Molecular regulation of the hepatic bile acid uptake transporter and HBV entry receptor NTCP
Transporters expressed by hepatocytes and enterocytes play a critical role in maintaining the enterohepatic circulation of bile acids. The sodium taurocholate cotransporting polypeptide (NTCP), exclusively expressed at the basolateral side of hepatocytes, mediates the uptake of conjugated bile acids...
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| Veröffentlicht in: | Biochimica et biophysica acta. Molecular and cell biology of lipids 2021-08, Vol.1866 (8), p.158960, Article 158960 |
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| container_title | Biochimica et biophysica acta. Molecular and cell biology of lipids |
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| creator | Appelman, Monique D. Wettengel, Jochen M. Protzer, Ulrike Oude Elferink, Ronald P.J. van de Graaf, Stan F.J. |
| description | Transporters expressed by hepatocytes and enterocytes play a critical role in maintaining the enterohepatic circulation of bile acids. The sodium taurocholate cotransporting polypeptide (NTCP), exclusively expressed at the basolateral side of hepatocytes, mediates the uptake of conjugated bile acids. In conditions where bile flow is impaired (cholestasis), pharmacological inhibition of NTCP-mediated bile acid influx is suggested to reduce hepatocellular damage due to bile acid overload. Furthermore, NTCP has been shown to play an important role in hepatitis B virus (HBV) and hepatitis Delta virus (HDV) infection by functioning as receptor for viral entry into hepatocytes. This review provides a summary of current molecular insight into the regulation of NTCP expression at the plasma membrane, hepatic bile acid transport, and NTCP-mediated viral infection.
•Complementary mechanisms exist to downregulate bile acid uptake during cholestasis.•Pharmacological NTCP inhibition is hepatoprotective in cholestasis.•HBV/HDV entry requires NTCP and can be inhibited by a pre-S1 mimicking peptide.•Inhibition of NTCP could be beneficial in metabolic disorders. |
| doi_str_mv | 10.1016/j.bbalip.2021.158960 |
| format | Article |
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•Complementary mechanisms exist to downregulate bile acid uptake during cholestasis.•Pharmacological NTCP inhibition is hepatoprotective in cholestasis.•HBV/HDV entry requires NTCP and can be inhibited by a pre-S1 mimicking peptide.•Inhibition of NTCP could be beneficial in metabolic disorders.</description><identifier>ISSN: 1388-1981</identifier><identifier>ISSN: 1879-2618</identifier><identifier>EISSN: 1879-2618</identifier><identifier>DOI: 10.1016/j.bbalip.2021.158960</identifier><identifier>PMID: 33932583</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; ASBT ; Bile Acids and Salts - metabolism ; Biological Transport ; BSEP ; Cholestasis ; HBV ; HDV ; Hepatitis B - metabolism ; Hepatitis B - virology ; Hepatitis B virus - metabolism ; Hepatitis B virus - physiology ; Hepatitis Delta Virus - genetics ; Hepatitis Delta Virus - metabolism ; Hepatitis Delta Virus - physiology ; Hepatocytes - metabolism ; Hepatocytes - virology ; Humans ; Liver - metabolism ; Liver - virology ; Organic Anion Transporters, Sodium-Dependent - genetics ; Organic Anion Transporters, Sodium-Dependent - metabolism ; Symporters - genetics ; Symporters - metabolism ; Virus Internalization</subject><ispartof>Biochimica et biophysica acta. Molecular and cell biology of lipids, 2021-08, Vol.1866 (8), p.158960, Article 158960</ispartof><rights>2021 The Author(s)</rights><rights>Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-2e5eff3365ca03a3c4a1f5fe9738970296ab4289af7baf6ff0a00f51e6c459693</citedby><cites>FETCH-LOGICAL-c474t-2e5eff3365ca03a3c4a1f5fe9738970296ab4289af7baf6ff0a00f51e6c459693</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbalip.2021.158960$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33932583$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Appelman, Monique D.</creatorcontrib><creatorcontrib>Wettengel, Jochen M.</creatorcontrib><creatorcontrib>Protzer, Ulrike</creatorcontrib><creatorcontrib>Oude Elferink, Ronald P.J.</creatorcontrib><creatorcontrib>van de Graaf, Stan F.J.</creatorcontrib><title>Molecular regulation of the hepatic bile acid uptake transporter and HBV entry receptor NTCP</title><title>Biochimica et biophysica acta. Molecular and cell biology of lipids</title><addtitle>Biochim Biophys Acta Mol Cell Biol Lipids</addtitle><description>Transporters expressed by hepatocytes and enterocytes play a critical role in maintaining the enterohepatic circulation of bile acids. The sodium taurocholate cotransporting polypeptide (NTCP), exclusively expressed at the basolateral side of hepatocytes, mediates the uptake of conjugated bile acids. In conditions where bile flow is impaired (cholestasis), pharmacological inhibition of NTCP-mediated bile acid influx is suggested to reduce hepatocellular damage due to bile acid overload. Furthermore, NTCP has been shown to play an important role in hepatitis B virus (HBV) and hepatitis Delta virus (HDV) infection by functioning as receptor for viral entry into hepatocytes. This review provides a summary of current molecular insight into the regulation of NTCP expression at the plasma membrane, hepatic bile acid transport, and NTCP-mediated viral infection.
•Complementary mechanisms exist to downregulate bile acid uptake during cholestasis.•Pharmacological NTCP inhibition is hepatoprotective in cholestasis.•HBV/HDV entry requires NTCP and can be inhibited by a pre-S1 mimicking peptide.•Inhibition of NTCP could be beneficial in metabolic disorders.</description><subject>Animals</subject><subject>ASBT</subject><subject>Bile Acids and Salts - metabolism</subject><subject>Biological Transport</subject><subject>BSEP</subject><subject>Cholestasis</subject><subject>HBV</subject><subject>HDV</subject><subject>Hepatitis B - metabolism</subject><subject>Hepatitis B - virology</subject><subject>Hepatitis B virus - metabolism</subject><subject>Hepatitis B virus - physiology</subject><subject>Hepatitis Delta Virus - genetics</subject><subject>Hepatitis Delta Virus - metabolism</subject><subject>Hepatitis Delta Virus - physiology</subject><subject>Hepatocytes - metabolism</subject><subject>Hepatocytes - virology</subject><subject>Humans</subject><subject>Liver - metabolism</subject><subject>Liver - virology</subject><subject>Organic Anion Transporters, Sodium-Dependent - genetics</subject><subject>Organic Anion Transporters, Sodium-Dependent - metabolism</subject><subject>Symporters - genetics</subject><subject>Symporters - metabolism</subject><subject>Virus Internalization</subject><issn>1388-1981</issn><issn>1879-2618</issn><issn>1879-2618</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEtP3DAQx60KVB7tN6iQj1yy9SNO7EslWLVdJB49AKdKluOMi5dsHGwHiW9fo9AeOc2M9H9ofgh9oWRFCW2-blddZwY_rRhhdEWFVA35gA6pbFXFGir3ys6lrKiS9AAdpbQlhArOxUd0wLniTEh-iH5fhQHsPJiII_wpM_sw4uBwfgD8AFO5Le78ANhY3-N5yuYRcI5mTFOIGSI2Y4835_cYxhxfSoiFKYeIr2_Xvz6hfWeGBJ_f5jG6-_H9dr2pLm9-XqzPLitbt3WuGAhwjvNGWEO44bY21AkHquVStYSpxnQ1k8q4tjOucY4YQpyg0NhaqEbxY3S65E4xPM2Qst75ZGEYzAhhTpoJRqQglNIirRepjSGlCE5P0e9MfNGU6FeueqsXrvqVq164FtvJW8Pc7aD_b_oHsgi-LQIofz57iDpZD6OF3hckWffBv9_wFzU5iuQ</recordid><startdate>202108</startdate><enddate>202108</enddate><creator>Appelman, Monique D.</creator><creator>Wettengel, Jochen M.</creator><creator>Protzer, Ulrike</creator><creator>Oude Elferink, Ronald P.J.</creator><creator>van de Graaf, Stan F.J.</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202108</creationdate><title>Molecular regulation of the hepatic bile acid uptake transporter and HBV entry receptor NTCP</title><author>Appelman, Monique D. ; Wettengel, Jochen M. ; Protzer, Ulrike ; Oude Elferink, Ronald P.J. ; van de Graaf, Stan F.J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-2e5eff3365ca03a3c4a1f5fe9738970296ab4289af7baf6ff0a00f51e6c459693</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>ASBT</topic><topic>Bile Acids and Salts - metabolism</topic><topic>Biological Transport</topic><topic>BSEP</topic><topic>Cholestasis</topic><topic>HBV</topic><topic>HDV</topic><topic>Hepatitis B - metabolism</topic><topic>Hepatitis B - virology</topic><topic>Hepatitis B virus - metabolism</topic><topic>Hepatitis B virus - physiology</topic><topic>Hepatitis Delta Virus - genetics</topic><topic>Hepatitis Delta Virus - metabolism</topic><topic>Hepatitis Delta Virus - physiology</topic><topic>Hepatocytes - metabolism</topic><topic>Hepatocytes - virology</topic><topic>Humans</topic><topic>Liver - metabolism</topic><topic>Liver - virology</topic><topic>Organic Anion Transporters, Sodium-Dependent - genetics</topic><topic>Organic Anion Transporters, Sodium-Dependent - metabolism</topic><topic>Symporters - genetics</topic><topic>Symporters - metabolism</topic><topic>Virus Internalization</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Appelman, Monique D.</creatorcontrib><creatorcontrib>Wettengel, Jochen M.</creatorcontrib><creatorcontrib>Protzer, Ulrike</creatorcontrib><creatorcontrib>Oude Elferink, Ronald P.J.</creatorcontrib><creatorcontrib>van de Graaf, Stan F.J.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Biochimica et biophysica acta. Molecular and cell biology of lipids</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Appelman, Monique D.</au><au>Wettengel, Jochen M.</au><au>Protzer, Ulrike</au><au>Oude Elferink, Ronald P.J.</au><au>van de Graaf, Stan F.J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molecular regulation of the hepatic bile acid uptake transporter and HBV entry receptor NTCP</atitle><jtitle>Biochimica et biophysica acta. Molecular and cell biology of lipids</jtitle><addtitle>Biochim Biophys Acta Mol Cell Biol Lipids</addtitle><date>2021-08</date><risdate>2021</risdate><volume>1866</volume><issue>8</issue><spage>158960</spage><pages>158960-</pages><artnum>158960</artnum><issn>1388-1981</issn><issn>1879-2618</issn><eissn>1879-2618</eissn><abstract>Transporters expressed by hepatocytes and enterocytes play a critical role in maintaining the enterohepatic circulation of bile acids. The sodium taurocholate cotransporting polypeptide (NTCP), exclusively expressed at the basolateral side of hepatocytes, mediates the uptake of conjugated bile acids. In conditions where bile flow is impaired (cholestasis), pharmacological inhibition of NTCP-mediated bile acid influx is suggested to reduce hepatocellular damage due to bile acid overload. Furthermore, NTCP has been shown to play an important role in hepatitis B virus (HBV) and hepatitis Delta virus (HDV) infection by functioning as receptor for viral entry into hepatocytes. This review provides a summary of current molecular insight into the regulation of NTCP expression at the plasma membrane, hepatic bile acid transport, and NTCP-mediated viral infection.
•Complementary mechanisms exist to downregulate bile acid uptake during cholestasis.•Pharmacological NTCP inhibition is hepatoprotective in cholestasis.•HBV/HDV entry requires NTCP and can be inhibited by a pre-S1 mimicking peptide.•Inhibition of NTCP could be beneficial in metabolic disorders.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>33932583</pmid><doi>10.1016/j.bbalip.2021.158960</doi><oa>free_for_read</oa></addata></record> |
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| ispartof | Biochimica et biophysica acta. Molecular and cell biology of lipids, 2021-08, Vol.1866 (8), p.158960, Article 158960 |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Animals ASBT Bile Acids and Salts - metabolism Biological Transport BSEP Cholestasis HBV HDV Hepatitis B - metabolism Hepatitis B - virology Hepatitis B virus - metabolism Hepatitis B virus - physiology Hepatitis Delta Virus - genetics Hepatitis Delta Virus - metabolism Hepatitis Delta Virus - physiology Hepatocytes - metabolism Hepatocytes - virology Humans Liver - metabolism Liver - virology Organic Anion Transporters, Sodium-Dependent - genetics Organic Anion Transporters, Sodium-Dependent - metabolism Symporters - genetics Symporters - metabolism Virus Internalization |
| title | Molecular regulation of the hepatic bile acid uptake transporter and HBV entry receptor NTCP |
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