共查询到20条相似文献,搜索用时 31 毫秒
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Direct interaction of nuclear liver X receptor-beta with ABCA1 modulates cholesterol efflux 总被引:1,自引:0,他引:1
Hozoji M Munehira Y Ikeda Y Makishima M Matsuo M Kioka N Ueda K 《The Journal of biological chemistry》2008,283(44):30057-30063
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Madsen L Petersen RK Steffensen KR Pedersen LM Hallenborg P Ma T Frøyland L Døskeland SO Gustafsson JA Kristiansen K 《The Journal of biological chemistry》2008,283(33):22723-22736
The biological functions of liver X receptors (LXRs) alpha and beta have primarily been linked to pathways involved in fatty acid and cholesterol homeostasis. Here we report a novel role of LXR activation in protecting cells from statin-induced death. When 3T3-L1 preadipocytes were induced to differentiate by standard isobutylmethylxanthine/dexamethasone/insulin treatment in the presence of statins, they failed to differentiate and underwent massive apoptosis. The simultaneous addition of selective LXR agonists prevented the statin-induced apoptosis. By using mouse embryo fibroblasts from wild-type (LXRalpha+/+/LXRbeta+/+), LXRalpha knock-out mice (LXRalpha(-/-)/LXRbeta+/+), LXRbeta knock-out mice (LXRalpha+/-/LXRbeta(-/-)), and LXR double knock-out mice (LXRalpha(-/-)/LXRbeta(-/-)) as well as 3T3-L1 cells transduced with retroviruses expressing either wild-type LXRalpha or a dominant negative version of LXRalpha, we demonstrate that the response to LXR agonists is LXR-dependent. Interestingly, LXR-mediated rescue of statin-induced apoptosis was not related to up-regulation of genes previously shown to be involved in the antiapoptotic action of LXR. Furthermore, forced expression of Bcl-2 did not prevent statin-induced apoptosis; nor did LXR action depend on protein kinase B, whose activation by insulin was impaired in statin-treated cells. Rather, LXR-dependent rescue of statin-induced apoptosis in 3T3-L1 preadipocytes required NF-kappaB activity, since expression of a dominant negative version of IkappaBalpha prevented LXR agonist-dependent rescue of statin-induced apoptosis. Thus, the results presented in this paper provide novel insight into the action of statins on and LXR-dependent inhibition of apoptosis. 相似文献
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Zhang Y Repa JJ Gauthier K Mangelsdorf DJ 《The Journal of biological chemistry》2001,276(46):43018-43024
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Identification of liver X receptor-retinoid X receptor as an activator of the sterol regulatory element-binding protein 1c gene promoter 总被引:18,自引:0,他引:18
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Yoshikawa T Shimano H Amemiya-Kudo M Yahagi N Hasty AH Matsuzaka T Okazaki H Tamura Y Iizuka Y Ohashi K Osuga J Harada K Gotoda T Kimura S Ishibashi S Yamada N 《Molecular and cellular biology》2001,21(9):2991-3000
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The phospholipid transfer protein gene is a liver X receptor target expressed by macrophages in atherosclerotic lesions
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Laffitte BA Joseph SB Chen M Castrillo A Repa J Wilpitz D Mangelsdorf D Tontonoz P 《Molecular and cellular biology》2003,23(6):2182-2191
The liver X receptors (LXRs) are members of the nuclear receptor superfamily that are activated by oxysterols. In response to ligand binding, LXRs regulate a variety of genes involved in the catabolism, transport, and uptake of cholesterol and its metabolites. Here we demonstrate that LXRs also regulate plasma lipoprotein metabolism through control of the phospholipid transfer protein (PLTP) gene. LXR ligands induce the expression of PLTP in cultured HepG2 cells and mouse liver in vivo in a coordinate manner with known LXR target genes. Moreover, plasma phospholipid transfer activity is increased in mice treated with the synthetic LXR ligand GW3965. Unexpectedly, PLTP expression was also highly inducible by LXR in macrophages, a cell type not previously recognized to express this enzyme. The ability of synthetic and oxysterol ligands to regulate PLTP mRNA in macrophages and liver is lost in animals lacking both LXRalpha and LXRbeta, confirming the critical role of these receptors. We further demonstrate that the PLTP promoter contains a high-affinity LXR response element that is bound by LXR/RXR heterodimers in vitro and is activated by LXR/RXR in transient-transfection studies. Finally, immunohistochemistry studies reveal that PLTP is highly expressed by macrophages within human atherosclerotic lesions, suggesting a potential role for this enzyme in lipid-loaded macrophages. These studies outline a novel pathway whereby LXR and its ligands may modulate lipoprotein metabolism. 相似文献
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Costet P Lalanne F Gerbod-Giannone MC Molina JR Fu X Lund EG Gudas LJ Tall AR 《Molecular and cellular biology》2003,23(21):7756-7766
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