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dc.contributor.author
Ghanem, Carolina Inés
dc.contributor.author
Rudraiah, Swetha
dc.contributor.author
Bataille, Amy M.
dc.contributor.author
Vigo, María B.
dc.contributor.author
Goedken, Michael J.
dc.contributor.author
Manautou, José E.
dc.date.available
2017-03-08T21:55:47Z
dc.date.issued
2015-04
dc.identifier.citation
Ghanem, Carolina Inés; Rudraiah, Swetha; Bataille, Amy M.; Vigo, María B.; Goedken, Michael J.; et al.; Role of nuclear factor-erythroid 2-related factor 2 (Nrf2) in the transcriptional regulation of brain ABC transporters during acute acetaminophen (APAP) intoxication in mice; Elsevier Inc; Biochemical Pharmacology; 94; 3; 4-2015; 203-211
dc.identifier.issn
0006-2952
dc.identifier.uri
http://hdl.handle.net/11336/13665
dc.description.abstract
Changes in expression of liver ABC transporters have been described during acute APAP intoxication. However, the effect of APAP on brain ABC transporters is poorly understood. The aim of this study was to evaluate the effect of APAP on brain ABC transporters expression and the role of the oxidative stress sensor Nrf2. Male C57BL/6J mice were administered APAP (400 mg/kg) for analysis of brain mRNA and protein expression of Mrp1-6, Bcrp and P-gp. The results show induction of P-gp, Mrp2 and Mrp4 proteins, with no changes in Bcrp, Mrp1 or Mrp5-6. The protein values were accompanied by corresponding changes in mRNA levels. Additionally, brain Nrf2 nuclear translocation and expression of two Nrf2 target genes, NAD(P)H:quinone oxidoreductase 1 (Nqo1) and Hemoxygenase 1 (Ho-1), was evaluated at 6, 12 and 24 h after APAP treatment. Nrf2 nuclear content increased by 58% at 12 h after APAP along with significant increments in mRNA and protein expression of Nqo1 and Ho-1. Furthermore, APAP treated Nrf2 knockout mice did not increase mRNA or protein expression of Mrp2 and Mrp4 as observed in wildtypes. In contrast, P-gp induction by APAP was observed in both genotypes. In conclusion, acute APAP intoxication induces protein expression of brain P-gp, Mrp2 and Mrp4. This study also suggests that brain changes in Mrp2 and Mrp4 expression may be due to in situ Nrf2 activation by APAP, while P-gp induction is independent of Nrf2 function. The functional consequences of these changes in brain ABC transporters by APAP deserve further attention.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier Inc
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject
Acetaminophen
dc.subject
Abc Transporters
dc.subject
Brain
dc.subject
Nrf2
dc.subject.classification
Otras Ciencias Biológicas
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Role of nuclear factor-erythroid 2-related factor 2 (Nrf2) in the transcriptional regulation of brain ABC transporters during acute acetaminophen (APAP) intoxication in mice
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-03-07T15:20:14Z
dc.journal.volume
94
dc.journal.number
3
dc.journal.pagination
203-211
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: Ghanem, Carolina Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas (i); Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
dc.description.fil
Fil: Rudraiah, Swetha. University Of Connecticut; Estados Unidos
dc.description.fil
Fil: Bataille, Amy M.. University Of Connecticut; Estados Unidos
dc.description.fil
Fil: Vigo, María B.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Farmacológicas (i); Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina
dc.description.fil
Fil: Goedken, Michael J.. Rutgers University. Office of Translational Science; Estados Unidos
dc.description.fil
Fil: Manautou, José E.. University Of Connecticut; Estados Unidos
dc.journal.title
Biochemical Pharmacology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0006295215000829
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.bcp.2015.01.013


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