The Role of the Sodium-taurocholate Co-transporting Polypeptide (NTCP) and Bile Salt Export Pump (BSEP) in Related Liver Disease

Author(s): Xiaoyang Lu, Lin Liu, Wenya Shan, Limin Kong, Na Chen, Yan Lou*, Su Zeng.

Journal Name: Current Drug Metabolism

Volume 20 , Issue 5 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: Sodium Taurocholate Co-transporting Polypeptide (NTCP) and Bile Salt Export Pump (BSEP) play significant roles as membrane transporters because of their presence in the enterohepatic circulation of bile salts. They have emerged as promising drug targets in related liver disease.

Methods: We reviewed the literature published over the last 20 years with a focus on NTCP and BSEP.

Results: This review summarizes the current perception about structure, function, genetic variation, and regulation of NTCP and BSEP, highlights the effects of their defects in some hepatic disorders, and discusses the application prospect of new transcriptional activators in liver diseases.

Conclusion: NTCP and BSEP are important proteins for transportation and homeostasis maintenance of bile acids. Further research is needed to develop new models for determining the structure-function relationship of bile acid transporters and screening for substrates and inhibitors, as well as to gain more information about the regulatory genetic mechanisms involved in the processes of liver injury.

Keywords: NTCP and BSEP, expression and function, genetic variants, liver disease, transcriptional regulation, substrates and inhibitors.

[1]
Trauner, M.; Boyer, J.L. Bile salt transporters: Molecular characterization, function, and regulation. Physiol. Rev., 2003, 83, 633-671.
[2]
Stieger, B.; Geier, A. Genetic variations of bile salt transporters as predisposing factors for drug-induced cholestasis, intrahepatic cholestasis of pregnancy and therapeutic response of viral hepatitis. Expert Opin. Drug Metab. Toxicol., 2011, 7, 411-425.
[3]
Stieger, B. The role of the Sodium-taurocholate Cotransporting Polypeptide (NTCP) and of the Bile Salt Export Pump (BSEP) in physiology and pathophysiology of bile formation. Handb. Exp. Pharmacol., 2011, 201, 205-259.
[4]
Ferrebee, C.B.; Dawson, P.A. Metabolic effects of intestinal absorption and enterohepatic cycling of bile acids. Acta Pharm. Sin. B, 2015, 5, 129-134.
[5]
Sokol, R.J.; Devereaux, M.; Dahl, R.; Gumpricht, E. “Let there be bile”-understanding hepatic injury in cholestasis. J. Pediatr. Gastroenterol. Nutr., 2006, 43(Suppl. 1), S4-S9.
[6]
Kosters, A.; Karpen, S.J. Bile acid transporters in health and disease. Xenobiotica, 2008, 38, 1043-1071.
[7]
Kubitz, R.; Droge, C.; Kluge, S.; Stindt, J.; Haussinger, D. Genetic variations of bile salt transporters. Drug Discov. Today. Technol., 2014, 12, e55-e67.
[8]
Alrefai, W.A.; Gill, R.K. Bile acid transporters: Structure, function, regulation and pathophysiological implications. Pharm. Res., 2007, 24, 1803-1823.
[9]
Baghdasaryan, A.; Chiba, P.; Trauner, M. Clinical application of transcriptional activators of bile salt transporters. Mol. Aspects Med., 2014, 37, 57-76.
[10]
Claro, D.S.T.; Polli, J.E.; Swaan, P.W. The solute carrier family 10 (SLC10): Beyond bile acid transport. Mol. Aspects Med., 2013, 34, 252-269.
[11]
Anwer, M.S.; Stieger, B. Sodium-dependent bile salt transporters of the SLC10A transporter family: More than solute transporters. Pflugers Arch., 2014, 466, 77-89.
[12]
Kullak-Ublick, G.A.; Glasa, J.; Boker, C.; Oswald, M.; Grutzner, U.; Hagenbuch, B.; Stieger, B.; Meier, P.J.; Beuers, U.; Kramer, W.; Wess, G.; Paumgartner, G. Chlorambucil-taurocholate is transported by bile acid carriers expressed in human hepatocellular carcinomas. Gastroenterology, 1997, 113, 1295-1305.
[13]
Kim, J.Y.; Kim, K.H.; Lee, J.A.; Namkung, W.; Sun, A.Q.; Ananthanarayanan, M.; Suchy, F.J.; Shin, D.M.; Muallem, S.; Lee, M.G. Transporter-mediated bile acid uptake causes Ca2+-dependent cell death in rat pancreatic acinar cells. Gastroenterology, 2002, 122, 1941-1953.
[14]
Zollner, G.; Fickert, P.; Silbert, D.; Fuchsbichler, A.; Marschall, H.U.; Zatloukal, K.; Denk, H.; Trauner, M. Adaptive changes in hepatobiliary transporter expression in primary biliary cirrhosis. J. Hepatol., 2003, 38, 717-727.
[15]
Kang, J.; Wang, J.; Cheng, J.; Cao, Z.; Chen, R.; Li, H.; Liu, S.; Chen, X.; Sui, J.; Lu, F. Down-regulation of NTCP expression by cyclin D1 in hepatitis B virus-related hepatocellular carcinoma has clinical significance. Oncotarget, 2017, 8, 56041-56050.
[16]
Verrier, E.R.; Colpitts, C.C.; Bach, C.; Heydmann, L.; Zona, L.; Xiao, F.; Thumann, C.; Crouchet, E.; Gaudin, R.; Sureau, C.; Cosset, F.L.; McKeating, J.A.; Pessaux, P.; Hoshida, Y.; Schuster, C.; Zeisel, M.B.; Baumert, T.F. Solute carrier NTCP regulates innate antiviral immune responses targeting hepatitis C virus infection of hepatocytes. Cell Reports, 2016, 17, 1357-1368.
[17]
Ho, R.H.; Leake, B.F.; Roberts, R.L.; Lee, W.; Kim, R.B. Ethnicity-dependent polymorphism in Na+-taurocholate cotransporting polypeptide (SLC10A1) reveals a domain critical for bile acid substrate recognition. J. Biol. Chem., 2004, 279, 7213-7222.
[18]
Su, Z.; Li, Y.; Liao, Y.; Cai, B.; Chen, J.; Zhang, J.; Li, L.; Ying, B.; Tao, C.; Wang, L. Association of the gene polymorphisms in sodium taurocholate cotransporting polypeptide with the outcomes of hepatitis B infection in Chinese Han population. Infect. Genet. Evol., 2014, 27, 77-82.
[19]
Peng, L.; Zhao, Q.; Li, Q.; Li, M.; Li, C.; Xu, T.; Jing, X.; Zhu, X.; Wang, Y.; Li, F.; Liu, R.; Zhong, C.; Pan, Q.; Zeng, B.; Liao, Q.; Hu, B.; Hu, Z.X.; Huang, Y.S.; Sham, P.; Liu, J.; Xu, S.; Wang, J.; Gao, Z.L.; Wang, Y. The p.Ser267Phe variant in SLC10A1 is associated with resistance to chronic hepatitis B. Hepatology, 2015, 61, 1251-1260.
[20]
Vaz, F.M.; Paulusma, C.C.; Huidekoper, H.; De Ru, M.; Lim, C.; Koster, J.; Ho-Mok, K.; Bootsma, A.H.; Groen, A.K.; Schaap, F.G.; Oude, E.R.P.; Waterham, H.R.; Wanders, R.J. Sodium taurocholate cotransporting polypeptide (SLC10A1) deficiency: Conjugated hypercholanemia without a clear clinical phenotype. Hepatology, 2015, 61, 260-267.
[21]
Wei, P. Genetic polymorphisms in Na+-taurocholate Co-transporting Polypeptide (NTCP) and ileal Apical Sodium-dependent Bile Acid Transporter (ASBT) and ethnic comparisons of functional variants of NTCP among Asian populations. Xenobiotica, 2011, 6, 501-510.
[22]
Yu, Y.; Li, S.; Liang, W. Bona fide receptor for hepatitis B and D viral infections: Mechanism, research models and molecular drug targets. Microbes Infect., 2018, 7, 134.
[23]
Ho, R.H.; Tirona, R.G.; Leake, B.F.; Glaeser, H.; Lee, W.; Lemke, C.J.; Wang, Y.; Kim, R.B. Drug and bile acid transporters in rosuvastatin hepatic uptake: Function, expression, and pharmacogenetics. Gastroenterology, 2006, 130, 1793-1806.
[24]
Yan, H.; Zhong, G.; Xu, G.; He, W.; Jing, Z.; Gao, Z.; Huang, Y.; Qi, Y.; Peng, B.; Wang, H.; Fu, L.; Song, M.; Chen, P.; Gao, W.; Ren, B.; Sun, Y.; Cai, T.; Feng, X.; Sui, J.; Li, W. Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. eLife, 2012, 1, e00049.
[25]
Ni, Y.; Lempp, F.A.; Mehrle, S.; Nkongolo, S.; Kaufman, C.; Falth, M.; Stindt, J.; Koniger, C.; Nassal, M.; Kubitz, R.; Sultmann, H.; Urban, S. Hepatitis B and D viruses exploit sodium taurocholate co-transporting polypeptide for species-specific entry into hepatocytes. Gastroenterology, 2014, 146, 1070-1083.
[26]
Yan, H.; Peng, B.; Liu, Y.; Xu, G.; He, W.; Ren, B.; Jing, Z.; Sui, J.; Li, W. Viral entry of hepatitis B and D viruses and bile salts transportation share common molecular determinants on sodium taurocholate cotransporting polypeptide. J. Virol., 2014, 88, 3273-3284.
[27]
Jung, D.; Kullak-Ublick, G.A. Hepatocyte nuclear factor 1 alpha: A key mediator of the effect of bile acids on gene expression. Hepatology, 2003, 37, 622-631.
[28]
Jang, E.S.; Yoon, J.H.; Lee, S.H.; Lee, S.M.; Lee, J.H.; Yu, S.J.; Kim, Y.J.; Lee, H.S.; Kim, C.Y. Sodium taurocholate cotransporting polypeptide mediates dual actions of deoxycholic acid in human hepatocellular carcinoma cells: enhanced apoptosis versus growth stimulation. J. Cancer Res. Clin. Oncol., 2014, 140, 133-144.
[29]
Simon, F.R.; Fortune, J.; Iwahashi, M.; Qadri, I.; Sutherland, E. Multihormonal regulation of hepatic sinusoidal Ntcp gene expression. Am. J. Physiol. Gastrointest. Liver Physiol., 2004, 287, G782-G794.
[30]
Mita, S.; Suzuki, H.; Akita, H.; Hayashi, H.; Onuki, R.; Hofmann, A.F.; Sugiyama, Y. Vectorial transport of unconjugated and conjugated bile salts by monolayers of LLC-PK1 cells doubly transfected with human NTCP and BSEP or with rat NTCP and BSEP. Am. J. Physiol. Gastrointest. Liver Physiol., 2006, 290, G550-G556.
[31]
Briz, O.; Serrano, M.A.; Rebollo, N.; Hagenbuch, B.; Meier, P.J.; Koepsell, H.; Marin, J.J. Carriers involved in targeting the cytostatic bile acid-cisplatin derivatives cis-diammine-chloro-cholylglycinate-platinum(II) and cis-diammine-bisursodeoxycholate-platinum(II) toward liver cells. Mol. Pharmacol., 2002, 61, 853-860.
[32]
Grosser, G.; Doring, B.; Ugele, B.; Geyer, J.; Kulling, S.E.; Soukup, S.T. Transport of the soy isoflavone daidzein and its conjugative metabolites by the carriers SOAT, NTCP, OAT4, and OATP2B1. Arch. Toxicol., 2015, 89, 2253-2263.
[33]
Fu, L.L.; Liu, J.; Chen, Y.; Wang, F.T.; Wen, X.; Liu, H.Q.; Wang, M.Y.; Ouyang, L.; Huang, J.; Bao, J.K.; Wei, Y.Q. In silico analysis and experimental validation of azelastine hydrochloride (N4) targeting sodium taurocholate co-transporting polypeptide (NTCP) in HBV therapy. Cell Prolif., 2014, 47, 326-335.
[34]
Mita, S.; Suzuki, H.; Akita, H.; Hayashi, H.; Onuki, R.; Hofmann, A.F.; Sugiyama, Y. Inhibition of bile acid transport across Na+/taurocholate cotransporting polypeptide (SLC10A1) and bile salt export pump (ABCB 11)-coexpressing LLC-PK1 cells by cholestasis-inducing drugs. Drug Metab. Dispos., 2006, 34, 1575-1581.
[35]
Kim, R.B.; Leake, B.; Cvetkovic, M.; Roden, M.M.; Nadeau, J.; Walubo, A.; Wilkinson, G.R. Modulation by drugs of human hepatic sodium-dependent bile acid transporter (sodium taurocholate cotransporting polypeptide) activity. J. Pharmacol. Exp. Ther., 1999, 291, 1204-1209.
[36]
McRae, M.P.; Lowe, C.M.; Tian, X.; Bourdet, D.L.; Ho, R.H.; Leake, B.F.; Kim, R.B.; Brouwer, K.L.; Kashuba, A.D. Ritonavir, saquinavir, and efavirenz, but not nevirapine, inhibit bile acid transport in human and rat hepatocytes. J. Pharmacol. Exp. Ther., 2006, 318, 1068-1075.
[37]
Leslie, E.M.; Watkins, P.B.; Kim, R.B.; Brouwer, K.L. Differential inhibition of rat and human Na+-dependent taurocholate cotransporting polypeptide (NTCP/SLC10A1) by bosentan: A mechanism for species differences in hepatotoxicity. J. Pharmacol. Exp. Ther., 2007, 321, 1170-1178.
[38]
Lepist, E.I.; Gillies, H.; Smith, W.; Hao, J.; Hubert, C.; St, C.R.L., III; Brouwer, K.R.; Ray, A.S. Evaluation of the endothelin receptor antagonists ambrisentan, bosentan, macitentan, and sitaxsentan as hepatobiliary transporter inhibitors and substrates in sandwich-cultured human hepatocytes. PLoS One, 2014, 9, e87548.
[39]
Hagenbuch, B.; Meier, P.J. Molecular cloning, chromosomal localization, and functional characterization of a human liver Na+/bile acid cotransporter. J. Clin. Invest., 1994, 93, 1326-1331.
[40]
Greupink, R.; Nabuurs, S.B.; Zarzycka, B.; Verweij, V.; Monshouwer, M.; Huisman, M.T.; Russel, F.G. In silico identification of potential cholestasis-inducing agents via modeling of Na(+)-dependent taurocholate cotransporting polypeptide substrate specificity. Toxicol. Sci., 2012, 129, 35-48.
[41]
Seeger, C.; Sohn, J.A. Targeting hepatitis b virus with CRISPR/Cas9. Mol. Ther. Nucleic Acids, 2014, 3, e216.
[42]
Iwamoto, M.; Watashi, K.; Tsukuda, S.; Aly, H.H.; Fukasawa, M.; Fujimoto, A.; Suzuki, R.; Aizaki, H.; Ito, T.; Koiwai, O.; Kusuhara, H.; Wakita, T. Evaluation and identification of hepatitis B virus entry inhibitors using HepG2 cells overexpressing a membrane transporter NTCP. Biochem. Biophys. Res. Commun., 2014, 443, 808-813.
[43]
Dong, Z.; Ekins, S.; Polli, J.E. A substrate pharmacophore for the human sodium taurocholate co-transporting polypeptide. Int. J. Pharm., 2015, 478, 88-95.
[44]
Shen, Z.W.; Luo, M.Y.; Hu, H.H.; Zhou, H.; Jiang, H.D.; Yu, L.S.; Zeng, S. Screening and verifying potential NTCP inhibitors from herbal medicinal ingredients using the LLC-PK1 cell model stably expressing human NTCP. Chin. J. Nat. Med., 2016, 14, 549-560.
[45]
Craddock, A.L.; Love, M.W.; Daniel, R.W.; Kirby, L.C.; Walters, H.C.; Wong, M.H.; Dawson, P.A. Expression and transport properties of the human ileal and renal sodium-dependent bile acid transporter. Am. J. Physiol., 1998, 274, G157-G169.
[46]
Maeda, K.; Kambara, M.; Tian, Y.; Hofmann, A.F.; Sugiyama, Y. Uptake of ursodeoxycholate and its conjugates by human hepatocytes: Role of Na(+)-taurocholate Cotransporting Polypeptide (NTCP), Organic Anion Transporting Polypeptide (OATP) 1B1 (OATP-C), and oatp1B3 (OATP8). Mol. Pharm., 2006, 3, 70-77.
[47]
Yabuuchi, H.; Tanaka, K.; Maeda, M.; Takemura, M.; Oka, M.; Ohashi, R.; Tamai, I. Cloning of the dog bile salt export pump (BSEP; ABCB11) and functional comparison with the human and rat proteins. Biopharm. Drug Dispos., 2008, 29, 441-448.
[48]
Meier, P.J.; Eckhardt, U.; Schroeder, A.; Hagenbuch, B.; Stieger, B. Substrate specificity of sinusoidal bile acid and organic anion uptake systems in rat and human liver. Hepatology, 1997, 26, 1667-1677.
[49]
Greupink, R.; Dillen, L.; Monshouwer, M.; Huisman, M.T.; Russel, F.G. Interaction of fluvastatin with the liver-specific Na+ -dependent Taurocholate Cotransporting Polypeptide (NTCP). Eur. J. Pharm. Sci., 2011, 44, 487-496.
[50]
Choi, M.K.; Shin, H.J.; Choi, Y.L.; Deng, J.W.; Shin, J.G.; Song, I.S. Differential effect of genetic variants of Na(+)-taurocholate Co-Transporting Polypeptide (NTCP) and Organic anion-transporting Polypeptide 1B1 (OATP1B1) on the uptake of HMG-CoA reductase inhibitors. Xenobiotica, 2011, 41, 24-34.
[51]
Visser, W.E.; Wong, W.S.; van Mullem, A.A.; Friesema, E.C.; Geyer, J.; Visser, T.J. Study of the transport of thyroid hormone by transporters of the SLC10 family. Mol. Cell. Endocrinol., 2010, 315, 138-145.
[52]
Gozalpour, E.; Greupink, R.; Wortelboer, H.M.; Bilos, A.; Schreurs, M.; Russel, F.G.; Koenderink, J.B. Interaction of digitalis-like compounds with liver uptake transporters NTCP, OATP1B1, and OATP1B3. Mol. Pharm., 2014, 11, 1844-1855.
[53]
Telbisz, A.; Homolya, L. Recent advances in the exploration of the bile salt export pump (BSEP/ABCB11) function. Expert Opin. Ther. Targets, 2016, 20, 501-514.
[54]
Le, V.M.; Jouan, E.; Noel, G.; Stieger, B.; Fardel, O. Polarized location of SLC and ABC drug transporters in monolayer-cultured human hepatocytes. Toxicol. In Vitro, 2015, 29, 938-946.
[55]
Kubitz, R.; Sutfels, G.; Kuhlkamp, T.; Kolling, R.; Haussinger, D. Trafficking of the bile salt export pump from the Golgi to the canalicular membrane is regulated by the p38 MAP kinase. Gastroenterology, 2004, 126, 541-553.
[56]
Gyimesi, G.; Borsodi, D.; Saranko, H.; Tordai, H.; Sarkadi, B.; Hegedus, T. ABCMdb: A database for the comparative analysis of protein mutations in ABC transporters, and a potential framework for a general application. Hum. Mutat., 2012, 33, 1547-1556.
[57]
Liu, L.; Zhang, L.; Zhang, L.; Yang, F.; Zhu, X.; Lu, Z.; Yang, Y.; Lu, H.; Feng, L.; Wang, Z.; Chen, H.; Yan, S.; Wang, L.; Ju, Z.; Jin, H.; Zhu, X. Hepatic Tmem30a deficiency causes intrahepatic cholestasis by impairing expression and localization of bile salt transporters. Am. J. Pathol., 2017, 187, 2775-2787.
[58]
Lam, P.; Pearson, C.L.; Soroka, C.J.; Xu, S.; Mennone, A.; Boyer, J.L. Levels of plasma membrane expression in progressive and benign mutations of the bile salt export pump (Bsep/Abcb11) correlate with severity of cholestatic diseases. Am. J. Physiol. Cell Physiol., 2007, 293, C1709-C1716.
[59]
Ellinger, P.; Stindt, J.; Droge, C.; Sattler, K.; Stross, C.; Kluge, S.; Herebian, D. SHJ, S.; Burdelski, M.; Schulz-Jurgensen, S.; Ballauff, A.; Schulte, A.E.J.; Mayatepek, E.; Haussinger, D.; Kubitz, R.; Schmitt, L. Partial external biliary diversion in bile salt export pump deficiency: Association between outcome and mutation. World J. Gastroenterol., 2017, 23, 5295-5303.
[60]
Droge, C.; Schaal, H.; Engelmann, G.; Wenning, D.; Haussinger, D.; Kubitz, R. Exon-skipping and mRNA decay in human liver tissue: Molecular consequences of pathogenic bile salt export pump mutations. Sci. Rep., 2016, 6, 24827.
[61]
Glantz, A.; Reilly, S.J.; Benthin, L.; Lammert, F.; Mattsson, L.A.; Marschall, H.U. Intrahepatic cholestasis of pregnancy: Amelioration of pruritus by UDCA is associated with decreased progesterone disulphates in urine. Hepatology, 2008, 47, 544-551.
[62]
Byrne, J.A.; Strautnieks, S.S.; Ihrke, G.; Pagani, F.; Knisely, A.S.; Linton, K.J.; Mieli-Vergani, G.; Thompson, R.J. Missense mutations and single nucleotide polymorphisms in ABCB11 impair bile salt export pump processing and function or disrupt pre-messenger RNA splicing. Hepatology, 2009, 49, 553-567.
[63]
Kenna, J.G.; Taskar, K.S.; Battista, C.; Bourdet, D.L. KLR, B.; Brouwer, K.R.; Dai, D.; Funk, C.; Hafey, M.J.; Lai, Y.; Maher, J.; Pak, Y.A.; Pedersen, J.M.; Polli, J.W.; Rodrigues, A.D.; Watkins, P.B.; Yang, K.; Yucha, R.W. Can bile salt export pump inhibition testing in drug discovery and development reduce liver injury risk? An international transporter consortium perspective. Clin. Pharmacol. Ther., 2018, 104, 916-932.
[64]
Cheng, Y.; Chen, S.; Freeden, C.; Chen, W.; Zhang, Y.; Abraham, P.; Nelson, D.M.; Humphreys, W.G.; Gan, J.; Lai, Y. Bile salt homeostasis in normal and BSEP gene knockout rats with single and repeated doses of troglitazone. J. Pharmacol. Exp. Ther., 2017, 362, 385-394.
[65]
Kubitz, R.; Droge, C.; Stindt, J.; Weissenberger, K.; Haussinger, D. The Bile Salt Export Pump (BSEP) in health and disease. Clin. Res. Hepatol. Gastroenterol., 2012, 36, 536-553.
[66]
Park, J.S.; Ko, J.S.; Seo, J.K.; Moon, J.S.; Park, S.S. Clinical and ABCB11 profiles in Korean infants with progressive familial intrahepatic cholestasis. World J. Gastroenterol., 2016, 22, 4901-4907.
[67]
Gonzales, E.; Taylor, S.A.; Davit-Spraul, A.; Thebaut, A.; Thomassin, N.; Guettier, C.; Whitington, P.F.; Jacquemin, E. MYO5B mutations cause cholestasis with normal serum gamma-glutamyl transferase activity in children without microvillous inclusion disease. Hepatology, 2017, 65, 164-173.
[68]
Strautnieks, S.S.; Byrne, J.A.; Pawlikowska, L.; Cebecauerova, D.; Rayner, A.; Dutton, L.; Meier, Y.; Antoniou, A.; Stieger, B.; Arnell, H.; Ozcay, F.; Al-Hussaini, H.F.; Bassas, A.F.; Verkade, H.J.; Fischler, B.; Nemeth, A.; Kotalova, R.; Shneider, B.L.; Cielecka-Kuszyk, J.; McClean, P.; Whitington, P.F.; Sokal, E.; Jirsa, M.; Wali, S.H.; Jankowska, I.; Pawlowska, J.; Mieli-Vergani, G.; Knisely, A.S.; Bull, L.N.; Thompson, R.J. Severe bile salt export pump deficiency: 82 different ABCB11 mutations in 109 families. Gastroenterology, 2008, 134, 1203-1214.
[69]
Song, X.; Vasilenko, A.; Chen, Y.; Valanejad, L.; Verma, R.; Yan, B.; Deng, R. Transcriptional dynamics of bile salt export pump during pregnancy: Mechanisms and implications in intrahepatic cholestasis of pregnancy. Hepatology, 2014, 60, 1993-2007.
[70]
Jorquera, F.; Monte, M.J.; Guerra, J.; Sanchez-Campos, S.; Merayo, J.A.; Olcoz, J.L.; Gonzalez-Gallego, J.; Marin, J.J. Usefulness of combined measurement of serum bile acids and ferritin as additional prognostic markers to predict failure to reach sustained response to antiviral treatment in chronic hepatitis C. J. Gastroenterol. Hepatol., 2005, 20, 547-554.
[71]
Iwata, R.; Stieger, B.; Mertens, J.C.; Muller, T.; Baur, K.; Frei, P.; Braun, J.; Vergopoulos, A.; Martin, I.V.; Schmitt, J.; Goetze, O.; Bibert, S.; Bochud, P.Y.; Mullhaupt, B.; Berg, T.; Geier, A. The role of bile acid retention and a common polymorphism in the ABCB11 gene as host factors affecting antiviral treatment response in chronic hepatitis C. J. Viral Hepat., 2011, 18, 768-778.
[72]
Mullenbach, R.; Weber, S.N.; Krawczyk, M.; Zimmer, V.; Sarrazin, C.; Lammert, F.; Grunhage, F. A frequent variant in the human bile salt export pump gene ABCB11 is associated with hepatitis C virus infection, but not liver stiffness in a German population. BMC Gastroenterol., 2012, 12, 63.
[73]
Lei, J.H.; Yang, X.; Xiao, X.Q.; Chen, Z.; Peng, F. A preliminary investigation on single nucleotide polymorphism rs2287622 of bile salt export pump gene in patients with chronic hepatitis C virus infection in Hunan, China. BMC Gastroenterol., 2017, 17, 42.
[74]
Billington, S.; Ray, A.S.; Salphati, L.; Xiao, G.; Chu, X.; Humphreys, W.G.; Liao, M.; Lee, C.A.; Mathias, A. CECA, H.; Rowbottom, C.; Evers, R.; Lai, Y.; Kelly, E.J.; Prasad, B.; Unadkat, J.D. Transporter expression in noncancerous and cancerous liver tissue from donors with hepatocellular carcinoma and chronic hepatitis c infection quantified by LC-MS/MS proteomics. Drug Metab. Dispos., 2018, 46, 189-196.
[75]
Ho, R.H.; Leake, B.F.; Kilkenny, D.M.; Meyer, Z.S.H.E.; Glaeser, H.; Kroetz, D.L.; Kim, R.B. Polymorphic variants in the human Bile Salt Export Pump (BSEP; ABCB11): functional characterization and interindividual variability. Pharmacogenet. Genomics, 2010, 20, 45-57.
[76]
Simmermacher, J.; Sinz, M. Evaluation of farnesoid X receptor target gene induction in human hepatocytes: Amino acid conjugation. Drug Metab. Lett., 2017, 11, 138-143.
[77]
Honjo, Y.; Sasaki, S.; Kobayashi, Y.; Misawa, H.; Nakamura, H. 1,25-dihydroxyvitamin D3 and its receptor inhibit the chenodeoxycholic acid-dependent transactivation by farnesoid X receptor. J. Endocrinol., 2006, 188, 635-643.
[78]
Guo, S.; Zhang, S.; Liu, L.; Yang, P.; Dang, X.; Wei, H.; Hu, N.; Shi, L.; Zhang, Y. Pinelliae rhizoma Praeparatum involved in the regulation of bile acids metabolism in hepatic injury. Biol. Pharm. Bull., 2018, 41, 869-876.
[79]
Homolya, L.; Fu, D.; Sengupta, P.; Jarnik, M.; Gillet, J.P.; Vitale-Cross, L.; Gutkind, J.S.; Lippincott-Schwartz, J.; Arias, I.M. LKB1/AMPK and PKA control ABCB11 trafficking and polarization in hepatocytes. PLoS One, 2014, 9, e91921.
[80]
Misra, S.; Ujhazy, P.; Gatmaitan, Z.; Varticovski, L.; Arias, I.M. The role of phosphoinositide 3-kinase in taurocholate-induced trafficking of ATP-dependent canalicular transporters in rat liver. J. Biol. Chem., 1998, 273, 26638-26644.
[81]
Soroka, C.J.; Boyer, J.L. Biosynthesis and trafficking of the bile salt export pump, BSEP: Therapeutic implications of BSEP mutations. Mol. Aspects Med., 2014, 37, 3-14.
[82]
Marrone, J.; Danielli, M.; Gaspari, C.I.; Marinelli, R.A. Adenovirus-mediated human aquaporin-1 expression in hepatocytes improves lipopolysaccharide-induced cholestasis. IUBMB Life, 2017, 69, 978-984.
[83]
Li, J.; Gong, Y.M.; Wu, J.; Wu, W.J.; Cai, W. Anti-tumor necrosis factor-alpha monoclonal antibody alleviates parenteral nutrition-associated liver disease in mice. JPEN J. Parenter. Enteral Nutr., 2012, 36, 219-225.
[84]
Diao, L.; Li, N.; Brayman, T.G.; Hotz, K.J.; Lai, Y. Regulation of MRP2/ABCC2 and BSEP/ABCB11 expression in sandwich cultured human and rat hepatocytes exposed to inflammatory cytokines TNF-alpha, IL-6, and IL-1beta. J. Biol. Chem., 2010, 285, 31185-31192.
[85]
Kaimal, R.; Song, X.; Yan, B.; King, R.; Deng, R. Differential modulation of farnesoid X receptor signaling pathway by the thiazolidinediones. J. Pharmacol. Exp. Ther., 2009, 330, 125-134.
[86]
Hirano, M.; Maeda, K.; Hayashi, H.; Kusuhara, H.; Sugiyama, Y. Bile Salt Export Pump (BSEP/ABCB11) can transport a nonbile acid substrate, pravastatin. J. Pharmacol. Exp. Ther., 2005, 314, 876-882.
[87]
Daniels, J.S.; Lai, Y.; South, S.; Chiang, P.C.; Walker, D.; Feng, B.; Mireles, R.; Whiteley, L.O.; McKenzie, J.W.; Stevens, J.; Mourey, R.; Anderson, D.; Davis, I.J.W. Inhibition of hepatobiliary transporters by a novel kinase inhibitor contributes to hepatotoxicity in beagle dogs. Drug Metab. Lett., 2013, 7, 15-22.
[88]
Wolters, H.; Kuipers, F.; Slooff, M.J.; Vonk, R.J. Adenosine triphosphate-dependent taurocholate transport in human liver plasma membranes. J. Clin. Invest., 1992, 90, 2321-2326.
[89]
Niinuma, K.; Kato, Y.; Suzuki, H.; Tyson, C.A.; Weizer, V.; Dabbs, J.E.; Froehlich, R.; Green, C.E.; Sugiyama, Y. Primary active transport of organic anions on bile canalicular membrane in humans. Am. J. Physiol., 1999, 276, G1153-G1164.
[90]
Noe, J.; Stieger, B.; Meier, P.J. Functional expression of the canalicular bile salt export pump of human liver. Gastroenterology, 2002, 123, 1659-1666.
[91]
Hayashi, H.; Takada, T.; Suzuki, H.; Onuki, R.; Hofmann, A.F.; Sugiyama, Y. Transport by vesicles of glycine- and taurine-conjugated bile salts and taurolithocholate 3-sulfate: a comparison of human BSEP with rat Bsep. Biochim. Biophys. Acta, 2005, 1738, 54-62.
[92]
Kis, E.; Ioja, E.; Nagy, T.; Szente, L.; Heredi-Szabo, K.; Krajcsi, P. Effect of membrane cholesterol on BSEP/Bsep activity: Species specificity studies for substrates and inhibitors. Drug Metab. Dispos., 2009, 37, 1878-1886.
[93]
Yamaguchi, K.; Murai, T.; Yabuuchi, H.; Kurosawa, T. Measurement of the transport activities of bile salt export pump using LC-MS. Anal. Sci., 2009, 25, 1155-1158.
[94]
Horikawa, M.; Kato, Y.; Tyson, C.A.; Sugiyama, Y. Potential cholestatic activity of various therapeutic agents assessed by bile canalicular membrane vesicles isolated from rats and humans. Drug Metab. Pharmacokinet., 2003, 18, 16-22.
[95]
Feng, B.; Xu, J.J.; Bi, Y.A.; Mireles, R.; Davidson, R.; Duignan, D.B.; Campbell, S.; Kostrubsky, V.E.; Dunn, M.C.; Smith, A.R.; Wang, H.F. Role of hepatic transporters in the disposition and hepatotoxicity of a HER2 tyrosine kinase inhibitor CP-724,714. Toxicol. Sci., 2009, 108, 492-500.
[96]
Kostrubsky, V.E.; Strom, S.C.; Hanson, J.; Urda, E.; Rose, K.; Burliegh, J.; Zocharski, P.; Cai, H.; Sinclair, J.F.; Sahi, J. Evaluation of hepatotoxic potential of drugs by inhibition of bile-acid transport in cultured primary human hepatocytes and intact rats. Toxicol. Sci., 2003, 76, 220-228.
[97]
Hirano, H.; Kurata, A.; Onishi, Y.; Sakurai, A.; Saito, H.; Nakagawa, H.; Nagakura, M.; Tarui, S.; Kanamori, Y.; Kitajima, M.; Ishikawa, T. High-speed screening and QSAR analysis of human ATP-binding cassette transporter ABCB11 (bile salt export pump) to predict drug-induced intrahepatic cholestasis. Mol. Pharm., 2006, 3, 252-265.
[98]
Lang, C.; Meier, Y.; Stieger, B.; Beuers, U.; Lang, T.; Kerb, R.; Kullak-Ublick, G.A.; Meier, P.J.; Pauli-Magnus, C. Mutations and polymorphisms in the bile salt export pump and the multidrug resistance protein 3 associated with drug-induced liver injury. Pharmacogenet. Genomics, 2007, 17, 47-60.
[99]
Funk, C. The role of hepatic transporters in drug elimination. Expert Opin. Drug Metab. Toxicol., 2008, 4, 363-379.
[100]
Kostrubsky, S.E.; Strom, S.C.; Kalgutkar, A.S.; Kulkarni, S.; Atherton, J.; Mireles, R.; Feng, B.; Kubik, R.; Hanson, J.; Urda, E.; Mutlib, A.E. Inhibition of hepatobiliary transport as a predictive method for clinical hepatotoxicity of nefazodone. Toxicol. Sci., 2006, 90, 451-459.
[101]
Mano, Y.; Usui, T.; Kamimura, H. Effects of bosentan, an endothelin receptor antagonist, on bile salt export pump and multidrug resistance-associated protein 2. Biopharm. Drug Dispos., 2007, 28, 13-18.
[102]
Dawson, P.A.; Lan, T.; Rao, A. Bile acid transporters. J. Lipid Res., 2009, 50, 2340-2357.
[103]
Aleo, M.D.; Luo, Y.; Swiss, R.; Bonin, P.D.; Potter, D.M.; Will, Y. Human drug-induced liver injury severity is highly associated with dual inhibition of liver mitochondrial function and bile salt export pump. Hepatology, 2014, 60, 1015-1022.
[104]
Zhang, J.; He, K.; Cai, L.; Chen, Y.C.; Yang, Y.; Shi, Q.; Woolf, T.F.; Ge, W.; Guo, L.; Borlak, J.; Tong, W. Inhibition of bile salt transport by drugs associated with liver injury in primary hepatocytes from human, monkey, dog, rat, and mouse. Chem. Biol. Interact., 2016, 255, 45-54.
[105]
Morgan, R.E.; Van Staden, C.J.; Chen, Y.; Kalyanaraman, N.; Kalanzi, J.; Dunn, R.T., II; Afshari, C.A.; Hamadeh, H.K. A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Toxicol. Sci., 2013, 136, 216-241.
[106]
Pedersen, J.M.; Matsson, P.; Bergstrom, C.A.; Hoogstraate, J.; Noren, A.; LeCluyse, E.L.; Artursson, P. Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol. Sci., 2013, 136, 328-343.
[107]
Yang, K.; Woodhead, J.L.; Watkins, P.B.; Howell, B.A.; Brouwer, K.L. Systems pharmacology modeling predicts delayed presentation and species differences in bile acid-mediated troglitazone hepatotoxicity. Clin. Pharmacol. Ther., 2014, 96, 589-598.
[108]
Newsome, P.N.; Johannessen, I.; Boyle, S.; Dalakas, E.; McAulay, K.A.; Samuel, K.; Rae, F.; Forrester, L.; Turner, M.L.; Hayes, P.C.; Harrison, D.J.; Bickmore, W.A.; Plevris, J.N. Human cord blood-derived cells can differentiate into hepatocytes in the mouse liver with no evidence of cellular fusion. Gastroenterology, 2003, 124, 1891-1900.
[109]
Peters, R.; Wolf, M.J.; Van Den Broek, M.; Nuvolone, M.; Dannenmann, S.; Stieger, B.; Rapold, R.; Konrad, D.; Rubin, A.; Bertino, J.R.; Aguzzi, A.; Heikenwalder, M.; Knuth, A.K. Efficient generation of multipotent mesenchymal stem cells from umbilical cord blood in stroma-free liquid culture. PLoS One, 2010, 5, e15689.
[110]
Ghodsizadeh, A.; Taei, A.; Totonchi, M.; Seifinejad, A.; Gourabi, H.; Pournasr, B.; Aghdami, N.; Malekzadeh, R.; Almadani, N.; Salekdeh, G.H.; Baharvand, H. Generation of liver disease-specific induced pluripotent stem cells along with efficient differentiation to functional hepatocyte-like cells. Stem Cell Rev., 2010, 6, 622-632.
[111]
Rashid, S.T.; Corbineau, S.; Hannan, N.; Marciniak, S.J.; Miranda, E.; Alexander, G.; Huang-Doran, I.; Griffin, J.; Ahrlund-Richter, L.; Skepper, J.; Semple, R.; Weber, A.; Lomas, D.A.; Vallier, L. Modeling inherited metabolic disorders of the liver using human induced pluripotent stem cells. J. Clin. Invest., 2010, 120, 3127-3136.
[112]
Asgari, S.; Pournasr, B.; Salekdeh, G.H.; Ghodsizadeh, A.; Ott, M.; Baharvand, H. Induced pluripotent stem cells: A new era for hepatology. J. Hepatol., 2010, 4, 738-751.


Rights & PermissionsPrintExport Cite as


Article Details

VOLUME: 20
ISSUE: 5
Year: 2019
Page: [377 - 389]
Pages: 13
DOI: 10.2174/1389200220666190426152830
Price: $58

Article Metrics

PDF: 18
HTML: 5