Expression profiles of genes in DJ-1-knockdown and L166P DJ-1 mutant cells
Expression profiles of genes in DJ-1-knockdown and L166P DJ-1 mutant cells
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DOI：
10.1016/j.neulet.2005.07.053
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发表时间：
2005-12-16
影响因子：
2.5
通讯作者：
Ariga, H
中科院分区：
文献类型：
--
作者：
Nishinaga, H;Takahashi-Niki, K;Ariga, H
DJ-1是一种新的致癌基因，也是家族性帕金森病（PD）的致病基因。DJ-1已被证明在抗氧化应激中发挥作用，通过消除活性氧和基因转录调节。DJ-1这些功能的丧失被认为是PD发病的诱因。在本研究中，为了鉴定受DJ-1表达调控的基因，我们对两种小鼠NIH3T3细胞系、DJ-1敲低细胞和PD患者中外源性添加L166P DJ-1突变体的细胞进行了DNA微阵列分析。在这两种细胞系中，观察到与应激、凋亡、氧化应激和神经毒性相关的基因表达发生了剧烈变化，并通过RT-PCR证实了表达的变化。在所鉴定的基因中，发现在dj -1敲除的细胞中，细胞外超氧化物歧化酶（SOD3）基因的表达水平降低，而SOD1和SOD2基因的表达没有变化。此外，在L166P DJ-1细胞中，tau基因的表达在启动子水平上增加，该基因的产物通过聚集使细胞具有神经毒性。这些发现表明，DJ-1调节的基因表达，其功能被认为与细胞死亡或神经退行性变有关。2005爱思唯尔爱尔兰有限公司版权所有。
DJ-1 is a novel oncogene and a causative gene for the familial form of Parkinson's disease (PD). DJ-1 has been shown to play roles in anti-oxidative stress by eliminating reactive oxygen species and in transcriptional regulation of genes. Loss of these functions of DJ-1 is thought to trigger the onset of PD. In this study, to identify genes for which expressions are regulated by DJ-1, DNA microarray analyses were carried out using two mouse NIH3T3 cell lines, DJ-1-knockdown cells and cells harboring an exogenously added L166P DJ-1 mutant found in PD patients. In both cell lines, drastic changes in expressions of genes, including genes related to stress, apoptosis, oxidative stress and neurotoxicity, were observed and changes in expressions were confirmed by RT-PCR. Of the genes identified, expression level of the extracellular superoxide dismutase (SOD3) gene was found to decrease in DJ-1-knockdown cells, while expressions of SOD1 and SOD2 genes did not change. Furthermore, expression of the tau gene, a gene whose product gives cells neurotoxicity by aggregation, was found to increase at its promoter level in L166P DJ-1 cells. These findings suggest that DJ-1 regulates expressions of genes for which functions are thought to be related to cell death or neurodegeneration. (C) 2005 Elsevier Ireland Ltd. All rights reserved.