Please use this identifier to cite or link to this item:
http://hdl.handle.net/10553/49178
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Martin, Daniel | en_US |
dc.contributor.author | Rojo, Ana I. | en_US |
dc.contributor.author | Salinas, Marta | en_US |
dc.contributor.author | Diaz, Raquel | en_US |
dc.contributor.author | Gallardo, German | en_US |
dc.contributor.author | Alam, Jawed | en_US |
dc.contributor.author | Ruiz De Galarreta Hernandez,C. Manuel | en_US |
dc.contributor.author | Cuadrado, Antonio | en_US |
dc.date.accessioned | 2018-11-24T04:54:33Z | - |
dc.date.available | 2018-11-24T04:54:33Z | - |
dc.date.issued | 2004 | en_US |
dc.identifier.issn | 0021-9258 | en_US |
dc.identifier.uri | http://hdl.handle.net/10553/49178 | - |
dc.description.abstract | The 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. | en_US |
dc.language | eng | en_US |
dc.relation.ispartof | Journal of Biological Chemistry | en_US |
dc.source | Journal of Biological Chemistry[ISSN 0021-9258],v. 279, p. 8919-8929 | en_US |
dc.subject | 32 Ciencias médicas | en_US |
dc.subject | 2302 Bioquímica | en_US |
dc.subject.other | Protein-Kinase-C | en_US |
dc.subject.other | Renal Epithelial-Cells | en_US |
dc.subject.other | Oxidative Stress | en_US |
dc.subject.other | Gene-Expression | en_US |
dc.subject.other | Nf-E2-Related Factor-2 | en_US |
dc.subject.other | Endothelial-Cells | en_US |
dc.subject.other | Primary Cultures | en_US |
dc.subject.other | Rat Hepatocytes | en_US |
dc.subject.other | Sodium Arsenite | en_US |
dc.subject.other | Induction | en_US |
dc.title | Regulation of Heme Oxygenase-1 Expression through the Phosphatidylinositol 3-Kinase/Akt Pathway and the Nrf2 Transcription Factor in Response to the Antioxidant Phytochemical Carnosol | en_US |
dc.type | info:eu-repo/semantics/Article | en_US |
dc.type | Article | en_US |
dc.identifier.doi | 10.1074/jbc.M309660200 | en_US |
dc.identifier.scopus | 1542335553 | - |
dc.identifier.isi | 000189265900050 | - |
dc.contributor.authorscopusid | 56484788100 | - |
dc.contributor.authorscopusid | 7005764407 | - |
dc.contributor.authorscopusid | 7006754360 | - |
dc.contributor.authorscopusid | 7201925856 | - |
dc.contributor.authorscopusid | 57197332997 | - |
dc.contributor.authorscopusid | 6603046608 | - |
dc.contributor.authorscopusid | 7102958617 | - |
dc.contributor.authorscopusid | 7003806034 | - |
dc.contributor.authorscopusid | 7005588564 | - |
dc.description.lastpage | 8929 | en_US |
dc.description.firstpage | 8919 | en_US |
dc.relation.volume | 279 | en_US |
dc.investigacion | Ciencias de la Salud | en_US |
dc.type2 | Artículo | en_US |
dc.contributor.daisngid | 1575213 | - |
dc.contributor.daisngid | 330184 | - |
dc.contributor.daisngid | 9538013 | - |
dc.contributor.daisngid | 11977739 | - |
dc.contributor.daisngid | 7801524 | - |
dc.contributor.daisngid | 102954 | - |
dc.contributor.daisngid | 1664323 | - |
dc.contributor.daisngid | 29362754 | - |
dc.description.numberofpages | 11 | en_US |
dc.utils.revision | Sí | en_US |
dc.contributor.wosstandard | WOS:Martin, D | - |
dc.contributor.wosstandard | WOS:Rojo, AI | - |
dc.contributor.wosstandard | WOS:Salinas, M | - |
dc.contributor.wosstandard | WOS:Diaz, R | - |
dc.contributor.wosstandard | WOS:Gallardo, G | - |
dc.contributor.wosstandard | WOS:Alam, J | - |
dc.contributor.wosstandard | WOS:de Galarreta, CMR | - |
dc.contributor.wosstandard | WOS:Cuadrado, A | - |
dc.date.coverdate | Marzo 2004 | en_US |
dc.identifier.ulpgc | Sí | en_US |
dc.contributor.buulpgc | BU-MED | en_US |
dc.description.jcr | 6,355 | - |
dc.description.jcrq | Q1 | - |
dc.description.scie | SCIE | - |
item.fulltext | Sin texto completo | - |
item.grantfulltext | none | - |
crisitem.author.dept | GIR Didáctica, Aprendizaje y Motivación en Contextos Específicos | - |
crisitem.author.dept | Departamento de Didácticas Específicas | - |
crisitem.author.dept | GIR Biomaterials and Biomechanics Research Group | - |
crisitem.author.dept | Departamento de Ingeniería Mecánica | - |
crisitem.author.orcid | 0000-0002-1516-1750 | - |
crisitem.author.orcid | 0000-0002-8599-781X | - |
crisitem.author.parentorg | Departamento de Educación | - |
crisitem.author.parentorg | Departamento de Ingeniería Mecánica | - |
crisitem.author.fullName | Gallardo Campos, Germán | - |
crisitem.author.fullName | Ruiz De Galarreta Hernandez,C. Manuel | - |
crisitem.author.fullName | Cuadrado Hernández, Alberto Javier | - |
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