Isomerization of Asp7 increases the toxic effects of amyloid β and its phosphorylated form in SH-SY5Y neuroblastoma cells
Isomerization of Asp7 increases the toxic effects of amyloid β and its phosphorylated form in SH-SY5Y neuroblastoma cells
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DOI：
10.1134/s0026893316050034
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发表时间：
2016-09-01
影响因子：
1.2
通讯作者：
Mitkevich, V. A.
中科院分区：
文献类型：
--
作者：
Barykin, E. P.;Petrushanko, I. Yu.;Mitkevich, V. A.
老年斑和淀粉样原纤维形成过程中β淀粉样蛋白（Aβ）毒性低聚物的产生被认为在阿尔茨海默病的发病和进展中发挥着核心作用。 β 的产生是一个生理过程，但触发致病性 A β 聚集转变的因素仍然未知。 A beta 的翻译后修饰可能会诱导这种转变。在 SH-SY5Y 人神经母细胞瘤细胞中研究了 A beta 及其含有异构化 Asp7、磷酸化 Ser8 或两者的修饰形式的作用。 Asp7 异构化可增加完整 A β 和磷酸化 A β 的细胞毒性。细胞毒性的增加与含有异构化 Asp7 的 Aβ 的内化增加或对线粒体功能的影响或谷胱甘肽和活性氧水平的降低无关。一氧化氮 (NO) 水平被确定为含异构化 Asp7 的肽的细胞毒性作用的决定因素，NO 水平的降低与细胞毒性的增加相关。
The generation of amyloid beta (A beta) toxic oligomers during the formation of senile plaques and amyloid fibrils is thought to play a central role in the onset and progression of Alzheimer's disease. A beta production is a physiological process, but the factors that trigger a transition to pathogenic A beta aggregation remain unknown. Posttranslational modifications of A beta could potentially induce the transition. The effects of A beta and its modified forms containing isomerized Asp7, phosphorylated Ser8, or both, were studied in SH-SY5Y human neuroblastoma cells. Asp7 isomerization of was shown to increase cytotoxicity of both the intact and phosphorylated A beta. An increase in cytotoxicity was not associated with an increased internalization of the isomerized Asp7-containing A beta or an influence on the function of mitochondria or reduced glutathione and reactive oxygen species levels. The nitric oxide (NO) level was identified as a determinant of the cytotoxic effect of isomerized Asp7-containing peptides, a decrease in NO level correlating with an increase in cytotoxicity.