EFFECT OF COLCHICINE AND HEAT-SHOCK ON MULTIDRUG-RESISTANCE GENE AND P-GLYCOPROTEIN EXPRESSION IN RAT-LIVER

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dc.contributor.authorVOLLRATH, V
dc.contributor.authorWIELANDT, AM
dc.contributor.authorACUNA, C
dc.contributor.authorDUARTE, I
dc.contributor.authorANDRADE, L
dc.contributor.authorCHIANALE, J
dc.date.accessioned2024-01-10T13:47:50Z
dc.date.available2024-01-10T13:47:50Z
dc.date.issued1994
dc.description.abstractThe multidrug resistance genes encode plasma membrane glycoproteins named P-glycoproteins, that act as an ATP-dependent drug efflux pump and decrease the cytosolic concentration of chemotherapeutic agents. It has been hypothesized that in rat liver, this protein may have a physiological role as a biliary transporter of xenobiotics and endobiotics. Some human tumor cell lines turn on the human multidrug resistance gene in response to high temperature and after exposure to toxic chemicals. Accordingly, it has been proposed that the human multidrug resistance gene is a heat shock gene. We have assessed whether two environmental stresses, heat shock or acute exposure to cytotoxic drugs (colchicine, vincristine, vinblastine and daunomycin), induce changes in the expression of multidrug resistance genes in the rat. Total cellular RNA extracted from rat liver was hybridized to a labeled human multidrug resistance gene cDNA probe. Temperature upshift did not increase the steady-state of mdf mRNA levels in the tissues studied, suggesting that the mdr genes are not activated as part of a heat shock response. The mdi mRNA levels increased in rat liver as early as 3 h after a single injection of colchicine, reached a peak (500%; p<0.05) after around 24 h and returned to constitutive levels after 48 h. Changes in the relative content of mdr mRNA were not detected in kidney, adrenal gland and small bowel, suggesting that the in vivo induction of the mdr gene in the liver is a tissue-specific response. The other cytotoxic drugs that were tested did not increase the steady-state of mdr mRNA levels. Using specific PCR-generated mouse mdr cDNA probes, we found that only the mdr 2 gene is overexpressed in the liver of colchicine-treated mouse. The mdr gene induction was followed at 48-72 h by a stronger immunostaining in rat liver of its encoded product, suggesting that the newly synthesized protein was incorporated into the canalicular domain of hepatocytes. This is the first evidence of modulation of mdr expression gene in rodent liver in response to colchicine, a substrate of P-glycoprotein in multidrug resistant cells. (C) Journal of Hepatology.
dc.fechaingreso.objetodigital16-04-2024
dc.format.extent10 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1016/S0168-8278(94)80235-1
dc.identifier.eissn1600-0641
dc.identifier.issn0168-8278
dc.identifier.pubmedidMEDLINE:7890890
dc.identifier.urihttps://doi.org/10.1016/S0168-8278(94)80235-1
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/79308
dc.identifier.wosidWOS:A1994PV81600011
dc.information.autorucMedicina;Chianale J;S/I;99780
dc.issue.numero5
dc.language.isoen
dc.nota.accesoContenido parcial
dc.pagina.final763
dc.pagina.inicio754
dc.publisherELSEVIER SCIENCE BV
dc.revistaJOURNAL OF HEPATOLOGY
dc.rightsacceso restringido
dc.subjectCOLCHICINE
dc.subjectHEAT SHOCK
dc.subjectINDUCTION
dc.subjectMDR GENE FAMILY
dc.subjectP-GLYCOPROTEIN
dc.subjectXENOBIOTICS
dc.subjectCELL-LINES
dc.subjectHEPATOCELLULAR CARCINOMAS
dc.subjectCANALICULAR MEMBRANE
dc.subjectFAMILY
dc.subjectBILE
dc.subjectPROTEINS
dc.subjectOVEREXPRESSION
dc.subjectAMPLIFICATION
dc.subjectTISSUES
dc.subjectVINBLASTINE
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleEFFECT OF COLCHICINE AND HEAT-SHOCK ON MULTIDRUG-RESISTANCE GENE AND P-GLYCOPROTEIN EXPRESSION IN RAT-LIVER
dc.typeartículo
dc.volumen21
sipa.codpersvinculados99780
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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