Abeta Peptide Toxicity is Reduced After Treatments Decreasing Phosphatidylethanolamine Content in Differentiated Neuroblastoma Cells

Abeta Peptide Toxicity is Reduced After Treatments Decreasing Phosphatidylethanolamine Content in Differentiated Neuroblastoma Cells
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DOI:
10.1007/s11064-011-0415-4
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发表时间:
2011-05-01
影响因子:
4.4
通讯作者:
Masserini, Massimo
Masserini, Massimo
中科院分区:
医学3区
文献类型:
--
作者:
Cazzaniga, Emanuela;Bulbarelli, Alessandra;Masserini, Massimo

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我们研究了寡聚淀粉样β肽(A β 1 -42)对分化的人神经母细胞瘤SH-SY 5 Y细胞的毒性是否会受到膜脂质组成变化的影响。一种免疫染色技术,使用从细胞中提取的脂质,并通过薄层色谱法分离,表明Abeta优先结合磷脂酰乙醇胺(PE),细胞提取物中的主要脂质之一。出于这个原因,我们利用假定的磷脂酰乙醇胺生物合成抑制剂(胆碱,磷酸胆碱,R59949)的治疗,以减少其在细胞膜中的比例;胆碱治疗(2.5毫米,24小时)表现出最佳的性能,减少磷脂酰乙醇胺含量从5.7至3.3微克磷/毫克蛋白质。无论是Abeta结合的程度或其毒性降低到胆碱处理的细胞。这些数据可能为开发旨在减少阿尔茨海默病中Abeta毒性的未来策略提供了可能性。
We investigated whether the toxicity of oligomeric amyloid-beta peptide (Abeta1-42) upon differentiated human neuroblastoma SH-SY5Y cells, can be affected by changes of membrane lipid composition. An immunostaining technique, using lipids extracted from the cells and separated by thin layer chromatography, suggested that Abeta preferentially binds to phosphatidylethanolamine (PE), one of the major lipids in the cell extract. For this reason, we utilized treatments with putative inhibitors of phosphatidylethanolamine biosynthesis (choline, phosphocholine, R59949) to decrease its proportion in the cell membrane; choline treatment (2.5 mM, 24 h) showed the best performance, reducing phosphatidylethanolamine content from 5.7 to 3.3 mu g phosphorous/mg protein. Either the extent of Abeta binding or its toxicity decreased onto choline-treated cells. These data may open the possibility to develop future strategies aiming to reduce Abeta toxicity in Alzheimer disease.