Fibrates induce mdr2 gene expression and biliary phospholipid secretion in the mouse

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dc.contributor.authorChianale, J
dc.contributor.authorVollrath, V
dc.contributor.authorWielandt, AM
dc.contributor.authorAmigo, L
dc.contributor.authorRigotti, A
dc.contributor.authorNervi, F
dc.contributor.authorGonzalez, S
dc.contributor.authorAndrade, L
dc.contributor.authorPizarro, M
dc.contributor.authorAccatino, L
dc.date.accessioned2024-01-10T12:38:59Z
dc.date.available2024-01-10T12:38:59Z
dc.date.issued1996
dc.description.abstractDisruption of the murine mdr2 gene leads to the complete absence of biliary phospholipids. We tested the hypothesis that the increase in biliary phospholipid output induced by fibrates is mediated via induction of the hepatic mdr2 gene and its encoded product, the P-glycoprotein canalicular flippase. Increased levels of mdr2 mRNA were observed in the liver of mice treated with different fibrates: ciprofibrate, 660+/-155% (as compared with control group); clofibrate, 611+/-77 %; bezafibrate, 410+/-47 %; fenofibrate, 310+/-52 %; gemfibrozil, 190+/-25 % (P < 0.05 compared with control group). Induction of expression of the mdr gene family was specific to the mdr2 gene. Two- to three-fold increases in P-glycoprotein immunodetection were evident on the canalicular plasma-membrane domain of clofibrate- and ciprofibrate-treated mice. Biliary phospholipid output increased from 4.2+/-1.2 nmol/min per g of liver in the control group to 8.5+/-0.6, 7.1+/-2.9 and 5.8+/-2.5 in ciprofibrate-, clofibrate- and bezafibrate-treated mice respectively (P < 0.05 compared with control group). Moreover, a significant correlation between biliary phospholipid output and the relative levels of mdr2 mRNA was found (r = 0.86; P < 0.05). In treated animals, bile flow as well as cholesterol and bile acid outputs remained unchanged. Our findings constitute the first evidence that pharmacological modulation of biliary lipid secretion mediated by fibrates can be related to the overexpression of a specific liver gene product, the mdr2 P-glycoprotein, and are consistent with the hypothesis that the mdr2 P-glycoprotein isoform plays a crucial role in the secretion of biliary phospholipid.
dc.fechaingreso.objetodigital2024-05-02
dc.format.extent6 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1042/bj3140781
dc.identifier.eissn1470-8728
dc.identifier.issn0264-6021
dc.identifier.pubmedidMEDLINE:8615769
dc.identifier.urihttps://doi.org/10.1042/bj3140781
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/77129
dc.identifier.wosidWOS:A1996UC24500010
dc.information.autorucMedicina;Accatino L;S/I;99016
dc.information.autorucMedicina;Chianale J;S/I;99780
dc.information.autorucMedicina;González S;S/I;99856
dc.information.autorucMedicina;Nervi F;S/I;99156
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final786
dc.pagina.inicio781
dc.publisherPORTLAND PRESS LTD
dc.revistaBIOCHEMICAL JOURNAL
dc.rightsacceso restringido
dc.subjectMULTIDRUG-RESISTANCE GENE
dc.subjectP-GLYCOPROTEIN
dc.subjectCANALICULAR MEMBRANE
dc.subjectRAT-LIVER
dc.subjectBILE
dc.subjectANTIBODIES
dc.subjectTISSUES
dc.subjectFAMILY
dc.subjectSEQUENCE
dc.subjectPRIMATES
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleFibrates induce mdr2 gene expression and biliary phospholipid secretion in the mouse
dc.typeartículo
dc.volumen314
sipa.codpersvinculados99016
sipa.codpersvinculados99780
sipa.codpersvinculados99856
sipa.codpersvinculados99156
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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