Association of DJ-1 with chaperones and enhanced association and colocalization with mitochondrial Hsp70 by oxidative stress
Association of DJ-1 with chaperones and enhanced association and colocalization with mitochondrial Hsp70 by oxidative stress
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DOI：
10.1080/10715760500260348
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发表时间：
2005-10-01
影响因子：
3.3
通讯作者：
Ariga, H
中科院分区：
文献类型：
--
作者：
Li, HM;Niki, T;Ariga, H
DF-1是一个新的癌基因，也是家族性帕金森病(PD)的致病基因。DJ-1已被证明通过消除活性氧物种(ROS)在抗氧化应激中发挥作用。帕金森病的发病被认为是由氧化应激和线粒体损伤引起的，线粒体损伤导致蛋白质聚集，导致神经细胞死亡。然而，DJ-1触发帕金森病发病的机制尚不清楚。在本研究中，我们分析了DJ-1及其突变体与各种伴侣蛋白的关联和定位。结果表明，DJ-1及其突变体与Hsp70、ChIP和线粒体驻留的Hsp70/Grp75相关；与野生型和其他DJ-1突变体相比，PD患者中发现的L166P和M26I突变与Hsp70和ChIP密切相关。DJ-1及其突变体与Hsp70和CHIP共定位于细胞内。此外，用过氧化氢处理细胞后，线粒体中野生型DJ-1与mtHsp70的结合和共存被增强。这些结果表明，氧化应激后DJ-1到线粒体的易位与伴侣蛋白有关。
Df-1 is a novel oncogene and causative gene for familial form of the Parkinson's disease (PD). DJ-1 has been shown to play a role in anti-oxidative stress by eliminating reactive oxygen species (ROS). The onset of PD is thought to be caused by oxidative stress and mitochondrial injury, which leads to protein aggregation that results in neuronal cell death. However, the mechanism by which DJ-1 triggers the onset of PD is still not clear. In this study, we analyzed association and localization of DJ-1 and its mutants with various chaperones. The results showed that DJ-1 and its mutants were associated with Hsp70, CHIP and mtHsp70/Grp75, a mitochondria-resident Hsp70, and that L166P and M26I mutants found in PD patients were strongly associated with Hsp70 and CHIP compared to wild-type and other DJ-1 mutants. DJ-1 and its mutants were colocalized with Hsp70 and CHIP in cells. Furthermore, association and colocalization of wildtype DJ-1 with mtHsp70 in mitochondria were found to be enhanced by treatment of cells with H2O2. These results suggest that translocation of DJ-1 to mitochondria after oxidative stress is carried out in association with chaperones.