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dc.contributor.authorSchonhoff, Christopher M.
dc.contributor.authorThankey, Krishna
dc.contributor.authorWebster, Cynthia R. L.
dc.contributor.authorWakabayashi, Yoshiyuki
dc.contributor.authorWolkoff, Allan W.
dc.contributor.authorAnwer, M. Sawkat
dc.date2022-08-11T08:08:52.000
dc.date.accessioned2022-08-23T16:10:50Z
dc.date.available2022-08-23T16:10:50Z
dc.date.issued2008-08-09
dc.date.submitted2009-02-25
dc.identifier.citationHepatology. 2008 Nov;48(5):1665-70. <a href="http://dx.doi.org/10.1002/hep.22495">Link to article on publisher's site</a>
dc.identifier.issn1527-3350 (Electronic)
dc.identifier.doi10.1002/hep.22495
dc.identifier.pmid18688880
dc.identifier.pmid18688880
dc.identifier.urihttp://hdl.handle.net/20.500.14038/33027
dc.description.abstractCyclic adenosine monophosphate (cAMP) stimulates hepatic bile acid uptake by translocating sodium-taurocholate (TC) cotransporting polypeptide (Ntcp) from an endosomal compartment to the plasma membrane. Rab4 is associated with early endosomes and involved in vesicular trafficking. This study was designed to determine the role of Rab4 in cAMP-induced TC uptake and Ntcp translocation. HuH-Ntcp cells transiently transfected with empty vector, guanosine triphosphate (GTP) locked dominant active Rab4 (Rab4(GTP)), or guanosine diphosphate (GDP) locked dominant inactive Rab4 (Rab4(GDP)) were used to study the role of Rab4. Neither Rab4(GTP) nor Rab4(GDP) affected either basal TC uptake or plasma membrane Ntcp level. However, cAMP-induced increases in TC uptake and Ntcp translocation were enhanced by Rab4(GTP) and inhibited by Rab4(GDP). In addition, cAMP increased GTP binding to endogenous Rab4 in a time-dependent, but phosphoinositide-3-kinase-independent manner. CONCLUSION: Taken together, these results suggest that cAMP-mediated phosphoinositide-3-kinase-independent activation of Rab4 facilitates Ntcp translocation in HuH-Ntcp cells.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=18688880&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1002/hep.22495
dc.subjectBile Acids and Salts; Biological Transport; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Membrane; Cyclic AMP; Endosomes; Humans; Liver Neoplasms; Organic Anion Transporters, Sodium-Dependent; Protein Transport; Symporters; Transfection; rab4 GTP-Binding Proteins
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleRab4 facilitates cyclic adenosine monophosphate-stimulated bile acid uptake and Na+-taurocholate cotransporting polypeptide translocation
dc.typeJournal Article
dc.source.journaltitleHepatology (Baltimore, Md.)
dc.source.volume48
dc.source.issue5
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/1575
dc.identifier.contextkey740114
html.description.abstract<p>Cyclic adenosine monophosphate (cAMP) stimulates hepatic bile acid uptake by translocating sodium-taurocholate (TC) cotransporting polypeptide (Ntcp) from an endosomal compartment to the plasma membrane. Rab4 is associated with early endosomes and involved in vesicular trafficking. This study was designed to determine the role of Rab4 in cAMP-induced TC uptake and Ntcp translocation. HuH-Ntcp cells transiently transfected with empty vector, guanosine triphosphate (GTP) locked dominant active Rab4 (Rab4(GTP)), or guanosine diphosphate (GDP) locked dominant inactive Rab4 (Rab4(GDP)) were used to study the role of Rab4. Neither Rab4(GTP) nor Rab4(GDP) affected either basal TC uptake or plasma membrane Ntcp level. However, cAMP-induced increases in TC uptake and Ntcp translocation were enhanced by Rab4(GTP) and inhibited by Rab4(GDP). In addition, cAMP increased GTP binding to endogenous Rab4 in a time-dependent, but phosphoinositide-3-kinase-independent manner. CONCLUSION: Taken together, these results suggest that cAMP-mediated phosphoinositide-3-kinase-independent activation of Rab4 facilitates Ntcp translocation in HuH-Ntcp cells.</p>
dc.identifier.submissionpathgsbs_sp/1575
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology
dc.contributor.departmentGraduate School of Biomedical Sciences
dc.source.pages1665-70


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