ライフサイエンスコーパス: LXRbeta

1 LXRbeta agonism robustly suppressed tumor growth and met

2 LXRbeta selectivity was confirmed using macrophages deri

3 LXRbeta subsequently modulates signaling by ALK-1 and th

4 LXRbeta targeting significantly prolonged animal surviva

5 LXRbeta was insensitive to fatty acid regulation in both

6 LXRbeta(-/-) mice responded to 24-h dehydration with a d

7 LXRbeta-deficient mice crossed to the hyperlipidemic Apo

8 We propose that (1) LXRbeta and PPARdelta coordinate NPC1L1/ABCA1-dependent

9 Here, we identify 2035 LXRbeta-RXRalpha binding sites containing 4794 LXR respo

10 ti-inflammatory activities and, in addition, LXRbeta is involved in the genesis of dopaminergic neuro

11 R modulator GSK9772 ( 20) as a high-affinity LXRbeta ligand (IC 50 = 30 nM) that shows separation of

12 ll agonist selectively kills GBM cells in an LXRbeta- and cholesterol-dependent fashion, causing tumo

13 l receptors LXR (liver X receptor)-alpha and LXRbeta are nuclear receptors that play a key role in re

14 Liver X receptor (LXR) alpha and LXRbeta function as physiological sensors of cholesterol

15 l receptors liver X receptor (LXR) alpha and LXRbeta.

16 As both ERbeta and LXRbeta are ligand-activated transcription factors, thei

17 Both ERbeta and LXRbeta have potent anti-inflammatory activities and, in

18 of cofactor peptides onto both LXRalpha and LXRbeta and showed an EC(50) of approximately 2 muM in p

19 here that the nuclear receptors LXRalpha and LXRbeta and their oxysterol ligands are key regulators o

20 eceptors liver X receptor (LXR) LXRalpha and LXRbeta are differentially expressed ligand-activated tr

21 Here we show that LXRalpha and LXRbeta are expressed in both type I and type II mouse l

22 istochemical staining that both LXRalpha and LXRbeta are expressed in the cell nuclei of the epitheli

23 demonstrate here that although LXRalpha and LXRbeta are not required for adipocyte development per s

24 confirmed that 4 binds to both LXRalpha and LXRbeta directly and recruits coactivator peptide SRC-1.

25 derived from mice lacking both LXRalpha and LXRbeta failed to up-regulate the expression of ABC8 fol

26 The nuclear receptors LXRalpha and LXRbeta have been implicated in the control of cholester

27 The nuclear receptors LXRalpha and LXRbeta have been implicated in the control of lipogenes

28 of the liver X receptors (LXRs) LXRalpha and LXRbeta in carbohydrate sensing by the liver (see the re

29 confirm an equivalent role for LXRalpha and LXRbeta in the regulation of ABCA1 and SREBP-1c gene exp

30 Desmosterol bound to purified LXRalpha and LXRbeta in vitro and supported the recruitment of steroi

31 at the liver X receptors (LXRs) LXRalpha and LXRbeta inhibit basal and cytokine-inducible expression

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

33 UMOylation of nuclear receptors LXRalpha and LXRbeta plays a critical role in the transrepression of

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

35 Both LXRalpha and LXRbeta transactivated the VEGF promoter in transient tr

36 Both LXRalpha and LXRbeta were present in VSMC, and their activation with

37 receptor coactivator-1 to human LXRalpha and LXRbeta with EC(50)s of 40 nM, profiles as an LXR agonis

38 Liver X receptors (LXRalpha and LXRbeta) are important regulators of cholesterol and lip

39 ver X receptors alpha and beta (LXRalpha and LXRbeta) are important regulators of cholesterol homeost

40 The liver X receptors (LXRalpha and LXRbeta) are members of the nuclear receptor superfamily

41 entified the liver X receptors (LXRalpha and LXRbeta) as important regulators of cholesterol and lipi

42 role of the liver X receptors (LXRalpha and LXRbeta) in preventing accumulation of free cholesterol

43 iver X receptors alpha and beta(LXRalpha and LXRbeta), which are important in regulating not only lip

44 ver X receptors alpha and beta (LXRalpha and LXRbeta).

45 is lost in animals lacking both LXRalpha and LXRbeta, confirming the critical role of these receptors

46 oxidized lipids, which activate LXRalpha and LXRbeta, resulting in the induction of ABCA1, ABCG1, and

47 Here, we report that LXRalpha and LXRbeta, two orphan members of the nuclear receptor supe

48 Plaques from both LXRalpha and LXRbeta-deficient Apoe-/- mice exhibited impaired regres

49 iring the participation of both LXRalpha and LXRbeta.

50 ct, PARP-1 interacted with both LXRalpha and LXRbeta.

51 eptors liver X receptor alpha (LXRalpha) and LXRbeta function as physiological receptors for oxidized

52 iver X receptor alpha (LXRalpha) (NR1H3) and LXRbeta (NR1H2) are important regulators of genes involv

53 ear oxysterol receptors LXRalpha (NR1H3) and LXRbeta (NR1H2) coordinately regulate the expression of

54 The liver X receptors, LXRalpha (NR1H3) and LXRbeta (NR1H2), are ligand-activated transcription fact

55 ective agonist for both LXRalpha (NR1H3) and LXRbeta (NR1H2).

56 re Fugu orthologs, excepting CAR (NR1I3) and LXRbeta (NR1H2).

57 Both LXRalpha/RXRalpha and LXRbeta/RXRalpha transactivated the CETP promoter via it

58 TRalpha and LXRbeta bind to identical response elements on DNA and s

59 In both WT and LXRbeta(-/-) mice, expression of TRalpha was high at pos

60 the same degree of potency as 22R-HC (3) at LXRbeta, while it was virtually inactive at LXRalpha (EC

61 t, orally efficacious liver X receptor beta (LXRbeta) agonist (17).

62 lear receptor family, liver X receptor beta (LXRbeta) and thyroid hormone receptor alpha (TRalpha), h

63 the nuclear receptor liver X receptor beta (LXRbeta) as a modulator/mediator of ALK-1 signaling.

64 udies have implicated liver X receptor beta (LXRbeta) in key neurodevelopmental processes and neurode

65 he oxysterol receptor liver X receptor beta (LXRbeta) in the etiology of diabetes insipidus (DI).

66 Liver X receptor beta (LXRbeta) is a member of the nuclear receptor super gene

67 creased expression of liver X receptor beta (LXRbeta), a nuclear receptor that controls cellular lipi

68 the nuclear receptor, liver X receptor beta (LXRbeta), had an adverse effect on progression of the di

69 tor beta (ERbeta) and liver X receptor beta (LXRbeta).

70 athway activation in macrophages achieved by LXRbeta and endogenous ligand is unable to maintain home

71 nts revealed these effects to be mediated by LXRbeta, which elicits these outcomes through transcript

72 female mice, we found that LXRs, especially LXRbeta, also repress the browning process of subcutaneo

73 ated transcriptional responses, establishing LXRbeta as a potential modulator/mediator of ALK-1/ALK-2

74 ction in all members of the NR family except LXRbeta suggests a functional role for the intron.

75 gnition tests to evaluate behavior in female LXRbeta KO (LXRbeta(-/-)) mice.

76 lude that the anxiogenic phenotype in female LXRbeta(-/-) mice is caused by reduced GABAergic input f

77 We found that the female LXRbeta(-/-) mice were anxious with impaired behavioral

78 ompounds displayed good binding affinity for LXRbeta and LXRalpha and were potent activators in LBD t

79 Compound 13 demonstrated partial agonism for LXRbeta in kidney HEK-293 cells but did not activate Gal

80 Our data establish novel roles for LXRbeta in adipocyte growth, glucose homeostasis, and be

81 ignificantly decreased in skin isolated from LXRbeta-null mice.

82 dney HEK-293 cells but did not activate Gal4 LXRbeta fusion proteins in huh-7 liver cells.

83 skin, we mapped its cistrome by identifying LXRbeta-RXRalpha binding sites using ChIP-on-chip in nor

84 Importantly, LXRbeta activation displayed melanoma-suppressive cooper

85 In LXRbeta(-/-) mice the expression of AVP was markedly dec

86 imilar food intake and oxygen consumption in LXRbeta-/- mice suggests that reduced storage of lipid i

87 dition, 22ROH did not reduce inflammation in LXRbeta-/- or LXRalphabeta-/- animals, indicating that L

88 nserved lysine (K432 in LXRalpha and K433 in LXRbeta) adjacent to the ligand-regulated activation dom

89 ER2) (the reelin receptor) was much lower in LXRbeta(-/-) than in WT mice.

90 retarded migration of later-born neurons in LXRbeta(-/-) mice but that as thyroid hormone (TH) incre

91 there is reduced OPC production from RGCs in LXRbeta(-/-) mice.

92 s to evaluate behavior in female LXRbeta KO (LXRbeta(-/-)) mice.

93 Mice lacking LXRbeta exhibit lymphoid hyperplasia and enhanced respon

94 the two isoforms of Liver X receptor (LXR), LXRbeta has been shown to have major effects in the cent

95 LXRalpha(-/-), LXRbeta(-/-), and LXRalpha/beta(-/-) mice developed acel

96 the LXR agonist GW3965 and in LXRalpha(-/-), LXRbeta(-/-), and LXRalpha/beta(-/-) mice.

97 LXRalpha, LXRbeta, ATP-binding cassette transporter A1 (ABCA1), an

98 and T0901317 required PPARalpha and LXRalpha/LXRbeta for statistical significance.

99 es from the livers of wild-type and LXRalpha/LXRbeta-null mice after exposure to the LXR agonist N-(2

100 r receptors, the liver X receptors (LXRalpha/LXRbeta), protects against atherosclerosis by transcript

101 In the brain of WT mice LXRbeta was expressed in the nuclei of magnocellular neu

102 heral tissues from these LXRalpha-null mice, LXRbeta activation increases ABCA1 and SREBP-1c gene exp

103 al docking studies using GLIDE with modified LXRbeta ligand-binding domain (LBD) on internal compound

104 Activation of LXRbeta and/or PPARdelta in cholangiocytes induces ATP-b

105 XR activation promoted the direct binding of LXRbeta to the ligand-binding domain of ERalpha and init

106 knockout mice to assess the contribution of LXRbeta to the regulation of selected target genes.

107 normalities were detectable in the cortex of LXRbeta(-/-) mice and ApoER2 expression was much stronge

108 still abundantly expressed in the cortex of LXRbeta(-/-) mice.

109 myelination, and point to the involvement of LXRbeta in psychiatric disorders.

110 n in aquaporin-1 expression in the kidney of LXRbeta(-/-) mice.

111 ts mitogen-driven expansion, whereas loss of LXRbeta confers a proliferative advantage.

112 Here, we demonstrate that loss of LXRbeta function leads to abnormality in locomotor activ

113 ocytes was higher in the substantia nigra of LXRbeta(-/-) mice than in WT littermates.

114 aminergic neurons of the substantia nigra of LXRbeta(-/-) mice were much more severely affected by MP

115 t results in the specific phosphorylation of LXRbeta by ALK-1, primarily on serine residues.

116 th IL-1beta, indicating a protective role of LXRbeta in cartilage.

117 The in vivo role of LXRbeta in liver was further evaluated by treating LXRal

118 Starting with a crystal structure of LXRbeta and a docked 2-(methylsulfonyl)benzyl alcohol fr

119 activated ALK-1 results in translocation of LXRbeta from the nuclear compartment to the cytoplasmic

120 del of PD to investigate the possible use of LXRbeta as a target for prevention or treatment of PD.

121 to potency and efficacy on LXRalpha than on LXRbeta.

122 crophages, whereas expression of LXRalpha or LXRbeta was similar.

123 oe-/- mice with BM deficiency of LXRalpha or LXRbeta, into WT recipients.

124 hion when cotransfected with LXRalpha/RXR or LXRbeta/RXR.

125 pairs) as a binding site for LXRalpha/RXR or LXRbeta/RXR.

126 ble, highly brain-penetrant LXRalpha-partial/LXRbeta-full agonist selectively kills GBM cells in an L

127 nuclear receptors, some of which (PPARalpha, LXRbeta) regulate specific liver gene expression network

128 t required for adipocyte development per se, LXRbeta is required for the increase in adipocyte size t

129 In summary, selective LXRbeta activation is expected to stimulate ABCA1 gene e

130 e that it is possible to achieve significant LXRbeta selectivity in a small molecule while maintainin

131 Surprisingly, LXRbeta was not expressed in the neurons of the substant

132 rt for drug development strategies targeting LXRbeta.

133 endent more on the presence of LXRalpha than LXRbeta.

134 These studies demonstrate that LXRbeta has nonnuclear function in EC caveolae/lipid raf

135 endothelial cells (ECs) and discovered that LXRbeta has nonnuclear function and stimulates EC migrat

136 optic nerve, providing in vivo evidence that LXRbeta deletion delays both oligodendrocyte differentia

137 or LXRalphabeta-/- animals, indicating that LXRbeta is required for this anti-inflammatory effect.

138 Further studies revealed that LXRbeta and ERalpha are colocalized and functionally cou

139 alysis of islet gene expression reveals that LXRbeta is required for expression of the cholesterol tr

140 Collectively, these results suggest that LXRbeta, by driving RGCs to become OPCs in the dorsal co

141 ncrease in urine osmolality, suggesting that LXRbeta is a key receptor in controlling water balance w

142 Cholesterol-efflux studies verify that LXRbeta can drive apoA1-dependent cholesterol mobilizati

143 eceptor (LXR) agonist (2) that activates the LXRbeta subtype with selectivity over LXRalpha.

144 in NHEKs, demonstrating that 77% of all the LXRbeta-RXRalpha binding regions show the presence of AP

145 , 22, and 25 showed good selectivity for the LXRbeta isoform.

146 NS phenotype is much more severe than in the LXRbeta ko mice, suggesting a contribution of LXRalpha i

147 The reason for the migration defect in the LXRbeta(-/-) mouse and the possibility that TRalpha may

148 A comparison with existing structures of the LXRbeta homodimer and LXRalpha:RXR (retinoid X receptor)

149 cis-regulatory motifs in the vicinity of the LXRbeta-RXRalpha binding sites.

150 Despite reduced amounts of adipose tissue, LXRbeta-/- mice on a chow diet have insulin sensitivity

151 lthough 13 showed potent binding affinity to LXRbeta (IC(50) = 53 nM), it had little binding affinity

152 An i.p. injection of AVP to LXRbeta(-/-) mice revealed a partial kidney response: Th

153 region of the human C3 gene, which binds to LXRbeta in macrophages but not in HepG2 cells.

154 lasmic domain of ALK-1 specifically binds to LXRbeta in vitro and in vivo.

155 Compound 17 binds to LXRbeta with high affinity and to LXRalpha to a lesser e

156 the structurally related analog 19 bound to LXRbeta reveals regions within the receptor that can aff

157 ated carotid artery reendothelialization via LXRbeta- and ERalpha-dependent processes.

158 LXR overexpression by VP16-LXRalpha and VP16-LXRbeta accelerated mineralization of CVCs.

159 Given free access to water, LXRbeta(-/-) but not LXRalpha(-/-) mice exhibited polyur

160 The interaction of activated ALK-1 with LXRbeta in the cytoplasmic compartment results in the sp

161 and -beta) are expressed in cartilage, with LXRbeta being the predominant isoform.