Depletion of oxidative and endoplasmic reticulum stress regulators in Pick disease.
Depletion of oxidative and endoplasmic reticulum stress regulators in Pick disease.
复制标题
皮克病中氧化和内质网应激调节因子的耗竭。
DOI：
10.1016/j.freeradbiomed.2010.02.006
复制
发表时间：
2010
影响因子：
7.4
通讯作者：
M. Portero
中科院分区：
文献类型：
--
作者：
E. Ilieva;A. Naudí;Anton Kichev;I. Ferrer;R. Pamplona;M. Portero
氧化和内质网（ER）应激与多种神经退行性疾病，年龄相关性疾病。罕见的皮克病（PiD）与其他可能与氧化应激有关的神经退行性疾病有一些共同的病理特征。重要的是，激活的ER应激反应，这也是参与衰老，尚未在PiD研究。在这项研究中，我们评估了与氧化应激相关的ER应激在PiD中作为参与其发病机制的潜在机制的意义。从形态学上受影响的额叶皮质和明显病理保存枕叶皮质的样品显示不同蛋白质氧化损伤途径的区域依赖性增加。氧化修饰靶向抗氧化酶、蛋白酶、热休克蛋白和突触蛋白。这些影响与额叶皮质样本中蛋白酶体功能受损和ER应激有关。此外，我们还观察到ER伴侣（葡萄糖调节蛋白Grp 78/BiP和葡萄糖调节蛋白94）的耗竭以及未折叠蛋白反应期间细胞存活所需的核因子-红细胞2 p45相关呼吸2的组织含量和分布差异。这些结果表明PiD中区域特异性蛋白氧化损伤增加，蛋白酶体改变和功能失调的ER应激反应。我们认为这是由Grp 78/BiP的完全和特异性耗尽引起的，有助于这种神经退行性疾病的病理生理学。
Both oxidative and endoplasmic reticulum (ER) stress is associated with multiple neurodegenerative, age-related diseases. The rare disorder Pick disease (PiD) shares some pathological hallmarks of other neurodegenerative diseases that may be related to oxidative stress. Importantly, activation of an ER stress response, which is also involved in aging, has not yet been investigated in PiD. In this study, we assessed the implication of ER stress associated with oxidative stress in PiD as a potential mechanism involved in its pathogenesis. Samples from morphologically affected frontal cortex and apparently pathologically preserved occipital cortex showed region-dependent increases in different protein oxidative damage pathways. The oxidative modifications targeted antioxidant enzymes, proteases, heat shock proteins, and synaptic proteins. These effects were associated with compromised proteasomal function and ER stress in frontal cortex samples. In addition, we observed a depletion in ER chaperones (glucose-regulated proteins Grp78/BiP and glucose-regulated protein 94) and differences in tissue content and distribution of nuclear factor-erythroid 2 p45-related respiratory 2, required for cell survival during the unfolded protein response. These results demonstrate increased region-specific protein oxidative damage in PiD, with proteasomal alteration and dysfunctional ER stress response. We suggest this was caused by complete and specific depletion of Grp78/BiP, contributing to the pathophysiology of this neurodegenerative disease.
影响因子：
4.1
作者：
Poppek, Diana;Keck, Susi;Grune, Tilman
通讯作者：
Grune, Tilman
影响因子：
16
作者：
Harding, HP;Zhang, YH;Ron, D
通讯作者：
Ron, D