Bucillamine induces glutathione biosynthesis via activation of the transcription factor Nrf2

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dc.contributor.authorWielandt, Ana M.
dc.contributor.authorVollrath, Valeska
dc.contributor.authorFarias, Marcelo
dc.contributor.authorChianale, Jose
dc.date.accessioned2024-01-10T12:04:31Z
dc.date.available2024-01-10T12:04:31Z
dc.date.issued2006
dc.description.abstractThe properties of bucillamine, a synthetic antioxidant, have been attributed mainly to the donation of thiol groups to glutathione (GSH). We recently demonstrated that glutamatecysteine ligase catalytic subunit (GCLC), the rate-limiting enzyme of GSH biosynthesis, and the multidrug-resistance-associated protein 2 (Mrp2/MRP2) are coordinately induced in response to xenobiotic through the activation of the antioxidant-response element (ARE) by nuclear factor-erythroid 2 p45-related factor (Nrf2). We tested the hypothesis that bucillamine and its oxidized metabolite SA 981 also activate the Nrf2 pathway, thereby increasing glutathione biosynthesis in human HepG2 and murine Hepa 1-6 hepatoma cell lines, through the induction of the GCLC enzyme as well as the Mrp2/MRP2 transporter, which mediates the excretion of glutathione and its conjugates from hepatocytes. Both bucillamine and SA 981 produced a significant dose-dependent increase in the mRNA levels of Mrp2/MRP2 and GCLC after 24 h. The levels of the transcription factor Nrf2 in the nuclei were maximal at 3 h, remained elevated at 6 h, and decreased to control values at 24 h in both cell lines. Moreover, both bucillamine and SA 981 significantly increased the expressions of Mrp2/MRP2 and GCLC proteins in both cell lines. Finally, in both cell lines, bucillamine and SA 981 increased the GSH content two- to three-fold. These results demonstrate that bucillamine and SA 981 activate the ARE-ARE pathway increasing the expression of ARE-driven genes such as those of GCLC and Mrp2/MRP2. The role of bucillamine as a chemopreventive agent against cancer remains to be elucidated. (c) 2006 Elsevier Inc. All rights reserved.
dc.fechaingreso.objetodigital20-03-2024
dc.format.extent8 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.bcp.2006.05.011
dc.identifier.issn0006-2952
dc.identifier.pubmedidMEDLINE:16806086
dc.identifier.urihttps://doi.org/10.1016/j.bcp.2006.05.011
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/75821
dc.identifier.wosidWOS:000239641600007
dc.information.autorucMedicina;Chianale J;S/I;99780
dc.information.autorucMedicina;Farías M;S/I;12286
dc.information.autorucMedicina;Vollrath V;S/I;2185
dc.information.autorucMedicina;Wielandt AM;S/I;70653
dc.issue.numero4
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final462
dc.pagina.inicio455
dc.publisherPERGAMON-ELSEVIER SCIENCE LTD
dc.revistaBIOCHEMICAL PHARMACOLOGY
dc.rightsacceso restringido
dc.subjectbucillamine
dc.subjectglutamate-cysteine ligase (GCL)
dc.subjectmultidrug-resistance associated protein 2(Mrp2/MRP2)
dc.subjectglutathione (GSH)
dc.subjectnuclear factor-erythroid 2 p45-related factor (Nrf2)
dc.subjectGAMMA-GLUTAMYLCYSTEINE SYNTHETASE
dc.subjectGENE-EXPRESSION
dc.subjectINDUCIBLE EXPRESSION
dc.subjectCHEMOPREVENTIVE COMPOUNDS
dc.subjectREPERFUSION INJURY
dc.subjectSUBUNIT GENE
dc.subjectANTIOXIDANT
dc.subjectINDUCTION
dc.subjectDRUG
dc.subjectMICE
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleBucillamine induces glutathione biosynthesis via activation of the transcription factor Nrf2
dc.typeartículo
dc.volumen72
sipa.codpersvinculados99780
sipa.codpersvinculados12286
sipa.codpersvinculados2185
sipa.codpersvinculados70653
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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