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1 LXRalpha deletion in mice increases the availability of
2 LXRalpha forms a heterodimer with RXRalpha, another memb
3 LXRalpha may serve as a glucose sensor and, along with C
4 LXRalpha occupancy at the CCR7 promoter is enhanced and
5 LXRalpha was shown to bind specifically to this LXRE and
6 LXRalpha(-/-), LXRbeta(-/-), and LXRalpha/beta(-/-) mice
7 LXRalpha, LXRbeta, ATP-binding cassette transporter A1 (
8 s accumulate oxidized lipids, which activate LXRalpha and LXRbeta, resulting in the induction of ABCA
9 that the interaction between cAMP-activated LXRalpha and the CNRE enhancer element is responsible fo
10 KI) mice in which a constitutively activated LXRalpha (VP-LXRalpha) was inserted into the mouse LXRal
12 he nuclear receptors liver X receptor alpha (LXRalpha) (NR1H3) and LXRbeta (NR1H2) are important regu
13 Dysregulation of liver X receptor alpha (LXRalpha) activity has been linked to cardiovascular and
14 ar hormone receptors liver X receptor alpha (LXRalpha) and LXRbeta function as physiological receptor
15 2 interacts with the liver X receptor alpha (LXRalpha) and the estrogen receptor alpha (ERalpha).
16 e unexpected role of liver X receptor alpha (LXRalpha) as a direct transcriptional inhibitor of beta-
19 for oxysterols, the liver X receptor alpha (LXRalpha), regulates cholesterol biosynthesis by directl
23 ight be mediated via liver-X receptor alpha (LXRalpha)/ATP-binding cassette transporter A1 (ABCA1) pa
24 nic nuclear receptor liver X receptor alpha (LXRalpha; Nr1h3) and its downstream targets, including A
25 rted previously that liver X receptor-alpha (LXRalpha) can mediate a novel cAMP-dependent increase in
27 ear hormone receptor liver X receptor-alpha (LXRalpha) is a major transcriptional regulator of the ex
28 activation by Vpr of liver X receptor-alpha (LXRalpha) with increased expression of its lipogenic tar
29 ed that ATF6 induces liver X receptor-alpha (LXRalpha), an Mertk-inducing transcription factor, and t
31 e receptor known as liver X receptor alpha, (LXRalpha [NR1H3]), which is the physiological receptor f
33 , an FXR ligand, and taurohyocholic acid, an LXRalpha ligand, were significantly increased by IT (P <
34 rect LXRalpha target genes, we identified an LXRalpha occupancy site within the second intron of the
36 recruitment of the corepressor RIP140 to an LXRalpha binding site that overlaps with the PPARgamma/P
37 ng polyunsaturated fatty acids, linked to an LXRalpha-dependent increase in expression of enzymes med
40 d that Sp1 interacted with both SREBP-1c and LXRalpha proteins and that insulin promoted these intera
44 ting structures of the LXRbeta homodimer and LXRalpha:RXR (retinoid X receptor) heterodimers explains
45 ogenic genes in the absence of Lxralpha, and LXRalpha was unable to induce the lipogenic genes in the
46 played good binding affinity for LXRbeta and LXRalpha and were potent activators in LBD transactivati
51 he profiles from the livers of wild-type and LXRalpha/LXRbeta-null mice after exposure to the LXR ago
52 E(-/-) mice was further enhanced in ApoE(-/-)LXRalpha(-/-) double knockout mice and was accompanied b
54 dings identify a macrophage CaMKIIgamma/ATF6/LXRalpha/MerTK pathway as a key factor in the developmen
58 on nuclear liver X receptors alpha and beta (LXRalpha,beta), peroxisome proliferator-activated recept
59 richment of liver X receptor alpha and beta (LXRalpha/beta) in the nodose ganglia of the vagus nerve.
60 ligands for liver X receptors alpha and beta(LXRalpha and LXRbeta), which are important in regulating
67 Macrophages derived from mice lacking both LXRalpha and LXRbeta failed to up-regulate the expressio
68 es and liver is lost in animals lacking both LXRalpha and LXRbeta, confirming the critical role of th
70 t of a number of cofactor peptides onto both LXRalpha and LXRbeta and showed an EC(50) of approximate
71 nd by immunohistochemical staining that both LXRalpha and LXRbeta are expressed in the cell nuclei of
72 binding assay confirmed that 4 binds to both LXRalpha and LXRbeta directly and recruits coactivator p
74 city to convert cholesterol to bile acids by LXRalpha-mediated stimulation of CYP7A1 transcription, w
75 ha and suggest that FAS, which is induced by LXRalpha, may generate regulatory lipids that cause feed
76 herefore, gene transcription is regulated by LXRalpha S198 phosphorylation, including that of antiath
77 ile acids in the liver, is also regulated by LXRalpha suggests that this class of nuclear receptor co
80 gene promoter by RORalpha was suppressed by LXRalpha (NR1H3), whereas RORalpha inhibited both the co
81 MP promotes transcription through c-myc/CNRE:LXRalpha interaction in LXRalpha transiently transfected
84 ary function of this LXR isoform, we created LXRalpha knock-in (LXR-KI) mice in which a constitutivel
85 RXR repression was associated with decreased LXRalpha and PPARalpha mRNA levels and reduced RXR x RXR
89 regression, mRNA levels of the gene encoding LXRalpha are increased in plaque CD68+ cells, suggestive
90 athway comprising miR-155 and its epigenetic LXRalpha target that when deregulated enables pathogenic
92 = 53 nM), it had little binding affinity for LXRalpha (IC(50) > 1.0 microM) and did not recruit any c
93 ctionality of these CNREs by competition for LXRalpha binding via electrophoretic mobility shift assa
96 beta-/- mice confirm an equivalent role for LXRalpha and LXRbeta in the regulation of ABCA1 and SREB
97 a region that contains two binding sites for LXRalpha and is known to be required for insulin inducti
99 dose-response studies with macrophages from LXRalpha-/- and beta-/- mice confirm an equivalent role
100 uclear receptors farnesoid X receptor (FXR), LXRalpha, liver receptor homolog (LRH-1), hepatocyte nuc
101 cally relevant human nuclear receptors (FXR, LXRalpha/beta, CAR, PXR, VDR and PPARalpha/gamma/delta)
102 BPbeta(-/-) mice, the anti-inflammatory gene LXRalpha and its targets SCD1 and DGAT2 were strikingly
104 thesis/flux associated with elevated hepatic LXRalpha and PPARalpha mRNA levels as well as impaired h
106 herogenic activity in the absence of hepatic LXRalpha, indicating that the ability of agonists to red
109 discovered that the mouse homologue of human LXRalpha binds to the CNRE and demonstrated that it bind
111 the steroid receptor coactivator-1 to human LXRalpha and LXRbeta with EC(50)s of 40 nM, profiles as
112 NA, and protein levels, directly implicating LXRalpha/beta in the transcriptional control of myelin g
114 expression of the LXR target gene, ABCA1, in LXRalpha/beta-deficient mouse fibroblasts, but was fully
115 We studied pan-LXRalpha/beta agonists in LXRalpha knockout mice to assess the contribution of LXR
116 d treated with the LXR agonist GW3965 and in LXRalpha(-/-), LXRbeta(-/-), and LXRalpha/beta(-/-) mice
117 acid synthesis genes was not derepressed in LXRalpha-deficient hosts, indicating that the antiviral
118 n through c-myc/CNRE:LXRalpha interaction in LXRalpha transiently transfected cells and increases c-m
119 vident at a single conserved lysine (K432 in LXRalpha and K433 in LXRbeta) adjacent to the ligand-reg
120 used a partial reduction in ear thickness in LXRalpha-/- animals, however (approximately 50% of that
121 activated poised enhancers to rapidly induce LXRalpha and other Kupffer cell lineage-determining fact
122 than 20:4,n6 at inhibiting oxysterol-induced LXRalpha activity in HEK293-E cells, but had no effect o
124 ate that the liver X receptor alpha isoform (LXRalpha) restricts gammaherpesvirus reactivation in an
125 Previous work has shown that mice lacking LXRalpha accumulate cholesterol in the liver but not in
128 The nuclear receptors liver X receptor (LXR) LXRalpha and LXRbeta are differentially expressed ligand
129 ralpha and Srebp1c promoters, increased LXRE-LXRalpha binding, and broadly altered hepatic expression
130 ing the role of the liver X receptors (LXRs) LXRalpha and LXRbeta in carbohydrate sensing by the live
131 trate here that the liver X receptors (LXRs) LXRalpha and LXRbeta inhibit basal and cytokine-inducibl
132 ic role: it is required for NCoA6 to mediate LXRalpha-regulated lipogenesis and cholesterol/bile acid
135 RAW264.7 cells expressing nonphosphorylated LXRalpha (RAW-LXRalpha S198A) compared to RAW264.7 cells
136 R7 by ligands that promote nonphosphorylated LXRalpha S198, and this was lost in LXR-deficient BMDMs.
137 n free access to water, LXRbeta(-/-) but not LXRalpha(-/-) mice exhibited polyuria (abnormal daily ex
139 ion and mass spectrometry to analyze nuclear LXRalpha complexes and identified poly(ADP-ribose) polym
142 To determine whether this novel action of LXRalpha has global implications on gene regulation, we
143 ession analysis indicated that activation of LXRalpha affected lipid metabolic networks and increased
154 tic LXR agonists, liver-specific deletion of LXRalpha eliminated the detrimental effect of increased
156 genic background, liver-specific deletion of LXRalpha increased atherosclerosis, uncovering an import
158 ed specifically for the lipogenic effects of LXRalpha and that manipulation of the insulin signaling
161 ogenetic genes, along with the expression of LXRalpha and its target genes sterol regulatory element-
162 cifically, in mice, transgenic expression of LXRalpha in macrophages significantly ameliorated hyperl
166 e that express a constitutive active form of LXRalpha only in the intestinal epithelium, under the co
167 nhibition by dominant negative (DN) forms of LXRalpha and LXRbeta reduced calcium content in CVCs.
169 show that expression of two target genes of LXRalpha, the ATP-binding cassette (ABC) transporters Ab
170 creases atherosclerosis through induction of LXRalpha and suggest that FAS, which is induced by LXRal
175 of ABCA1 and SREBP-1c genes in the liver of LXRalpha null animals than in treated wild-type controls
176 in a phenotype more specific to the loss of LXRalpha, including hypercorticosteronemia, cholesterol
185 of this study was to investigate the role of LXRalpha on the regulation of rat, human and hamster CYP
186 ese studies further distinguish the roles of LXRalpha and beta and support a growing body of evidence
187 ges in gene expression and identify a set of LXRalpha/cAMP-regulated genes that may have important bi
194 unsaturated fatty acids had little effect on LXRalpha activity in primary hepatocytes or FTO-2B.
197 mice that also lacked TLR2, TLR4, MyD88, or LXRalpha intranasally with C. pneumoniae followed by fee
198 age) cells but had no effect on PPARalpha or LXRalpha receptor activity in HEK293-L (late passage) ce
199 s from 293T cells transfected with TRbeta or LXRalpha expression plasmids show that TR, together with
202 MP stimulation of murine MSCs overexpressing LXRalpha led to their differentiation into JG-like cells
205 a clinically viable, highly brain-penetrant LXRalpha-partial/LXRbeta-full agonist selectively kills
207 ges were accompanied by increased PPARalpha, LXRalpha, ABCA1 and ABCG1 expressions in the liver.
209 e effect of NAMPT knockdown on the PPARalpha-LXRalpha pathway of cholesterol metabolism with MK886 (a
210 transcription factors (SREBP-1c, PPARgamma, LXRalpha) was increased, whereas that of a lipolytic nuc
213 s expressing nonphosphorylated LXRalpha (RAW-LXRalpha S198A) compared to RAW264.7 cells expressing wi
215 ted RAW-LXRalpha S198A cells compared to RAW-LXRalpha WT cells revealed induction of cell migratory a
216 Expression profiling of ligand-treated RAW-LXRalpha S198A cells compared to RAW-LXRalpha WT cells r
218 as developed for the orphan nuclear receptor LXRalpha that measures the ligand-dependent recruitment
219 ression and activity of the nuclear receptor LXRalpha, leading to increased hepatic cholesterol and a
221 aneous coactivation of the liver X receptor, LXRalpha, a nuclear hormone receptor with known roles in
223 demonstrate here that the nuclear receptors LXRalpha and LXRbeta and their oxysterol ligands are key
226 report that SUMOylation of nuclear receptors LXRalpha and LXRbeta plays a critical role in the transr
228 ily transcription factors Liver X Receptors (LXRalpha and -beta) are expressed in cartilage, with LXR
231 udies have identified the liver X receptors (LXRalpha and LXRbeta) as important regulators of cholest
232 , we show the role of the liver X receptors (LXRalpha and LXRbeta) in preventing accumulation of free
234 g" nuclear receptors, the liver X receptors (LXRalpha/LXRbeta), protects against atherosclerosis by t
235 have discovered that the Liver-X-Receptors (LXRalpha and LXRbeta), nuclear receptors known to regula
238 or Nuclear Receptors (NR) PPARalpha/RXRalpha/LXRalpha, enhance EGFR expression, mediated by the promo
239 s, 21, 27, and 28 were found to be selective LXRalpha agonists, whereas 20, 22, and 25 showed good se
241 tivity approximately 2.2-fold and suppressed LXRalpha activity by 80% (ED50 approximately 25-50 micro
242 ugh a TLR/MyD88-dependent mechanism and that LXRalpha appears to reciprocally modulate and reduce the
245 lectromobility shift assays demonstrate that LXRalpha and retinoid X receptor alpha bind to the two L
248 n parallel experiments, we demonstrated that LXRalpha can also bind to the homologous CNRE in the c-m
249 8 (MHV68) reporter virus, we discovered that LXRalpha expression dictates the cellular tropism of MHV
250 striking contrast, we demonstrate here that LXRalpha(-/-)apoE(-/-) mice exhibit extreme cholesterol
251 In this study we test the hypothesis that LXRalpha plays an important role not only in renin expre
253 ct a recent Nature report that proposed that LXRalpha/beta sense glucose independent of metabolic flu
254 issue of the JCI, Cummins et al. report that LXRalpha is involved in similar regulation in the adrena
256 n coupled with deep sequencing revealed that LXRalpha and LXRbeta occupy both overlapping and exclusi
265 An inverse correlation between c-FOS and the LXRalpha pathway was also observed in human HCC cell lin
266 ith an LXRalpha agonist, lipogenesis and the LXRalpha target gene expression were significantly reduc
268 increased in RAW 264.7 cells expressing the LXRalpha S198A phosphorylation-deficient mutant compared
271 eta,25-diol 3-sulfate (25HC3S), inhibits the LXRalpha signaling and reduces lipogenesis by decreasing
272 tic LXR ligands induce the expression of the LXRalpha gene in primary human macrophages and different
274 h hLXRalpha or a chimera containing only the LXRalpha ligand binding domain, indicate that a wide arr
275 Our data implied that HLP up-regulated the LXRalpha/ABCA1 pathway, which in turn led to stimulation
277 n immunoprecipitation assays showed that the LXRalpha-C/EBPbeta complex binds to the SREBP-1c promote
278 st cells use metabolic signaling through the LXRalpha nuclear receptor to defend against Listeria mon
281 7 binds to LXRbeta with high affinity and to LXRalpha to a lesser extent, and induces the expression
284 these data suggest that reduced ROS triggers LXRalpha activation and macrophage reverse cholesterol t
285 tal of 69 compounds were found to upregulate LXRalpha and certain LXR regulated genes from 1308 compo
286 The results of this study, which utilized LXRalpha/beta double-KO mice, strongly contradict a rece
287 ose lipogenic diet, G0S2 is up-regulated via LXRalpha and required for the increased TG accumulation
288 hich a constitutively activated LXRalpha (VP-LXRalpha) was inserted into the mouse LXRalpha locus.
289 enovirus-mediated LXR overexpression by VP16-LXRalpha and VP16-LXRbeta accelerated mineralization of
293 S) and on the regulation of aquaporins while LXRalpha has its most marked effects on cholesterol home
295 t/FAS-deficient bone marrow as compared with LXRalpha-replete/FAS-deficient marrow, consistent with a
298 ese hamster ovary cells, cotransfection with LXRalpha stimulated reporter activity by less than 2-fol
300 e when apoE null mice were transplanted with LXRalpha-deficient/FAS-deficient bone marrow as compared