Identificador persistente para citar o vincular este elemento: http://hdl.handle.net/10553/54421
Título: Selective activation of liver X receptors by acanthoic acid-related diterpenes
Autores/as: Traves, Paqui G.
Hortelano, Sonsoles
Zeini, Miriam
Chao, Ta Hsiang
Lam, Thanh
Neuteboom, Saskia T.
Theodorakis, Emmanuel A.
Palladino, Michael A.
Castrillo, Antonio 
Bosca, Lisardo
Palabras clave: Lxr-Alpha
Nuclear Receptors
Lipid-Metabolism
Oxysterol Receptors
Rxr Heterodimers, et al.
Fecha de publicación: 2007
Editor/a: 0026-895X
Publicación seriada: Molecular Pharmacology 
Resumen: Terpenoids 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.
URI: http://hdl.handle.net/10553/54421
ISSN: 0026-895X
DOI: 10.1124/mol.106.031906
Fuente: Molecular Pharmacology[ISSN 0026-895X],v. 71, p. 1545-1553
Colección:Artículos
Vista completa

Google ScholarTM

Verifica

Altmetric


Comparte



Exporta metadatos



Los elementos en ULPGC accedaCRIS están protegidos por derechos de autor con todos los derechos reservados, a menos que se indique lo contrario.