ライフサイエンスコーパス: LXRalpha

1 LXRalpha and -beta are nuclear receptors that regulate t

2 LXRalpha deletion in mice increases the availability of

3 LXRalpha forms a heterodimer with RXRalpha, another memb

4 LXRalpha is a member of a nuclear receptor superfamily t

5 LXRalpha may serve as a glucose sensor and, along with C

6 LXRalpha occupancy at the CCR7 promoter is enhanced and

7 LXRalpha was shown to bind specifically to this LXRE and

8 LXRalpha(-/-), LXRbeta(-/-), and LXRalpha/beta(-/-) mice

9 LXRalpha, LXRbeta, ATP-binding cassette transporter A1 (

10 s accumulate oxidized lipids, which activate LXRalpha and LXRbeta, resulting in the induction of ABCA

11 that the interaction between cAMP-activated LXRalpha and the CNRE enhancer element is responsible fo

12 KI) mice in which a constitutively activated LXRalpha (VP-LXRalpha) was inserted into the mouse LXRal

13 Expression of activated LXRalpha blocks proliferation of human colorectal cancer

14 he nuclear receptors liver X receptor alpha (LXRalpha) (NR1H3) and LXRbeta (NR1H2) are important regu

15 Dysregulation of liver X receptor alpha (LXRalpha) activity has been linked to cardiovascular and

16 ar hormone receptors liver X receptor alpha (LXRalpha) and LXRbeta function as physiological receptor

17 2 interacts with the liver X receptor alpha (LXRalpha) and the estrogen receptor alpha (ERalpha).

18 e unexpected role of liver X receptor alpha (LXRalpha) as a direct transcriptional inhibitor of beta-

19 Knockdown of liver X receptor alpha (LXRalpha) inhibited ABC transporter expression in M(Hb)

20 ed innate immune and liver X receptor alpha (LXRalpha) signaling pathways.

21 for oxysterols, the liver X receptor alpha (LXRalpha), regulates cholesterol biosynthesis by directl

22 factor SREBP-1c and liver X receptor alpha (LXRalpha).

23 rs, most prominently liver x receptor alpha (LXRalpha).

24 on is upregulated by liver X receptor alpha (LXRalpha).

25 ight be mediated via liver-X receptor alpha (LXRalpha)/ATP-binding cassette transporter A1 (ABCA1) pa

26 nic nuclear receptor liver X receptor alpha (LXRalpha; Nr1h3) and its downstream targets, including A

27 rted previously that liver X receptor-alpha (LXRalpha) can mediate a novel cAMP-dependent increase in

28 ion by up-regulating liver X receptor-alpha (LXRalpha) in macrophages.

29 ear hormone receptor liver X receptor-alpha (LXRalpha) is a major transcriptional regulator of the ex

30 activation by Vpr of liver X receptor-alpha (LXRalpha) with increased expression of its lipogenic tar

31 ed that ATF6 induces liver X receptor-alpha (LXRalpha), an Mertk-inducing transcription factor, and t

32 ha (PPAR-alpha), and liver X receptor-alpha (LXRalpha).

33 e receptor known as liver X receptor alpha, (LXRalpha [NR1H3]), which is the physiological receptor f

34 We demonstrate here that although LXRalpha and LXRbeta are not required for adipocyte deve

35 , an FXR ligand, and taurohyocholic acid, an LXRalpha ligand, were significantly increased by IT (P <

36 rect LXRalpha target genes, we identified an LXRalpha occupancy site within the second intron of the

37 improves dietary cholesterol tolerance in an LXRalpha-independent manner.

38 recruitment of the corepressor RIP140 to an LXRalpha binding site that overlaps with the PPARgamma/P

39 ng polyunsaturated fatty acids, linked to an LXRalpha-dependent increase in expression of enzymes med

40 In contrast, when treated with an LXRalpha agonist, lipogenesis and the LXRalpha target ge

41 Interestingly, SR-A, SR-BII, LOX-1, and LXRalpha expression appeared to be slightly down-regulat

42 d that Sp1 interacted with both SREBP-1c and LXRalpha proteins and that insulin promoted these intera

43 tion factors involved are USF, SREBP-1c, and LXRalpha.

44 ABCG1 and SREBP-1c) or not induced (apoE and LXRalpha).

45 lesterol efflux and to increase ABCA1/G1 and LXRalpha expressions in RAW264.7 macrophages.

46 ting structures of the LXRbeta homodimer and LXRalpha:RXR (retinoid X receptor) heterodimers explains

47 ogenic genes in the absence of Lxralpha, and LXRalpha was unable to induce the lipogenic genes in the

48 played good binding affinity for LXRbeta and LXRalpha and were potent activators in LBD transactivati

49 LXRalpha(-/-), LXRbeta(-/-), and LXRalpha/beta(-/-) mice developed acellular capillaries

50 3965 and in LXRalpha(-/-), LXRbeta(-/-), and LXRalpha/beta(-/-) mice.

51 n important role in regulating PPARalpha and LXRalpha activity.

52 194,204, and T0901317 required PPARalpha and LXRalpha/LXRbeta for statistical significance.

53 he profiles from the livers of wild-type and LXRalpha/LXRbeta-null mice after exposure to the LXR ago

54 E(-/-) mice was further enhanced in ApoE(-/-)LXRalpha(-/-) double knockout mice and was accompanied b

55 LXRbeta, while it was virtually inactive at LXRalpha (EC50 = 14.51 muM).

56 dings identify a macrophage CaMKIIgamma/ATF6/LXRalpha/MerTK pathway as a key factor in the developmen

57 The liver X receptors alpha and beta (LXRalpha and LXRbeta) are important regulators of choles

58 receptors, liver X receptors alpha and beta (LXRalpha and LXRbeta).

59 on nuclear liver X receptors alpha and beta (LXRalpha,beta), peroxisome proliferator-activated recept

60 richment of liver X receptor alpha and beta (LXRalpha/beta) in the nodose ganglia of the vagus nerve.

61 ligands for liver X receptors alpha and beta(LXRalpha and LXRbeta), which are important in regulating

62 n factor C/EBPbeta, but a connection between LXRalpha and C/EBPbeta has not been made.

63 elements of the rat CYP7A1 were able to bind LXRalpha/RXRalpha and confer LXRalpha stimulation.

64 Both LXRalpha and LXRbeta transactivated the VEGF promoter in

65 Both LXRalpha and LXRbeta were present in VSMC, and their act

66 Both LXRalpha/RXRalpha and LXRbeta/RXRalpha transactivated th

67 APD) is a potent, selective agonist for both LXRalpha (NR1H3) and LXRbeta (NR1H2).

68 Plaques from both LXRalpha and LXRbeta-deficient Apoe-/- mice exhibited im

69 Macrophages derived from mice lacking both LXRalpha and LXRbeta failed to up-regulate the expressio

70 es and liver is lost in animals lacking both LXRalpha and LXRbeta, confirming the critical role of th

71 matitis, requiring the participation of both LXRalpha and LXRbeta.

72 t of a number of cofactor peptides onto both LXRalpha and LXRbeta and showed an EC(50) of approximate

73 nd by immunohistochemical staining that both LXRalpha and LXRbeta are expressed in the cell nuclei of

74 binding assay confirmed that 4 binds to both LXRalpha and LXRbeta directly and recruits coactivator p

75 In fact, PARP-1 interacted with both LXRalpha and LXRbeta.

76 city to convert cholesterol to bile acids by LXRalpha-mediated stimulation of CYP7A1 transcription, w

77 ha and suggest that FAS, which is induced by LXRalpha, may generate regulatory lipids that cause feed

78 herefore, gene transcription is regulated by LXRalpha S198 phosphorylation, including that of antiath

79 ile acids in the liver, is also regulated by LXRalpha suggests that this class of nuclear receptor co

80 sm through a process reportedly regulated by LXRalpha.

81 r SPalpha, a direct target for regulation by LXRalpha.

82 gene promoter by RORalpha was suppressed by LXRalpha (NR1H3), whereas RORalpha inhibited both the co

83 MP promotes transcription through c-myc/CNRE:LXRalpha interaction in LXRalpha transiently transfected

84 Under basal conditions, LXRalpha is phosphorylated at S198; phosphorylation is e

85 re able to bind LXRalpha/RXRalpha and confer LXRalpha stimulation.

86 ary function of this LXR isoform, we created LXRalpha knock-in (LXR-KI) mice in which a constitutivel

87 RXR repression was associated with decreased LXRalpha and PPARalpha mRNA levels and reduced RXR x RXR

88 rformed gene targeting to selectively delete LXRalpha in hepatocytes.

89 In a whole genome screen for direct LXRalpha target genes, we identified an LXRalpha occupan

90 nds in a cell-based reporter assay employing LXRalpha-GAL4 chimeric receptors.

91 regression, mRNA levels of the gene encoding LXRalpha are increased in plaque CD68+ cells, suggestive

92 athway comprising miR-155 and its epigenetic LXRalpha target that when deregulated enables pathogenic

93 s activated specifically in cells expressing LXRalpha S198A.

94 = 53 nM), it had little binding affinity for LXRalpha (IC(50) > 1.0 microM) and did not recruit any c

95 ctionality of these CNREs by competition for LXRalpha binding via electrophoretic mobility shift assa

96 Here, we describe a function for LXRalpha as a cAMP-responsive regulator of renin and c-m

97 iscover surprising, protective functions for LXRalpha in innate immunity.

98 mevalonic acid biosynthesis is required for LXRalpha activity.

99 However, insulin was not required for LXRalpha to modulate the phospholipid profile, or to sup

100 beta-/- mice confirm an equivalent role for LXRalpha and LXRbeta in the regulation of ABCA1 and SREB

101 -70 to -55 base pairs) as a binding site for LXRalpha/RXR or LXRbeta/RXR.

102 a region that contains two binding sites for LXRalpha and is known to be required for insulin inducti

103 uated in peritoneal macrophages derived from LXRalpha/beta null mice.

104 dose-response studies with macrophages from LXRalpha-/- and beta-/- mice confirm an equivalent role

105 uclear receptors farnesoid X receptor (FXR), LXRalpha, liver receptor homolog (LRH-1), hepatocyte nuc

106 cally relevant human nuclear receptors (FXR, LXRalpha/beta, CAR, PXR, VDR and PPARalpha/gamma/delta)

107 BPbeta(-/-) mice, the anti-inflammatory gene LXRalpha and its targets SCD1 and DGAT2 were strikingly

108 orable HDL increases, but circumvent hepatic LXRalpha-dominated lipogenesis.

109 thesis/flux associated with elevated hepatic LXRalpha and PPARalpha mRNA levels as well as impaired h

110 evealing the essential importance of hepatic LXRalpha for whole body cholesterol homeostasis.

111 herogenic activity in the absence of hepatic LXRalpha, indicating that the ability of agonists to red

112 However, LXRalpha did not bind to the corresponding sequences of

113 However, LXRalpha had much less effect on hamster and no signific

114 discovered that the mouse homologue of human LXRalpha binds to the CNRE and demonstrated that it bind

115 The human LXRalpha gene was isolated, and the transcription initia

116 the steroid receptor coactivator-1 to human LXRalpha and LXRbeta with EC(50)s of 40 nM, profiles as

117 NA, and protein levels, directly implicating LXRalpha/beta in the transcriptional control of myelin g

118 These results imply LXRalpha provides a safety valve to limit free cholester

119 expression of the LXR target gene, ABCA1, in LXRalpha/beta-deficient mouse fibroblasts, but was fully

120 We studied pan-LXRalpha/beta agonists in LXRalpha knockout mice to assess the contribution of LXR

121 d treated with the LXR agonist GW3965 and in LXRalpha(-/-), LXRbeta(-/-), and LXRalpha/beta(-/-) mice

122 n through c-myc/CNRE:LXRalpha interaction in LXRalpha transiently transfected cells and increases c-m

123 vident at a single conserved lysine (K432 in LXRalpha and K433 in LXRbeta) adjacent to the ligand-reg

124 used a partial reduction in ear thickness in LXRalpha-/- animals, however (approximately 50% of that

125 than 20:4,n6 at inhibiting oxysterol-induced LXRalpha activity in HEK293-E cells, but had no effect o

126 ding to LXR and antagonize oxysterol-induced LXRalpha activity.

127 Previous work has shown that mice lacking LXRalpha accumulate cholesterol in the liver but not in

128 In this study, we show mice lacking LXRalpha/beta in peripheral sensory neurons have increas

129 Last, LXRalpha luciferase reporter activity was increased in M

130 The nuclear receptors liver X receptor (LXR) LXRalpha and LXRbeta are differentially expressed ligand

131 ralpha and Srebp1c promoters, increased LXRE-LXRalpha binding, and broadly altered hepatic expression

132 ing the role of the liver X receptors (LXRs) LXRalpha and LXRbeta in carbohydrate sensing by the live

133 trate here that the liver X receptors (LXRs) LXRalpha and LXRbeta inhibit basal and cytokine-inducibl

134 ic role: it is required for NCoA6 to mediate LXRalpha-regulated lipogenesis and cholesterol/bile acid

135 ha (VP-LXRalpha) was inserted into the mouse LXRalpha locus.

136 ting it to be one of the most potent natural LXRalpha ligands known to date.

137 RAW264.7 cells expressing nonphosphorylated LXRalpha (RAW-LXRalpha S198A) compared to RAW264.7 cells

138 R7 by ligands that promote nonphosphorylated LXRalpha S198, and this was lost in LXR-deficient BMDMs.

139 n free access to water, LXRbeta(-/-) but not LXRalpha(-/-) mice exhibited polyuria (abnormal daily ex

140 pha target gene expression as well as Nr1h3 (LXRalpha).

141 ion and mass spectrometry to analyze nuclear LXRalpha complexes and identified poly(ADP-ribose) polym

142 The ability of LXRalpha to dampen energy expenditure in this way provid

143 To determine whether this novel action of LXRalpha has global implications on gene regulation, we

144 ession analysis indicated that activation of LXRalpha affected lipid metabolic networks and increased

145 as an amino acid critical for activation of LXRalpha by oxysterol ligands.

146 Mutations of K432 eliminate activation of LXRalpha by this sirtuin.

147 Activation of LXRalpha in transgenic mice confers a female-specific re

148 In conclusion, the activation of LXRalpha stimulates renin expression and induces MSCs di

149 normally achieved directly by activation of LXRalpha.

150 on of ABC transporters through activation of LXRalpha.

151 stitutive and ligand-dependent activities of LXRalpha.

152 Surprisingly, the constitutive activity of LXRalpha was inhibited by geranylgeraniol, a metabolite

153 Vpr enhanced association of LXRalpha with Lxralpha and Srebp1c promoters, increased

154 XRbeta ko mice, suggesting a contribution of LXRalpha in CNS functions.

155 , or from Apoe-/- mice with BM deficiency of LXRalpha or LXRbeta, into WT recipients.

156 tic LXR agonists, liver-specific deletion of LXRalpha eliminated the detrimental effect of increased

157 Liver-specific deletion of LXRalpha in mice substantially decreased reverse cholest

158 genic background, liver-specific deletion of LXRalpha increased atherosclerosis, uncovering an import

159 onists bound to the ligand binding domain of LXRalpha.

160 ed specifically for the lipogenic effects of LXRalpha and that manipulation of the insulin signaling

161 consistent with anti-atherogenic effects of LXRalpha in the context of FAS deficiency.

162 ogenetic genes, along with the expression of LXRalpha and its target genes sterol regulatory element-

163 cifically, in mice, transgenic expression of LXRalpha in macrophages significantly ameliorated hyperl

164 wild type macrophages, whereas expression of LXRalpha or LXRbeta was similar.

165 Expression of LXRalpha or SPalpha in macrophages inhibits apoptosis in

166 g, and broadly altered hepatic expression of LXRalpha-regulated lipid metabolic genes.

167 e that express a constitutive active form of LXRalpha only in the intestinal epithelium, under the co

168 nhibition by dominant negative (DN) forms of LXRalpha and LXRbeta reduced calcium content in CVCs.

169 To define the function of LXRalpha on gene expression, we transfected the renin-pr

170 show that expression of two target genes of LXRalpha, the ATP-binding cassette (ABC) transporters Ab

171 Identification of LXRalpha as a cAMP-responsive nuclear modulator of renin

172 creases atherosclerosis through induction of LXRalpha and suggest that FAS, which is induced by LXRal

173 Inhibition of LXRalpha could be reversed by addition of mevalonic acid

174 Inhibition of LXRalpha in experimental lung fibrosis and in IPF lung f

175 ory lipids that cause feedback inhibition of LXRalpha in macrophages.

176 Knockdown of LXRalpha/beta by short interfering RNAs completely aboli

177 Knockdown of LXRalpha/beta or SREBP-1c downregulated the expression o

178 of ABCA1 and SREBP-1c genes in the liver of LXRalpha null animals than in treated wild-type controls

179 in a phenotype more specific to the loss of LXRalpha, including hypercorticosteronemia, cholesterol

180 onist was able to compensate for the loss of LXRalpha.

181 m the LiSA to develop a 3D homology model of LXRalpha.

182 Modeling of LXRalpha S198 in the nonphosphorylated and phosphorylate

183 ene selectivity is achieved by modulation of LXRalpha phosphorylation.

184 Overexpression of LXRalpha in As4.1 cells confers cAMP inducibility to rep

185 sponse was dependent more on the presence of LXRalpha than LXRbeta.

186 The increased recruitment of LXRalpha, a Cyp7a1 stimulatory pathway, and decreased ex

187 phorylation in restricting the repertoire of LXRalpha-responsive genes.

188 To study the role of LXRalpha in vivo including the pulmonary function of thi

189 of this study was to investigate the role of LXRalpha on the regulation of rat, human and hamster CYP

190 ese studies further distinguish the roles of LXRalpha and beta and support a growing body of evidence

191 ges in gene expression and identify a set of LXRalpha/cAMP-regulated genes that may have important bi

192 shed Cd36 as a novel transcription target of LXRalpha.

193 hway, as demonstrated by the transfection of LXRalpha siRNA.

194 After stable transfection of LXRalpha, As4.1 cells show a cAMP-inducible up-regulatio

195 Treatment of LXRalpha(-/-)apoE(-/-) mice with synthetic LXR ligand am

196 Igamma-deficient macrophages is dependent on LXRalpha.

197 vity in HEK293-E cells, but had no effect on LXRalpha activity in HEK293-L cells.

198 unsaturated fatty acids had little effect on LXRalpha activity in primary hepatocytes or FTO-2B.

199 aker with respect to potency and efficacy on LXRalpha than on LXRbeta.

200 In macrophages, GW3965 or LXRalpha overexpression significantly suppressed glycate

201 mice that also lacked TLR2, TLR4, MyD88, or LXRalpha intranasally with C. pneumoniae followed by fee

202 age) cells but had no effect on PPARalpha or LXRalpha receptor activity in HEK293-L (late passage) ce

203 s from 293T cells transfected with TRbeta or LXRalpha expression plasmids show that TR, together with

204 es the LXRbeta subtype with selectivity over LXRalpha.

205 lso demonstrating excellent selectivity over LXRalpha.

206 MP stimulation of murine MSCs overexpressing LXRalpha led to their differentiation into JG-like cells

207 ated by treating LXRalpha-/- mice with a pan-LXRalpha/beta agonist.

208 We studied pan-LXRalpha/beta agonists in LXRalpha knockout mice to asse

209 a clinically viable, highly brain-penetrant LXRalpha-partial/LXRbeta-full agonist selectively kills

210 lls expressing wild-type (WT) phosphorylated LXRalpha (RAW-LXRalpha WT).

211 ges were accompanied by increased PPARalpha, LXRalpha, ABCA1 and ABCG1 expressions in the liver.

212 ux and macrophage RCT through the PPARalpha- LXRalpha- ABCA1/G1pathway in vitro and in vivo.

213 e effect of NAMPT knockdown on the PPARalpha-LXRalpha pathway of cholesterol metabolism with MK886 (a

214 transcription factors (SREBP-1c, PPARgamma, LXRalpha) was increased, whereas that of a lipolytic nuc

215 Desmosterol bound to purified LXRalpha and LXRbeta in vitro and supported the recruitm

216 The putative LXRalpha response element (LXRE), identified by chromati

217 s expressing nonphosphorylated LXRalpha (RAW-LXRalpha S198A) compared to RAW264.7 cells expressing wi

218 wild-type (WT) phosphorylated LXRalpha (RAW-LXRalpha WT).

219 ted RAW-LXRalpha S198A cells compared to RAW-LXRalpha WT cells revealed induction of cell migratory a

220 Expression profiling of ligand-treated RAW-LXRalpha S198A cells compared to RAW-LXRalpha WT cells r

221 The nuclear receptor LXRalpha binds oxysterols and mediates feed-forward indu

222 as developed for the orphan nuclear receptor LXRalpha that measures the ligand-dependent recruitment

223 ression and activity of the nuclear receptor LXRalpha, leading to increased hepatic cholesterol and a

224 Liver X receptor (LXRalpha) and RNA polymerase II (RNA Pol II) recruitment

225 aneous coactivation of the liver X receptor, LXRalpha, a nuclear hormone receptor with known roles in

226 ct target of the oxysterol liver X receptor, LXRalpha.

227 demonstrate here that the nuclear receptors LXRalpha and LXRbeta and their oxysterol ligands are key

228 The nuclear receptors LXRalpha and LXRbeta have been implicated in the control

229 The nuclear receptors LXRalpha and LXRbeta have been implicated in the control

230 report that SUMOylation of nuclear receptors LXRalpha and LXRbeta plays a critical role in the transr

231 The nuclear oxysterol receptors LXRalpha (NR1H3) and LXRbeta (NR1H2) coordinately regula

232 ily transcription factors Liver X Receptors (LXRalpha and -beta) are expressed in cartilage, with LXR

233 Liver X receptors (LXRalpha and LXRbeta) are important regulators of choles

234 The liver X receptors (LXRalpha and LXRbeta) are members of the nuclear recepto

235 udies have identified the liver X receptors (LXRalpha and LXRbeta) as important regulators of cholest

236 , we show the role of the liver X receptors (LXRalpha and LXRbeta) in preventing accumulation of free

237 As liver X receptors (LXRalpha,beta) regulate genes linked to lipid and carboh

238 g" nuclear receptors, the liver X receptors (LXRalpha/LXRbeta), protects against atherosclerosis by t

239 The liver X receptors, LXRalpha (NR1H3) and LXRbeta (NR1H2), are ligand-activat

240 Insulin induction of SREBP-1c requires LXRalpha, a nuclear receptor.

241 or Nuclear Receptors (NR) PPARalpha/RXRalpha/LXRalpha, enhance EGFR expression, mediated by the promo

242 s, 21, 27, and 28 were found to be selective LXRalpha agonists, whereas 20, 22, and 25 showed good se

243 tivity approximately 2.2-fold and suppressed LXRalpha activity by 80% (ED50 approximately 25-50 micro

244 ugh a TLR/MyD88-dependent mechanism and that LXRalpha appears to reciprocally modulate and reduce the

245 We conclude that LXRalpha regulates its own expression in human macrophag

246 Additionally we demonstrate that LXRalpha and a subset of LXR target genes are induced du

247 lectromobility shift assays demonstrate that LXRalpha and retinoid X receptor alpha bind to the two L

248 Indeed, our data demonstrated that LXRalpha activation by its ligands or cAMP stimulated re

249 n parallel experiments, we demonstrated that LXRalpha can also bind to the homologous CNRE in the c-m

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

252 These observations indicate that LXRalpha has an essential role in maintaining peripheral

253 ct a recent Nature report that proposed that LXRalpha/beta sense glucose independent of metabolic flu

254 Here, we report that LXRalpha and LXRbeta, two orphan members of the nuclear

255 issue of the JCI, Cummins et al. report that LXRalpha is involved in similar regulation in the adrena

256 Here we report that LXRalpha serine 198 (S198) phosphorylation modulates CCR

257 Here we show that LXRalpha and C/EBPbeta form a complex that can be immuno

258 Here we show that LXRalpha and LXRbeta are expressed in both type I and ty

259 Here, we show that LXRalpha target gene selectivity is achieved by modulati

260 These studies suggest that LXRalpha is not a target for unsaturated fatty acid regu

261 These data suggest that LXRalpha may modulate the bile acid biosynthetic pathway

262 These findings suggest that LXRalpha may represent a central component of a signalin

263 Thus, these data suggest that LXRalpha plays an important role in the regulation of ch

264 The LXRalpha-C/EBPbeta complex is bound to the SREBP-1c prom

265 The LXRalpha/SREBP-1c signaling may play a crucial role in t

266 An inverse correlation between c-FOS and the LXRalpha pathway was also observed in human HCC cell lin

267 ith an LXRalpha agonist, lipogenesis and the LXRalpha target gene expression were significantly reduc

268 terols and is an attractive candidate as the LXRalpha natural hormone.

269 increased in RAW 264.7 cells expressing the LXRalpha S198A phosphorylation-deficient mutant compared

270 However, although re-feeding the LXRalpha ligand induced the immature form of SREBP-1c eq

271 any coactivator/corepressor peptides in the LXRalpha multiplex assay.

272 eta,25-diol 3-sulfate (25HC3S), inhibits the LXRalpha signaling and reduces lipogenesis by decreasing

273 tic LXR ligands induce the expression of the LXRalpha gene in primary human macrophages and different

274 Analysis of the LXRalpha promoter revealed a functional LXR/RXR binding

275 h hLXRalpha or a chimera containing only the LXRalpha ligand binding domain, indicate that a wide arr

276 Our data implied that HLP up-regulated the LXRalpha/ABCA1 pathway, which in turn led to stimulation

277 Our structures show the LXRalpha ligand binding domain in its homodimeric form,

278 n immunoprecipitation assays showed that the LXRalpha-C/EBPbeta complex binds to the SREBP-1c promote

279 st cells use metabolic signaling through the LXRalpha nuclear receptor to defend against Listeria mon

280 In peripheral tissues from these LXRalpha-null mice, LXRbeta activation increases ABCA1 a

281 7 binds to LXRbeta with high affinity and to LXRalpha to a lesser extent, and induces the expression

282 Furthermore, 5,6-EC bound to LXRalpha in a radiolabeled ligand displacement assay (EC

283 a in liver was further evaluated by treating LXRalpha-/- mice with a pan-LXRalpha/beta agonist.

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 hich a constitutively activated LXRalpha (VP-LXRalpha) was inserted into the mouse LXRalpha locus.

288 enovirus-mediated LXR overexpression by VP16-LXRalpha and VP16-LXRbeta accelerated mineralization of

289 When LXRalpha was activated in vivo by inclusion of a non-ste

290 This increase was blunted when LXRalpha and LXRbeta levels were reduced by siRNAs.

291 mouse macrophages cell lines is induced when LXRalpha at S198 is nonphosphorylated.

292 S) and on the regulation of aquaporins while LXRalpha has its most marked effects on cholesterol home

293 d the renin-producing renal As4.1 cells with LXRalpha expression plasmid.

294 t/FAS-deficient bone marrow as compared with LXRalpha-replete/FAS-deficient marrow, consistent with a

295 l-responsive fashion when cotransfected with LXRalpha/RXR or LXRbeta/RXR.

296 Cotransfection with LXRalpha and RXRalpha expression plasmids strongly stimu

297 ese hamster ovary cells, cotransfection with LXRalpha stimulated reporter activity by less than 2-fol

298 AXXAL (L2m) to disrupt its interaction with LXRalpha and ERalpha.

299 n the sterol B-ring results in a ligand with LXRalpha-subtype selectivity.

300 e when apoE null mice were transplanted with LXRalpha-deficient/FAS-deficient bone marrow as compared