Effects of 4-hydroxy-nonenal and Amyloid-beta on expression and activity of endothelin converting enzyme and insulin degrading enzyme in SH-SY5Y cells.
Effects of 4-hydroxy-nonenal and Amyloid-beta on expression and activity of endothelin converting enzyme and insulin degrading enzyme in SH-SY5Y cells.
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DOI：
10.3233/jad-2009-1066
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Wang DS
中科院分区：
文献类型：
--
作者：
Wang R;Wang S;Malter JS;Wang DS
淀粉样蛋白-β (a β)的大脑积聚是阿尔茨海默病（AD）发展的一致特征，也可能是其原因。除了生产失调外，越来越多的实验证据表明，分解代谢减少在Aβ积累中起着重要作用。虽然内皮素转换酶（ECE）和胰岛素降解酶（IDE）降解并因此有助于调节Aβ的稳态水平，但这些酶是如何调节的仍然知之甚少。在本研究中，我们研究了4-羟基壬烯醛（HNE）和Aβ对人神经母细胞瘤SH-SY5Y细胞中ECE-1和IDE表达和活性的影响。HNE或Aβ处理可上调ECE-1 mRNA和蛋白，而IDE未发生变化。虽然在HNE或Aβ处理24 h内ECE-1和IDE都被氧化，但ECE-1的催化活性升高，而IDE的比活性不变。结果首次证实了ECE-1和IDE都是Aβ诱导HNE修饰的底物。此外，结果表明复杂的机制调控其酶活性。
The cerebral accumulation of amyloid-β (Aβ) is a consistent feature of and likely contributor to the development of Alzheimer’s disease (AD). In addition to dysregulated production, increasing experimental evidence suggests reduced catabolism plays an important role in Aβ accumulation. Although endothelin converting enzyme (ECE) and insulin degrading enzyme (IDE) degrade and thus contribute to regulating the steady-state levels of Aβ, how these enzymes are regulated remain poorly understood. In this study, we investigated the effects of 4-hydroxy-nonenal (HNE) and Aβ on the expression and activity of ECE-1 and IDE in human neuroblastoma SH-SY5Y cells. Treatment with HNE or Aβ upregulated ECE-1 mRNA and protein, while IDE was unchanged. Although both ECE-1 and IDE were oxidized within 24 h of HNE or Aβ treatment, ECE-1 catalytic activity was elevated while IDE specific activity was unchanged. The results demonstrated for the first time that both ECE-1 and IDE are substrates of HNE modification induced by Aβ. In addition, the results suggest complex mechanisms underlying the regulation of their enzymatic activity.