The role of cholesterol in the biosynthesis of β-amyloid.
The role of cholesterol in the biosynthesis of β-amyloid.
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DOI：
10.1097/00001756-199906030-00014
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发表时间：
1999-06-03
期刊：
影响因子：
1.7
通讯作者：
Austen, BM
中科院分区：
文献类型：
--
作者：
Frears, ER;Stephens, DJ;Austen, BM
向用淀粉样前体蛋白（APP）转染的人HEK细胞中加入β-羟基-β-甲基戊二酰-CoA（HmG-CoA）还原酶抑制剂洛伐他汀，可使细胞内胆固醇/蛋白质比率降低50%，并显著抑制新合成APP的β-分泌酶裂解。浓度为200 μ g/ml的外源性水溶性胆固醇使新合成的β-淀粉样蛋白生成产物增加4倍。这些细胞内的变化是可检测的免疫沉淀和免疫荧光标记。通过蛋白芯片阵列上的N-末端抗β-淀粉样蛋白抗体从培养基中捕获并使用表面增强激光解吸/电离（SELDI）质谱法检测的片段的分析显示，用胆固醇（200 μ g/ml）培养使β-淀粉样蛋白1-40的分泌增加1.8倍，并使β-淀粉样蛋白1-42的分泌增加。胆固醇对APP加工的改变可能介导ApoE 4等位基因增加西方人群患阿尔茨海默病（AD）风险的方式。NeuroReport 10：1699-1705（C）1999 Lippincott威廉姆斯和威尔金斯。
ADDITION of the beta-hydroxy-beta-methylglutaryl-CoA (HmG-CoA) reductase inhibitor lovastatin to human HEK cells transfected with the amyloid precursor protein (APP) reduces intracellular cholesterol/protein ratios by 50%, and markedly inhibits beta-secretase cleavage of newly-synthesized APP. Exogenous water-solubilized cholesterol at 200 mu g/ml concentration increases newly synthesized beta-amyloidogenic products four-fold. These intracellular changes are detectable by immunoprecipitation and immunofluorescent labelling. Analyses of the fragments captured from culture medium by an N-terminal anti-beta-amyloid antibody on ProteinChip arrays and detected using surface-enhanced laser desorption/ionization (SELDI) mass spectrometry revealed that culture with cholesterol (200 mu g/ml) increased secretion of beta-amyloid 1-40 by 1.8-fold, and increased secretion of beta-amgloid 1-42. Changes in APP processing by cholesterol may mediate the way in which the ApoE4 allele increases risk of developing Alzheimer's disease (AD) in western populations. NeuroReport 10:1699-1705 (C) 1999 Lippincott Williams & Wilkins.