Induction of the multispecific organic anion transporter (cMoat/mrp2) gene and biliary glutathione secretion by the herbicide 2,4,5-trichlorophenoxyacetic acid in the mouse liver

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dc.contributor.authorWielandt, AM
dc.contributor.authorVollrath, V
dc.contributor.authorManzano, M
dc.contributor.authorMiranda, S
dc.contributor.authorAccatino, L
dc.contributor.authorChianale, J
dc.date.accessioned2024-01-10T12:06:02Z
dc.date.available2024-01-10T12:06:02Z
dc.date.issued1999
dc.description.abstractThe canalicular multispecific organic anion transporter. cMoat, is an ATP-binding-cassette protein expressed in the canalicular domain of hepatocytes. In addition to the transport of endo- and xenobiotics, cMoat has also been proposed to transport GSH into bile, the major driving force of bile-acid-independent bile flow. We have shown previously that the herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), a peroxisome-proliferator agent, significantly increases bile-acid-independent bile flow in mice. On this basis, the effect of the herbicide on cMoat gene expression was studied. A 3.6-fold increase in cMoat mRNA levels and a 2.5-fold increase in cMoat protein content were observed in the liver of mice fed on a diet supplemented with 0.125% 2,4,5-T. These effects were due to an increased rate of gene transcription (3.9-fold) and were not associated with peroxisome proliferation. Significant increases in bile flow (2.23 +/- 0.39 versus 1.13 +/- 0.15 mu l/min per g of liver: P < 0.05) and biliary GSH output (7.40 +/- 3.30 versus 2.65 +/- 0.34 nmol/min per g of liver; P < 0.05) were observed in treated animals. The hepatocellular concentration of total glutathione also increased in hepatocytes of treated mice (10.95 +/- 0.84 versus 5.12 +/- 0.47 mM; P < 0.05), because of the induction (2.4-fold) of the heavy subunit of the gamma-glutamylcysteine synthetase (GCS-HS) gene. This is the first model of co-induction of cMoat and GCS-HS genes in vivo in the mouse liver, associated with increased glutathione synthesis and biliary glutathione output. Our observations are consistent with the hypothesis that the cMoat transporter plays a crucial role in the secretion of biliary GSH.
dc.fechaingreso.objetodigital2024-05-02
dc.format.extent7 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1042/0264-6021:3410105
dc.identifier.issn0264-6021
dc.identifier.pubmedidMEDLINE:10377250
dc.identifier.urihttps://doi.org/10.1042/0264-6021:3410105
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/76104
dc.identifier.wosidWOS:000081468800014
dc.information.autorucMedicina;Accatino L;S/I;99016
dc.information.autorucMedicina;Chianale J;S/I;99780
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final111
dc.pagina.inicio105
dc.publisherPORTLAND PRESS
dc.revistaBIOCHEMICAL JOURNAL
dc.rightsacceso restringido
dc.subjectABC transporter
dc.subjectbile flow
dc.subjectcanalicular transport
dc.subjectgamma-glutamylcysteine synthetase heavy-subunit gene
dc.subjectxenobiotics
dc.subjectGAMMA-GLUTAMYLCYSTEINE SYNTHETASE
dc.subjectHEPATOCYTE CANALICULAR ISOFORM
dc.subjectMULTIDRUG-RESISTANCE PROTEIN
dc.subjectATP-DEPENDENT TRANSPORT
dc.subjectCMRP/CMOAT GENE
dc.subjectMESSENGER-RNA
dc.subjectMUTANT RATS
dc.subjectMDR2 GENE
dc.subjectEXPRESSION
dc.subjectCONJUGATE
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleInduction of the multispecific organic anion transporter (cMoat/mrp2) gene and biliary glutathione secretion by the herbicide 2,4,5-trichlorophenoxyacetic acid in the mouse liver
dc.typeartículo
dc.volumen341
sipa.codpersvinculados99016
sipa.codpersvinculados99780
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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