DIFFERENTIAL-EFFECTS OF APOLIPOPROTEINS E3 AND E4 ON NEURONAL GROWTH IN-VITRO

DIFFERENTIAL-EFFECTS OF APOLIPOPROTEINS E3 AND E4 ON NEURONAL GROWTH IN-VITRO
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DOI:
10.1126/science.8171342
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发表时间:
1994-05-06
期刊:
影响因子:
56.9
通讯作者:
PITAS, RE
PITAS, RE
中科院分区:
综合性期刊1区
文献类型:
--
作者:
NATHAN, BP;BELLOSTA, S;PITAS, RE

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载脂蛋白E4(apoE 4)是apoE的三种常见亚型之一,与阿尔茨海默病有关。在背根神经节神经元培养中测定apoE对神经元生长的影响。在β-迁移极低密度脂蛋白(β-VLDL)的存在下,apoE 3增加神经突起的生长,而apoE 4减少生长。在β-VLDL存在下,apoE 3或apoE 4的作用可通过与apoE单克隆抗体孵育或apoE还原甲基化来阻止,这两种方法均可阻断apoE与脂蛋白受体相互作用的能力。这些数据表明,受体介导的结合或内化(或两者)的apoE富集的β-VLDL导致异构体特异性的差异,与细胞蛋白质的相互作用,影响神经突生长。
Apolipoprotein E4 (apoE4), one of the three common isoforms of apoE, has been implicated in Alzheimer's disease. The effects of apoE on neuronal growth were determined in cultures of dorsal root ganglion neurons. In the presence of beta-migrating very low density lipoproteins (beta-VLDL), apoE3 increased neurite outgrowth, whereas apoE4 decreased outgrowth. The effects of apoE3 or apoE4 in the presence of beta-VLDL were prevented by incubation with a monoclonal antibody to apoE or by reductive methylation of apoE, both of which block the ability of apoE to interact with lipoprotein receptors. The data suggest that receptor-mediated binding or internalization (or both) of apoE-enriched beta-VLDL leads to isoform-specific differences in interactions with cellular proteins that affect neurite outgrowth.