PI3K is a key molecule in the Nrf2-mediated regulation of antioxidative proteins by hemin in human neuroblastoma cells
PI3K is a key molecule in the Nrf2-mediated regulation of antioxidative proteins by hemin in human neuroblastoma cells
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DOI：
10.1016/s0014-5793(03)00517-9
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发表时间：
2003-07-10
期刊：
影响因子：
3.5
通讯作者：
Nakashima, K
中科院分区：
文献类型：
--
作者：
Nakaso, K;Yano, H;Nakashima, K
氧化应激和铁代谢在帕金森氏病的发病机制中起重要作用。在多巴胺能神经元中，几种应激蛋白在氧化应激下上调。为了阐明这一机制，我们在SH-SY5Y细胞中研究了氯化血红素相关的信号转导和氧化应激相关蛋白的诱导。我们发现磷脂酰肌醇3-激酶(PI3K)和Nrf2是诱导血红素加氧酶-1、硫氧还蛋白和过氧化还蛋白-I的重要分子。PI3K相关信号控制着Nrf2的激活，因此，PI3K抑制剂阻断了Nrf2的核转位和应激蛋白的诱导。这些观察结果表明，PI3K和Nrf2是在氧化应激和铁代谢下维持适当条件的关键分子。(C)2003年欧洲生化学会联合会。爱思唯尔科学公司出版。版权所有。
Oxidative stress and ferrous metabolism are important in the pathogenesis in Parkinson's disease. In dopaminergic neurons, several stress proteins are upregulated under oxidative stress. To clarify this mechanism, we investigated hemin-related signal transduction and the induction of oxidative stress-related proteins in SH-SY5Y cells. We identified phosphatidylinositol 3-kinase (PI3K) and Nrf2 as important molecules in the induction of heme oxygenase-1, thioredoxin, and peroxiredoxin-I. PI3K-related signal controlled Nrf2 activation, and consequently, PI3k inhibitors blocked the nuclear translocation of Nrf2 and induction of stress proteins. These observations suggest that PI3K and Nrf2 are key molecules in maintaining suitable conditions under oxidative stress and ferrous metabolism. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.