Hepatic overexpression of caveolins increases bile salt secretion in mice

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dc.contributor.authorMoreno, M
dc.contributor.authorMolina, H
dc.contributor.authorAmigo, L
dc.contributor.authorZanlungo, S
dc.contributor.authorArrese, M
dc.contributor.authorRigotti, A
dc.contributor.authorMiquel, JF
dc.date.accessioned2024-01-10T12:05:47Z
dc.date.available2024-01-10T12:05:47Z
dc.date.issued2003
dc.description.abstractCaveolins are cholesterol-binding proteins involved in the regulation of several intracellular processes, including cholesterol transport. Because hepatocytes express caveolin-1 and caveolin-2, these proteins might modulate hepatic lipid metabolism and biliary lipid secretion. Our aim was to investigate the potential physiologic role of caveolins in hepatic cholesterol and bile salt (BS) metabolism and transport using adenoviral gene transfer. C57BL/6 mice were infected with recombinant human caveolin-1 and caveolin-2 adenoviruses. Mice infected with adenovirus lacking the transgene were used as controls. Hepatic caveolin expression was evaluated by immunochemical methods. Reverse-transcription polymerase chain reaction (RT-PCR) and immunoblotting were used to assess messenger RNA (mRNA) levels and protein mass of BS transporters (sodium taurocholate cotransporting polypeptide [Ntcp] and bile salt export pump [Bsep]). Serum, liver, biliary, and fecal biochemical determinations and BS maximal secretory rate (SRm) were performed by standard methods. Ad.Cav-1- and Ad.Cav-2-infected mice exhibited a 10- and 7-fold increase in hepatic caveolin-1 and caveolin-2 protein expression, respectively. Caveolin-1-overexpressing mice had a significant increase in plasma high-density lipoprotein (HDL) cholesterol and hepatic free cholesterol content, whereas total plasma cholesterol and triglyceride levels remained unchanged. Hepatic caveolin-1 and/or caveolin-2 overexpression significantly increased bile flow and secretion of all biliary lipids. Caveolin-1-overexpressing mice showed a 2.5-fold increase in taurocholate (TC) SRm, indicating increased canalicular BS transport capacity. BS pool size and fecal BS excretion remained within the normal range in mice with Cav-1 overexpression. No changes were seen in the protein mass of BS transporters NtcP and Bsep. In conclusion, our findings indicate that caveolins may play an important role in regulating hepatic BS and cholesterol metabolism.
dc.fechaingreso.objetodigital25-03-2024
dc.format.extent12 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.hep.2003.09.011
dc.identifier.eissn1527-3350
dc.identifier.issn0270-9139
dc.identifier.pubmedidMEDLINE:14647059
dc.identifier.urihttps://doi.org/10.1016/j.hep.2003.09.011
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/76069
dc.identifier.wosidWOS:000187032100019
dc.information.autorucMedicina;Arrese M;S/I;76095
dc.information.autorucMedicina;Miquel J;S/I;72216
dc.information.autorucMedicina;Rigotti A;S/I;68489
dc.information.autorucMedicina;Zanlungo S;S/I;72650
dc.issue.numero6
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final1488
dc.pagina.inicio1477
dc.publisherWILEY
dc.revistaHEPATOLOGY
dc.rightsacceso restringido
dc.subjectBILIARY CHOLESTEROL SECRETION
dc.subjectDENSITY-LIPOPROTEIN RECEPTOR
dc.subjectRAT-LIVER
dc.subjectPLASMA-MEMBRANE
dc.subjectEXPORT PUMP
dc.subjectSIGNAL-TRANSDUCTION
dc.subjectPROTEIN EXPRESSION
dc.subjectDOWN-REGULATION
dc.subjectSHOW EVIDENCE
dc.subjectUP-REGULATION
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleHepatic overexpression of caveolins increases bile salt secretion in mice
dc.typeartículo
dc.volumen38
sipa.codpersvinculados76095
sipa.codpersvinculados72216
sipa.codpersvinculados68489
sipa.codpersvinculados72650
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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