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Regulation of Peroxisome Proliferator-Activated Receptor γ Expression by Adipocyte Differentiation and Determination Factor 1/Sterol Regulatory Element Binding Protein 1: Implications for Adipocyte Differentiation and Metabolism 总被引:1,自引:0,他引:1 下载免费PDF全文
Lluis Fajas Kristina Schoonjans Laurent Gelman Jae B. Kim Jamila Najib Genevieve Martin Jean-Charles Fruchart Michael Briggs Bruce M. Spiegelman Johan Auwerx 《Molecular and cellular biology》1999,19(8):5495-5503
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Lipid synthetic transcription factor SREBP-1a activates p21WAF1/CIP1, a universal cyclin-dependent kinase inhibitor 下载免费PDF全文
Inoue N Shimano H Nakakuki M Matsuzaka T Nakagawa Y Yamamoto T Sato R Takahashi A Sone H Yahagi N Suzuki H Toyoshima H Yamada N 《Molecular and cellular biology》2005,25(20):8938-8947
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Sterol regulatory element-binding proteins (SREBPs): transcriptional regulators of lipid synthetic genes 总被引:22,自引:0,他引:22
Shimano H 《Progress in lipid research》2001,40(6):439-452
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Horton JD Shimomura I Ikemoto S Bashmakov Y Hammer RE 《The Journal of biological chemistry》2003,278(38):36652-36660
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Unsaturated fatty acids down-regulate srebp isoforms 1a and 1c by two mechanisms in HEK-293 cells 总被引:13,自引:0,他引:13
Hannah VC Ou J Luong A Goldstein JL Brown MS 《The Journal of biological chemistry》2001,276(6):4365-4372
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Spatial distribution and function of sterol regulatory element-binding protein 1a and 2 homo- and heterodimers by in vivo two-photon imaging and spectroscopy fluorescence resonance energy transfer 下载免费PDF全文
Zoumi A Datta S Liaw LH Wu CJ Manthripragada G Osborne TF Lamorte VJ 《Molecular and cellular biology》2005,25(8):2946-2956
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Dietary polyunsaturated fatty acids and regulation of gene transcription 总被引:18,自引:0,他引:18
Jump DB 《Current opinion in lipidology》2002,13(2):155-164
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SREBP介导的基因表达的调控(英文) 总被引:1,自引:0,他引:1
SREBP转录因子是脂类代谢的重要调节者。当细胞有脂类需求时,在内质网膜上的SREBP前体通过蛋白水解被激活。然后,氨基端的SREBP片段被运到细胞核内激活靶基因的转录。细胞培养和转基因小鼠模型的研究已经证明,SREBP的主要靶基因包括负责脂肪和胆固醇合成的酶,以及低密度脂蛋白受体。早期对SREBP的研究相当完善地揭示了其前体被激活的机理。最近的研究又使我们认识了细胞核内SREBP的调控机理。在细胞核中,SREBP会结合特定的转录辅助因子,刺激或抑制其靶基因的转录,这些转录辅助因子包括CBP/p300和Mediator蛋白复合体。此外,细胞核内SREBP的稳定性受磷酸化和乙酰化的调节。细胞核内SREBP的这种蛋白质相互作用和修饰,使细胞内外信号(如胰岛素或氧化应激)更好地控制脂类合成。在正常生理状态下,脂质动态平衡是严格保持着的,然而,在有些病理条件下,如肥胖、二型糖尿病、心血管疾病和脂肪肝,SREBP往往会失调。因此,SREBP的新调控机制可能对治疗代谢性疾病提供新的机遇。 相似文献
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Sterol regulatory element-binding proteins induce an entire pathway of cholesterol synthesis 总被引:2,自引:0,他引:2
Sakakura Y Shimano H Sone H Takahashi A Inoue N Toyoshima H Suzuki S Yamada N Inoue K 《Biochemical and biophysical research communications》2001,286(1):176-183
To evaluate the effects of sterol regulatory element-binding proteins (SREBPs) on the expression of the individual enzymes in the cholesterol synthetic pathway, we examined expression of these genes in the livers from wild-type and transgenic mice overexpressing nuclear SREBP-1a or -2. As estimated by a Northern blot analysis, overexpression of nuclear SREBP-1a or -2 caused marked increases in mRNA levels of the whole battery of cholesterogenic genes. This SREBP activation covers not only rate-limiting enzymes such as HMG CoA synthase and reductase that have been well established as SREBP targets, but also all the enzyme genes in the cholesterol synthetic pathway tested here. The activated genes include mevalonate kinase, mevalonate pyrophosphate decarboxylase, isopentenyl phosphate isomerase, geranylgeranyl pyrophosphate synthase, farnesyl pyrophosphate synthase, squalene synthase, squalene epoxidase, lanosterol synthase, lanosterol demethylase, and 7-dehydro-cholesterol reductase. These results demonstrate that SREBPs activate every step of cholesterol synthetic pathway, contributing to an efficient cholesterol synthesis. 相似文献
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SREBP transcription factors: master regulators of lipid homeostasis 总被引:41,自引:0,他引:41
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Role of sterol regulatory element-binding protein 1 in regulation of renal lipid metabolism and glomerulosclerosis in diabetes mellitus 总被引:13,自引:0,他引:13
Sun L Halaihel N Zhang W Rogers T Levi M 《The Journal of biological chemistry》2002,277(21):18919-18927
Diabetic renal disease is associated with lipid deposits in the kidney. The purpose of our study was to determine whether there is altered regulation of the sterol regulatory element-binding proteins (SREBPs) in the diabetic kidney and whether SREBPs mediate the abnormal renal lipid metabolism and diabetic renal disease. In streptozotocin-induced diabetes in the rat, there were marked increases in SREBP-1 and fatty acid synthase (FAS) expression, resulting in increased triglyceride (TG) accumulation. Treatment of diabetic rats with insulin prevented the increased renal expression of SREBP-1 and the accumulation of TG. The role of hyperglycemia in the up-regulation of SREBP-1 was confirmed in renal cells cultured in a high glucose media. High glucose induced increased expression of SREBP-1a and -1c mRNA, SREBP-1 protein, and FAS, resulting in increased TG content. To determine a direct role for SREBP in mediating the increase in renal lipids and glomerulosclerosis, we studied SREBP-1a transgenic mice with increased renal expression of SREBP-1. The increase in SREBP-1 was associated with increased expression of FAS and acetyl CoA carboxylase, resulting in increased TG content, increased expression of transforming growth factor beta1 and vascular endothelial growth factor, mesangial expansion, glomerulosclerosis, and proteinuria. Our study therefore indicates that renal SREBP-1 expression is increased in diabetes and that SREBP-1 plays an important role in the increased lipid synthesis, TG accumulation, mesangial expansion, glomerulosclerosis, and proteinuria by increasing the expression of transforming growth factor beta and vascular endothelial growth factor. 相似文献
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