuals...
May 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/26679606/hepatic-maturation-of-human-ips-cell-derived-hepatocyte-like-cells-by-atf5-c-ebp%C3%AE-and-prox1-transduction
#16
Daiki Nakamori, Kazuo Takayama, Yasuhito Nagamoto, Seiji Mitani, Fuminori Sakurai, Masashi Tachibana, Hiroyuki Mizuguchi
Hepatocyte-like cells differentiated from human iPS cells (human iPS-HLCs) are expected to be utilized in drug development and research. However, recent hepatic characterization of human iPS-HLCs showed that these cells resemble fetal hepatocytes rather than adult hepatocytes. Therefore, in this study, we aimed to develop a method to enhance the hepatic function of human iPS-HLCs. Because the gene expression levels of the hepatic transcription factors (activating transcription factor 5 (ATF5), CCAAT/enhancer-binding protein alpha (c/EBPα), and prospero homeobox protein 1 (PROX1)) in adult liver were significantly higher than those in human iPS-HLCs and fetal liver, we expected that the hepatic functions of human iPS-HLCs could be enhanced by adenovirus (Ad) vector-mediated ATF5, c/EBPα, and PROX1 transduction...
January 15, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/26650232/the-na-taurocholate-cotransporting-polypeptide-traffics-with-the-epidermal-growth-factor-receptor
#17
Xintao Wang, Pijun Wang, Wenjun Wang, John W Murray, Allan W Wolkoff
Na(+)-taurocholate cotransporting polypeptide (ntcp) mediates bile acid transport, also serving as the hepatitis B virus receptor. It traffics in vesicles along microtubules, requiring activity of protein kinase C (PKC)ζ for motility. We have now found that the epidermal growth factor receptor (EGFR) is the target of PKCζ activity and that EGFR and ntcp colocalize in vesicles. ntcp-containing vesicles that are not associated with EGFR have reduced microtubule-based motility, consistent with intracellular accumulation and reduced surface expression of ntcp in cells following EGFR knockdown...
March 2016: Traffic
https://www.readbyqxmd.com/read/26453540/high-dietary-cholesterol-and-ovariectomy-in-rats-repress-gene-expression-of-key-markers-of-vldl-and-bile-acid-metabolism-in-liver
#18
Zahra Farahnak, Isabelle Côté, Emilienne T Ngo Sock, Jean-Marc Lavoie
BACKGROUND: The purpose of the study was to evaluate the effects of high dietary cholesterol in ovariectomized (Ovx) rats on several key markers of hepatic cholesterol and bile acid metabolism. METHOD: Ovx and sham operated (Sham) rats were given either a standard diet (SD), a SD diet supplemented with 0.25% cholesterol (SD + Chol), or a high fat diet supplemented with 0.25% cholesterol (HF + Chol) for 5 weeks. RESULTS: Ovx was associated with higher (P < 0...
2015: Lipids in Health and Disease
https://www.readbyqxmd.com/read/26378168/a-novel-tricyclic-polyketide-vanitaracin-a-specifically-inhibits-the-entry-of-hepatitis-b-and-d-viruses-by-targeting-sodium-taurocholate-cotransporting-polypeptide
#19
Manabu Kaneko, Koichi Watashi, Shinji Kamisuki, Hiroki Matsunaga, Masashi Iwamoto, Fumihiro Kawai, Hirofumi Ohashi, Senko Tsukuda, Satomi Shimura, Ryosuke Suzuki, Hideki Aizaki, Masaya Sugiyama, Sam-Yong Park, Takayoshi Ito, Naoko Ohtani, Fumio Sugawara, Yasuhito Tanaka, Masashi Mizokami, Camille Sureau, Takaji Wakita
UNLABELLED: Anti-hepatitis B virus (HBV) drugs are currently limited to nucleos(t)ide analogs (NAs) and interferons. A challenge of drug development is the identification of small molecules that suppress HBV infection from new chemical sources. Here, from a fungus-derived secondary metabolite library, we identify a structurally novel tricyclic polyketide, named vanitaracin A, which specifically inhibits HBV infection. Vanitaracin A inhibited the viral entry process with a submicromolar 50% inhibitory concentration (IC50) (IC50 = 0...
December 2015: Journal of Virology
https://www.readbyqxmd.com/read/26310603/novel-reporter-system-to-monitor-early-stages-of-the-hepatitis-b-virus-life-cycle
#20
Hironori Nishitsuji, Saneyuki Ujino, Yuko Shimizu, Keisuke Harada, Jing Zhang, Masaya Sugiyama, Masashi Mizokami, Kunitada Shimotohno
A recombinant hepatitis B virus (HBV) expressing NanoLuc (NL) (HBV/NL) was produced by cotransfecting a plasmid containing a 1.2-fold HBV genome carrying the NL gene with a plasmid bearing a packaging-defective 1.2-fold HBV genome into a human hepatoma cell line, HepG2. We found that NL activity in HBV/NL-infected primary hepatocytes or sodium taurocholate cotransporting polypeptide-transduced human hepatocyte-derived cell lines increased linearly for several days after infection and was concordant with HBV RNA levels in the cells...
November 2015: Cancer Science
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