Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/49178
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dc.contributor.authorMartin, Daniel
dc.contributor.authorRojo, Ana I.
dc.contributor.authorSalinas, Marta
dc.contributor.authorDiaz, Raquel
dc.contributor.authorGallardo, German
dc.contributor.authorAlam, Jawed
dc.contributor.authorRuiz De Galarreta, Carlos M.
dc.contributor.authorCuadrado, Antonio
dc.date.accessioned2018-11-24T04:54:33Z-
dc.date.available2018-11-24T04:54:33Z-
dc.date.issued2004
dc.identifier.issn0021-9258
dc.identifier.urihttp://hdl.handle.net/10553/49178-
dc.description.abstractThe phosphatidylinositol 3-kinase (PI3K)/Akt pathway elicits a survival signal against multiple apoptotic insults. In addition, phase II enzymes such as heme oxygenase-1 (HO-1) protect cells against diverse toxins and oxidative stress. In this work, we describe a link between these defense systems at the level of transcriptional regulation of the antioxidant enzyme HO-1. The herb-derived phenol carnosol induced HO-1 expression at both mRNA and protein levels. Luciferase reporter assays indicated that carnosol targeted the mouse ho1 promoter at two enhancer regions comprising the antioxidant response elements (AREs). Moreover, carnosol increased the nuclear levels of Nrf2, a transcription factor governing AREs. Electrophoretic mobility shift assays and luciferase reporter assays with a dominant-negative Nrf2 mutant indicated that carnosol increased the binding of Nrf2 to ARE and induced Nrf2-dependent activation of the ho1 promoter. While investigating the signaling pathways responsible for HO-1 induction, we observed that carnosol activated the ERK, p38, and JNK pathways as well as the survival pathway driven by PI3K. Inhibition of PI3K reduced the increase in Nrf2 protein levels and activation of the ho1 promoter. Expression of active PI3K-CAAX ( where A is aliphatic amino acid) was sufficient to activate AREs. The use of dominant-negative mutants of protein kinase Czeta and Akt1, two kinases downstream from PI3K, demonstrated a requirement for active Akt1, but not protein kinase Czeta. Moreover, the long-term antioxidant effect of carnosol was partially blocked by PI3K or HO-1 inhibitors, further demonstrating that carnosol attenuates oxidative stress through a pathway that involves PI3K and HO-1.
dc.publisher0021-9258
dc.relation.ispartofJournal of Biological Chemistry
dc.sourceJournal of Biological Chemistry[ISSN 0021-9258],v. 279, p. 8919-8929
dc.subject.otherProtein-Kinase-C
dc.subject.otherRenal Epithelial-Cells
dc.subject.otherOxidative Stress
dc.subject.otherGene-Expression
dc.subject.otherNf-E2-Related Factor-2
dc.subject.otherEndothelial-Cells
dc.subject.otherPrimary Cultures
dc.subject.otherRat Hepatocytes
dc.subject.otherSodium Arsenite
dc.subject.otherInduction
dc.titleRegulation of Heme Oxygenase-1 Expression through the Phosphatidylinositol 3-Kinase/Akt Pathway and the Nrf2 Transcription Factor in Response to the Antioxidant Phytochemical Carnosol
dc.typeinfo:eu-repo/semantics/Articlees
dc.typeArticlees
dc.identifier.doi10.1074/jbc.M309660200
dc.identifier.scopus1542335553
dc.identifier.isi000189265900050
dc.contributor.authorscopusid56484788100
dc.contributor.authorscopusid7005764407
dc.contributor.authorscopusid7006754360
dc.contributor.authorscopusid7201925856
dc.contributor.authorscopusid57197332997
dc.contributor.authorscopusid6603046608
dc.contributor.authorscopusid7102958617
dc.contributor.authorscopusid7003806034
dc.contributor.authorscopusid7005588564
dc.description.lastpage8929
dc.description.firstpage8919
dc.relation.volume279
dc.type2Artículoes
dc.contributor.daisngid1575213
dc.contributor.daisngid330184
dc.contributor.daisngid9538013
dc.contributor.daisngid11977739
dc.contributor.daisngid7801524
dc.contributor.daisngid102954
dc.contributor.daisngid1664323
dc.contributor.daisngid29362754
dc.contributor.wosstandardWOS:Martin, D
dc.contributor.wosstandardWOS:Rojo, AI
dc.contributor.wosstandardWOS:Salinas, M
dc.contributor.wosstandardWOS:Diaz, R
dc.contributor.wosstandardWOS:Gallardo, G
dc.contributor.wosstandardWOS:Alam, J
dc.contributor.wosstandardWOS:de Galarreta, CMR
dc.contributor.wosstandardWOS:Cuadrado, A
dc.date.coverdateMarzo 2004
dc.identifier.ulpgces
dc.description.jcr6,355
dc.description.jcrqQ1
dc.description.scieSCIE
item.grantfulltextnone-
item.fulltextSin texto completo-
crisitem.author.deptGIR Medio Ambiente y Salud-
crisitem.author.deptIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.deptDepartamento de Didácticas Específicas-
crisitem.author.deptGIR Biomaterials and Biomechanics Research Group-
crisitem.author.deptDepartamento de Ingeniería Mecánica-
crisitem.author.orcid0000-0002-1516-1750-
crisitem.author.orcid0000-0002-8599-781X-
crisitem.author.parentorgIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.parentorgDepartamento de Ingeniería Mecánica-
crisitem.author.fullNameGallardo Campos, Germán-
crisitem.author.fullNameCuadrado Hernández, Alberto Javier-
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