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TO901317对海马神经元β-分泌酶表达及β-淀粉样肽生成的影响 被引量:1

The effect of TO901317 on the expression of β-secretase and β-amyloid peptide in hippocampal neuron
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摘要 目的研究肝X受体(LXR)配体TO901317对海马神经元淀粉样前体蛋白(APP)、α-分泌酶(ADAM10)和β-分泌酶(BACE1)mRNA表达的影响及与β-淀粉样肽(Aβ)生成的关系。方法大鼠海马神经元培养至第7天,在饲养液中加入2.0μmol/LTO901317,继续培养48h。应用RT-PCR方法研究海马神经元APP、ADAM10和BACE1等基因的mRNA的表达,放免法检测培养液Aβ含量的变化。结果TO901317降低海马神经元APP和BACE1 mRNA表达(P<0.01),减少培养液Aβ含量(P<0.01),但不影响ADAM10 mRNA表达(P>0.05)。结论TO901317激活LXR,能通过降低APP和BACE1的表达来减少海马神经元Aβ分泌。 Objective To investigate the effects of liver X receptor(LXR) ligand TO901317-LXR on the expression of β-amyloid precursor protein (APP) ,α-secretase (ADAM10) and β-secretase ( BACE1 ) in hippocampal neuron. Methods On the 7 th day ,hippocampal neurons were treated with 2.0 μmol/L TO901317. The expression of APP,ADAM10 and BACE1 mRNA were measured by RT-PCR and the content of Aβ in culture fluid was measured by radioimmunoassay method after cultured 48 h. Results TO901317 decreased the expression of APP and BACE1 mRNA (P 〈 0. 01 ) and the content of Aβ( P 〈 0, 01 )significantly, but had no effect on the expression of ADAM10 mRNA ( P 〉 0. 05 ). Conclusions TO901317 could activate LXR and decrease the secretion of Aβ by decreasing the expression of APP and BACE1 mRNA in hippocampal neuron.
出处 《中国老年学杂志》 CAS CSCD 北大核心 2007年第20期1953-1955,共3页 Chinese Journal of Gerontology
基金 国家自然科学基金(30371566) 河北省自然科学基金(303472)
关键词 肝X受体 TO901317 β-淀粉样肽前体蛋白 Β-分泌酶 Β-淀粉样肽 Liver X receptor TOg01317 β-amyloid precursor protein β-secretase β-amyloid peptide
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  • 1Howland DS,Trusko SP,Savage MJ,et al.Modulation of secreted betaamyloid precursor protein and amyloid beta-peptide in brain by cholesterol[J].J Biol Chem,1998;273(26):16576-82.
  • 2Selkoe DJ,Schenk D.Alzheimer's disease:molecular understanding predicts amyloid-based therapeutics[J].Ann Rev Pharmacol Toxicol,2003;43:545-84.
  • 3Oltersdorf T,Fritz LC,Schenk DB,et al.The secreted form of the Alzheimer's amyloid precursor protein with the Kunitz domain is protease nexinⅡ[J].Nature,1989;341(6238):144-7.
  • 4Yanagisawa K,Matsuzaki K.Cholesterol-dependent aggregation of amyloid beta-protein[J].Ann N Y Acad Sci,2002;977(10):384-6.
  • 5Simons M,Keller P,de Strooper B,et al.Cholesterol depletion inhibia the generation of β-amyloid in hippocampal neurons[J].Proc Natl Acad Sci USA,1998;95(11):6460-4.
  • 6Koldamova RP,Lefterov IM,Staufenbiel M,et al.The liver X receptor ligand TO901317 decreases amyloid beta production in vitro and in a mouse model of Alzheimer's disease[J].J Biol Chem,2005;280(6):4079-88.
  • 7YangY,Quitschke WW,Vostrov AA,et al.CTCF is essential for up-regulating expression from the amyloid precursor protein promoter during differentiation of primary hippocampal neurons[J].J Neurochem,1999;73(6):2286-98.
  • 8Galbete JL,Martin TR,Peressini E,et al.Cholesterol decreases secretion of the secreted form of amyloid precursor protein by interfering with glycosylation in the protein secretory pathway[J].Biochem J,2000;348(2):307-13.
  • 9Harada H,Tamaoka A,Ishii K,et al.Beta-site APP cleaving enzyme 1(BACE1)is increased in remaining neurons in Alzheimer's disease brains[J].Neurosci Res,2006;54(1):24-9.
  • 10Rebeck GW.Cholesterol efflux as a critical component of Alzheimer'sdisease pathogenesis[J].J Mol Neurosci,2004;23(3):219-24.

同被引文献7

  • 1Yanagisawa K, Matsuzaki K. Cholesterol-dependent aggregation of amyloid beta-protein[ J]. Ann N Y Acad Sci ,2002 ;977:384-6.
  • 2Chinetti G, Lestavel S, Bocher V, et al. PPAR-alpha and PPAR-gamma activators induce cholesterol removal from human macrophage foam ceils through stimulation of the ABCA1 pathway [ J ]. Nat Med, 2001 ; 7 ( 1 ) : 53-8.
  • 3Chinetti-Gbaguidi G, Rigamonti E, Helin L, et al. Peroxisome proliferatoractivated receptor alpha controls cellular cholesterol trafficking in macrophages[ J]. J Lipid Res,2005 ;46(12) :2717-25.
  • 4Cimini A, Benedetti E, Cristiano L,et al. Expression of peroxisome preliferator-activated receptors (PPARs) and retinoic acid receptors (RXRs) in rat cortical neurons[J]. Neuroscience,2005 ;130(2) :325-37.
  • 5Yoshikawa T, Ide T, Shimano H, et al. Cross-talk between peroxisome proliferator-activated receptor (PPAR) alpha and liver X receptor (LXR) in nutritional regulation of fatty acid metabolism. I. PPARs suppress sterel regulatory element binding protein-1c promoter through inhibition of LXR signaling [J]. Mol Endoerinol, 2003 ; 17 ( 7 ) : 1240-54.
  • 6Koldamova RP, Lefterov IM,Staufenbiel M, et al. The liver X receptor ligand T0901317 decreases amyloid beta production in vitro and in a mouse model of Alzheimer's disease[ J ]. J Biol Chem,2005 ;280 (6) :4079-88.
  • 7Marx J. Alzheimer' s disease. Bad for the heart, bad for the mind [ J]? Science,2001 ;294 ( 5542 ) : 508-9.

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