Nathan B P, Chang K C, Bellosta S, Brisch E, Ge N, Mahley R W, Pitas R E
Gladstone Institute of Cardiovascular Disease, University of California, San Francisco 94141-9100, USA.
J Biol Chem. 1995 Aug 25;270(34):19791-9. doi: 10.1074/jbc.270.34.19791.
Evidence is presented for the differential effects of two isoforms of apolipoprotein (apo) E, apoE3 and apoE4, on neurite outgrowth and on the cytoskeleton of neuronal cells (Neuro-2a) in culture. In the presence of a lipid source, apoE3 enhances and apoE4 inhibits neurite outgrowth. Immunocytochemical studies demonstrate that there is a higher concentration of apoE3 than apoE4 in both the cell bodies and neurites. Cells treated with apoE4 showed fewer microtubules and a greatly reduced ratio of polymerized to monomeric tubulin than did cells treated with apoE3. The effect of apoE4 on depolymerization of microtubules was shown by biochemical, immunocytochemical, and ultrastructural studies. The depolymerization of microtubules and the inhibition of neurite outgrowth associated with apoE4 suggest a mechanism whereby apoE4, which has been linked to the pathogenesis of Alzheimer's disease, may prevent normal neuronal remodeling from occurring later in life, when this neurodegenerative disorder develops.
本文提供了证据，证明载脂蛋白（apo）E的两种异构体apoE3和apoE4对培养的神经突生长和神经元细胞（Neuro-2a）的细胞骨架具有不同影响。在有脂质来源的情况下，apoE3促进神经突生长，而apoE4抑制神经突生长。免疫细胞化学研究表明，细胞体和神经突中apoE3的浓度均高于apoE4。与用apoE3处理的细胞相比，用apoE4处理的细胞显示微管数量更少，聚合微管蛋白与单体微管蛋白的比例大大降低。生化、免疫细胞化学和超微结构研究表明了apoE4对微管解聚的作用。微管解聚以及与apoE4相关的神经突生长抑制提示了一种机制，即与阿尔茨海默病发病机制相关的apoE4可能会在这种神经退行性疾病发生的晚年阻止正常的神经元重塑。
