Modulation of nitric oxide production in human macrophages by apolipoprotein-E and amyloid-beta peptide.
Modulation of nitric oxide production in human macrophages by apolipoprotein-E and amyloid-beta peptide.
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载脂蛋白-E 和淀粉样蛋白-β 肽调节人巨噬细胞中一氧化氮的产生。
DOI：
10.1006/bbrc.1997.7408
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发表时间：
1997
影响因子：
3.1
通讯作者：
Colton,CA
中科院分区：
文献类型：
--
作者：
Vitek,MP;Snell,J;Dawson,H;Colton,CA
氧化应激的诱导被认为是阿尔茨海默病等慢性神经退行性疾病的致病因素。载脂蛋白-E(ApoE)和淀粉样蛋白-β-eta肽(A-β)已被报道可改变大脑的氧化还原状态。以人单核细胞来源的巨噬细胞作为脑小胶质细胞模型，发现生理水平的载脂蛋白-E可刺激多肌苷：多胞苷(Poly I：C)刺激细胞产生一氧化氮(NO)。APOE处理的细胞释放的NO比单独用Poly I：C处理的细胞多68%，比未激活的细胞释放的NO多近三倍。与小鼠小胶质细胞不同，无论有没有Poly I：C处理，人类细胞都不能对Aβ多肽产生NO。此外，Aβ与apoE联合使用可抑制apoE诱导的NO生成增加。由于阿尔茨海默病与APOE4等位基因的存在密切相关，我们的研究预测了一种机制，即载脂蛋白E和Aβ调节人脑中一氧化氮的产生。
Induction of oxidative stress has been implicated as a causative factor in chronic neurodegenerative diseases such as Alzheimer's disease. Apolipoprotein-E (apoE) and amyloid-βeta peptide (Aβ) have been reported to alter the redox state of the brain. Using human monocyte-derived macrophages as a model of brain microglia, physiological levels of apolipoprotein-E were found to stimulate nitric oxide (NO) production in polyinosinic:polycytidylic acid (poly I:C) primed cells. ApoE treatment released 68% more NO than cells treated with poly I:C alone and almost threefold more NO than unprimed cells. In contrast to mouse microglia, human cells failed to generate NO in response to Aβ peptides, with or without poly I:C treatments. Furthermore, the combination of Aβ plus apoE inhibited the increase in NO production induced by apoE. Since Alzheimer's is strongly associated with the presence of anAPOE4allele, our study predicts a mechanism where apoE and Aβ regulate nitric oxide production in human brain.