ER stress protects from retinal degeneration
ER stress protects from retinal degeneration
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DOI：
10.1038/emboj.2009.76
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发表时间：
2009-05-06
期刊：
影响因子：
11.4
通讯作者：
Mollereau, Bertrand
中科院分区：
文献类型：
--
作者：
Mendes, Cesar S.;Levet, Clemence;Mollereau, Bertrand
未折叠蛋白反应（UPR）是一种特殊的细胞过程，它允许细胞应对内质网（ER）中未折叠/错误折叠蛋白的过载。内质网应激通常与退行性病理有关，但其在疾病进展中的作用仍有争议。在这里，我们发现内质网驻留伴侣的突变，既不是失活也不是后电位A (NinaA)，导致轻度内质网应激，保护成年果蝇的光感受器神经元免受各种死亡刺激。此外，当预先暴露于轻度内质网应激时，果蝇S2培养的细胞可以免受H(2)O(2)、环己亚胺或紫外线诱导的细胞死亡。我们表明，特定的er介导的信号促进抗氧化防御和抑制caspase依赖性细胞死亡。我们认为普遍定期审议的直接结果不仅限制了错误折叠蛋白质的积累，而且保护组织免受有害的外源应激。生物医学工程学报（2009）28,1296-1307。doi: 10.1038 / emboj.2009.76;2009年4月2日在线发布
The unfolded protein response (UPR) is a specific cellular process that allows the cell to cope with the overload of unfolded/misfolded proteins in the endoplasmic reticulum (ER). ER stress is commonly associated with degenerative pathologies, but its role in disease progression is still a matter for debate. Here, we found that mutations in the ER-resident chaperone, neither inactivation nor afterpotential A (NinaA), lead to mild ER stress, protecting photoreceptor neurons from various death stimuli in adult Drosophila. In addition, Drosophila S2 cultured cells, when pre-exposed to mild ER stress, are protected from H(2)O(2), cycloheximide-or ultraviolet-induced cell death. We show that a specific ER-mediated signal promotes antioxidant defences and inhibits caspase-dependent cell death. We propose that an immediate consequence of the UPR not only limits the accumulation of misfolded proteins but also protects tissues from harmful exogenous stresses. The EMBO Journal (2009) 28, 1296-1307. doi: 10.1038/emboj.2009.76; Published online 2 April 2009