Effect of the lipid peroxidation product acrolein on tau phosphorylation in neural cells
Effect of the lipid peroxidation product acrolein on tau phosphorylation in neural cells
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DOI：
10.1002/jnr.10525
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发表时间：
2003-03-15
影响因子：
4.2
通讯作者：
Avila, J
中科院分区：
文献类型：
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作者：
Gómez-Ramos, A;Díaz-Nido, J;Avila, J
包括阿尔茨海默病和tau病在内的几种神经退行性疾病的一个标志是微管相关蛋白tau的过度磷酸化。分别使用抗体PHF1和12E8检测了脯氨酸导向和非脯氨酸导向蛋白激酶对Tau蛋白的磷酸化作用。研究了脂质过氧化产物丙烯醛对这些磷酸化模式的影响。我们发现丙烯醛，花生四烯酸的过氧化产物，在人类神经母细胞瘤细胞和小鼠胚胎皮层神经元的原代培养中，增加了PHF-1识别位点的tau磷酸化。然而，tau蛋白在PHF1位点的基础磷酸化似乎主要是由糖原合成酶激酶-3介导的（它也在对β肽的反应中被激活），丙烯醛诱导的tau蛋白在同一位点的过度磷酸化也是由于p38应激激活的激酶。这些结果支持了氧化应激和随后形成的脂质过氧化产物可能在阿尔茨海默病和tau病中促进tau蛋白磷酸化的观点。(C) 2002 Wiley-Liss, Inc。
A hallmark of several neurodegenerative disorders, including Alzheimer's disease and tauopathies, is the hyperphosphorylation of the microtubule-associated protein tau. Tau phosphorylation by proline-directed and non-proline-directed protein kinases has been tested using antibodies PHF1 and 12E8, respectively. The effect of the lipid peroxidation product acrolein on these modes of phosphorylation has been assayed. We have found that acrolein, a peroxidation product from arachidonic acid, increases the phosphorylation of tau at the site recognized by PHF-1 both in human neuroblastoma cells and in primary cultures of mouse embryo cortical neurons. Whereas the basal phosphorylation of tau protein at the PHF1 site seems to be largely mediated by glycogen synthase kinase-3 (which is also activated in response to Abeta peptide), the acrolein-induced tau hyperphosphorylation at the same site is also due to p38 stress-activated kinase. These results support the view that oxidative stress and subsequent formation of lipid peroxidation products may contribute to tau protein phosphorylation in Alzheimer's disease and tauopathies. (C) 2002 Wiley-Liss, Inc.