dc.contributor.author
Feldmann, Radmila
dc.contributor.author
Geikowski, Anne
dc.contributor.author
Weidner, Christopher
dc.contributor.author
Witzke, Annabell
dc.contributor.author
Kodelja, Vitam
dc.contributor.author
Schwarz, Thomas
dc.contributor.author
Gabriel, Mario
dc.contributor.author
Erker, Thomas
dc.contributor.author
Sauer, Sascha
dc.date.accessioned
2018-06-08T03:42:21Z
dc.date.available
2015-10-06T13:26:07.579Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/15764
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-19951
dc.description.abstract
Objective The liver X receptor α (LXRα) is a ligand-dependent nuclear receptor
and the major regulator of reverse cholesterol transport in macrophages. This
makes it an interesting target for mechanistic study and treatment of
atherosclerosis. Methods and Results We optimized a promising stilbenoid
structure (STX4) in order to reach nanomolar effective concentrations in LXRα
reporter-gene assays. STX4 displayed the unique property to activate LXRα
effectively but not its subtype LXRβ. The potential of STX4 to increase
transcriptional activity as an LXRα ligand was tested with gene expression
analyses in THP1-derived human macrophages and oxLDL-loaded human foam cells.
Only in foam cells but not in macrophage cells STX4 treatment showed athero-
protective effects with similar potency as the synthetic LXR ligand T0901317
(T09). Surprisingly, combinatorial treatment with STX4 and T09 resulted in an
additive effect on reporter-gene activation and target gene expression. In
physiological tests the cellular content of total and esterified cholesterol
was significantly reduced by STX4 without the undesirable increase in
triglyceride levels as observed for T09. Conclusions STX4 is a new LXRα-ligand
to study transcriptional regulation of anti-atherogenic processes in cell or
ex vivo models, and provides a promising lead structure for pharmaceutical
development.
en
dc.rights.uri
http://creativecommons.org/licenses/by/2.0/de/
dc.subject.ddc
500 Naturwissenschaften und Mathematik::570 Biowissenschaften; Biologie
dc.title
Foam Cell Specific LXRα Ligand
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
PLoS ONE. - 8 (2013), 2, Artikel Nr. e57311
dcterms.bibliographicCitation.doi
10.1371/journal.pone.0057311
dcterms.bibliographicCitation.url
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0057311
refubium.affiliation
Biologie, Chemie, Pharmazie
de
refubium.mycore.fudocsId
FUDOCS_document_000000023238
refubium.note.author
Der Artikel wurde in einer Open-Access-Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000005498
dcterms.accessRights.openaire
open access