Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/54421
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dc.contributor.authorTraves, Paqui G.
dc.contributor.authorHortelano, Sonsoles
dc.contributor.authorZeini, Miriam
dc.contributor.authorChao, Ta Hsiang
dc.contributor.authorLam, Thanh
dc.contributor.authorNeuteboom, Saskia T.
dc.contributor.authorTheodorakis, Emmanuel A.
dc.contributor.authorPalladino, Michael A.
dc.contributor.authorCastrillo, Antonio
dc.contributor.authorBosca, Lisardo
dc.date.accessioned2019-02-18T10:42:43Z-
dc.date.available2019-02-18T10:42:43Z-
dc.date.issued2007
dc.identifier.issn0026-895X
dc.identifier.urihttp://hdl.handle.net/10553/54421-
dc.description.abstractTerpenoids constitute a large family of natural steroids that are widely distributed in plants and insects. We investigated the effects of a series of diterpenes structurally related to acanthoic acid in macrophage functions. We found that diterpenes with different substitutions at the C4 position in ring A are potent activators of liver X receptors (LXR alpha and LXR beta) in both macrophage cell lines from human and mouse origin and primary murine macrophages. Activation of LXR by these diterpenes was evaluated in transient transfection assays and gene expression analysis of known LXR-target genes, including the cholesterol transporters ABCA1 and ABCG1, the sterol regulatory element-binding protein 1c, and the apoptosis inhibitor of macrophages (Sp alpha). Moreover, active diterpenes greatly stimulated cholesterol efflux from macrophages. It is interesting that these diterpenes antagonize inflammatory gene expression mainly through LXR-dependent mechanisms, indicating that these compounds can activate both LXR activation and repression functions. Stimulation of macrophages with acanthoic acid diterpenes induced LXR-target gene expression and cholesterol efflux to similar levels observed with synthetic agonists 3-[3-[N-(2-chloro-3-trifluoromethylbenzyl)-(2,2-diphenylethyl)amino] propyloxy] phenylacetic acid hydrochloride (GW3965) and N-(2,2,2-trifluoroethyl)-N-[4-[2,2,2-trifluoro-1-hydroxy-1(trifluoromethyl)-ethyl] phenyl]-benzenesulfonamide [T1317 (T0901317)]. These effects observed in gene expression were deficient in macrophages lacking both LXR isoforms (LXR alpha, beta(-/-)). These results show the ability of certain acanthoic acid diterpenes to activate efficiently both LXRs and suggest that these compounds can exert beneficial effects from a cardiovascular standpoint through LXR-dependent mechanisms.
dc.publisher0026-895X
dc.relation.ispartofMolecular Pharmacology
dc.sourceMolecular Pharmacology[ISSN 0026-895X],v. 71, p. 1545-1553
dc.subject.otherLxr-Alpha
dc.subject.otherNuclear Receptors
dc.subject.otherLipid-Metabolism
dc.subject.otherOxysterol Receptors
dc.subject.otherRxr Heterodimers
dc.subject.otherGene-Expression
dc.subject.otherPpar-Gamma
dc.subject.otherCholesterol
dc.subject.otherAtherosclerosis
dc.subject.otherInflammation
dc.titleSelective activation of liver X receptors by acanthoic acid-related diterpenes
dc.typeinfo:eu-repo/semantics/Article
dc.typeArticle
dc.identifier.doi10.1124/mol.106.031906
dc.identifier.scopus34347332461
dc.identifier.isi000246979500011
dc.contributor.authorscopusid9236587900
dc.contributor.authorscopusid6701812151
dc.contributor.authorscopusid6602421859
dc.contributor.authorscopusid7202892359
dc.contributor.authorscopusid8754458300
dc.contributor.authorscopusid6602091298
dc.contributor.authorscopusid7005972947
dc.contributor.authorscopusid35461882200
dc.contributor.authorscopusid55445301000
dc.contributor.authorscopusid35514045400
dc.description.lastpage1553
dc.description.firstpage1545
dc.relation.volume71
dc.type2Artículo
dc.contributor.daisngid998475
dc.contributor.daisngid553977
dc.contributor.daisngid2442782
dc.contributor.daisngid2864881
dc.contributor.daisngid3602144
dc.contributor.daisngid642715
dc.contributor.daisngid201200
dc.contributor.daisngid31444756
dc.contributor.daisngid225640
dc.contributor.daisngid73057
dc.contributor.wosstandardWOS:Traves, PG
dc.contributor.wosstandardWOS:Hortelano, S
dc.contributor.wosstandardWOS:Zeini, M
dc.contributor.wosstandardWOS:Chao, TH
dc.contributor.wosstandardWOS:Lam, T
dc.contributor.wosstandardWOS:Neuteboom, ST
dc.contributor.wosstandardWOS:Theodorakis, EA
dc.contributor.wosstandardWOS:Palladino, MA
dc.contributor.wosstandardWOS:Castrillo, A
dc.contributor.wosstandardWOS:Bosca, L
dc.date.coverdateJunio 2007
dc.identifier.ulpgces
dc.description.jcr4,088
dc.description.jcrqQ1
dc.description.scieSCIE
item.fulltextSin texto completo-
item.grantfulltextnone-
crisitem.author.deptGIR IUIBS: Farmacología Molecular y Traslacional-
crisitem.author.deptIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.orcid0000-0002-2057-2159-
crisitem.author.parentorgIU de Investigaciones Biomédicas y Sanitarias-
crisitem.author.fullNameCastrillo Viguera, Antonio Jesús-
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