Chaperone-independent mitochondrial translocation and protection by αB-crystallin in RPE cells.

Chaperone-independent mitochondrial translocation and protection by αB-crystallin in RPE cells.
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DOI:
10.1016/j.exer.2013.02.016
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发表时间:
2013-05
影响因子:
3.4
通讯作者:
Kantorow M
Kantorow M
中科院分区:
医学3区
文献类型:
--
作者:
McGreal RS;Brennan LA;Kantorow WL;Wilcox JD;Wei J;Chauss D;Kantorow M

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α B-晶状体蛋白是一种小分子热休克蛋白,具有分子伴侣活性,可以保护多种细胞类型免受氧化应激损伤。α B-晶状体蛋白水平的改变和特异性突变与多种退行性疾病相关。我们以前发现,α B-晶状体蛋白易位到透镜和视网膜细胞线粒体氧化应激暴露后,它提供了保护氧化应激损伤。迄今为止,α B-晶状体蛋白的伴侣蛋白功能在线粒体易位和保护中的作用尚未确定。在这里,我们试图确定α B-晶状体蛋白的伴侣活性与其移位到视网膜细胞线粒体并保护其免受氧化应激损伤的能力之间的关系。我们的数据提供证据表明,表现出不同伴侣活性水平的三种形式的α B-晶状体蛋白,包括野生型、R120 G(伴侣活性降低)和M68 A(伴侣活性增加),提供了相当水平的线粒体易位和对暴露于氧化应激的视网膜细胞的保护。结果表明,α B-晶状体蛋白的线粒体转位和保护作用与其分子伴侣活性无关,α B-晶状体蛋白的其他功能也可能与其分子伴侣活性无关。
αB-crystallin is a small heat shock protein that exhibits chaperone activity and can protect multiple cell types against oxidative stress damage. Altered levels and specific mutations of αB-crystallin are associated with multiple degenerative diseases. We previously found that αB-crystallin translocates to lens and retinal cell mitochondria upon oxidative stress exposure where it provides protection against oxidative stress damage. To date, the role of the chaperone function of αB-crystallin in mitochondrial translocation and protection has not been established. Here, we sought to determine the relationship between the chaperone activity of αB-crystallin and its ability to translocate to and protect retinal cell mitochondria against oxidative stress damage. Our data provide evidence that three forms of αB-crystallin exhibiting different chaperone activity levels including wild-type, R120G (decreased chaperone activity) and M68A (increased chaperone activity) provide comparable levels of mitochondrial translocation and protection to retinal cells exposed to oxidative stress. The results provide evidence that mitochondrial translocation and protection by αB-crystallin is independent of its chaperone activity and that other functions of αB-crystallin may also be independent of its chaperone activity.
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