Quinone-induced protein handling changes: implications for major protein handling systems in quinone-mediated toxicity.
Quinone-induced protein handling changes: implications for major protein handling systems in quinone-mediated toxicity.
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奎因酮诱导的蛋白质处理变化：对喹酮介导的毒性中主要蛋白质处理系统的影响。
DOI：
10.1016/j.taap.2014.08.014
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发表时间：
2014-10-15
影响因子：
3.8
通讯作者：
Ross, David
中科院分区：
文献类型：
--
作者：
Xiong, Rui;Siegel, David;Ross, David
对苯醌类化合物如1，4-苯醌（BQ）和甲萘醌（MD）以及邻醌类化合物包括儿茶酚胺的氧化产物，它们来源于外源性物质以及内源性分子。醌类对细胞中主要蛋白质处理系统的影响; 20/26 S蛋白酶体、ER应激反应、自噬、伴侣蛋白和攻击体形成，尚未以系统的方式进行研究。BQ和氨基色素（AC）均能抑制多巴胺能N27细胞蛋白酶体活性，激活内质网应激反应和自噬。AC还诱导侵略形成，而MD对N27细胞中的任何蛋白质处理系统几乎没有影响。使用NQO 1稳定转染的N27细胞检测NQO 1对醌诱导的蛋白质处理变化和毒性的影响，以产生等基因NQO 1过表达系。NQO 1保护对BK诱导的细胞凋亡，但导致AC和MD诱导的细胞凋亡的增强。在N27和NQO 1过表达细胞中，醌诱导的细胞凋亡的调节仅与ER应激反应的变化相关，而与其他蛋白处理系统的变化无关。这些数据表明，NQO 1调节ER应激反应，以增强AC和MD的毒性，但保护免受BQ毒性。我们进一步证明了NQO 1介导的还原为不稳定的氢醌和随后的氧化还原循环对于激活AC和MD的ER应激反应和毒性是重要的。总之，我们的数据表明，醌特异性的蛋白质处理的变化是明显的N27细胞和ER应激反应的诱导与醌介导的毒性。
Para-quinones such as 1,4-benzoquinone (BQ) and menadione (MD) and ortho-quinones including the oxidation products of catecholamines, are derived from xenobiotics as well as endogenous molecules. The effects of quinones on major protein handling systems in cells; the 20/26S proteasome, the ER stress response, autophagy, chaperone proteins and aggresome formation, have not been investigated in a systematic manner. Both BQ and aminochrome (AC) inhibited proteasomal activity and activated the ER stress response and autophagy in rat dopaminergic N27 cells. AC also induced aggresome formation while MD had little effect on any protein handling systems in N27 cells. The effect of NQO1 on quinone induced protein handling changes and toxicity was examined using N27 cells stably transfected with NQO1 to generate an isogenic NQO1-overexpressing line. NQO1 protected against BQ–induced apoptosis but led to a potentiation of AC- and MD-induced apoptosis. Modulation of quinone-induced apoptosis in N27 and NQO1-overexpressing cells correlated only with changes in the ER stress response and not with changes in other protein handling systems. These data suggested that NQO1 modulated the ER stress response to potentiate toxicity of AC and MD, but protected against BQ toxicity. We further demonstrated that NQO1 mediated reduction to unstable hydroquinones and subsequent redox cycling was important for the activation of the ER stress response and toxicity for both AC and MD. In summary, our data demonstrate that quinone-specific changes in protein handling are evident in N27 cells and the induction of the ER stress response is associated with quinone-mediated toxicity.
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影响因子：
4.1
作者：
LoPachin, Richard M.;Gavin, Terrence;Petersen, Dennis R.;Barber, David S.
通讯作者：
Barber, David S.
DOI：
10.1016/j.bbadis.2012.03.010
发表时间：
2012-07
影响因子：
6.2
作者：
Munoz, Patricia;Paris, Irmgard;Sanders, Laurie H.;Greenamyre, J. Timothy;Segura-Aguilar, Juan
通讯作者：
Segura-Aguilar, Juan
影响因子：
3.7
作者：
Paris, Irmgard;Perez-Pastene, Carolina;Segura-Aguilar, Juan
通讯作者：
Segura-Aguilar, Juan
影响因子：
56.9
作者：
Conway, KA;Rochet, JC;Lansbury, PT
通讯作者：
Lansbury, PT
DOI：
10.1073/pnas.77.9.5216
发表时间：
1980-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
BENSON, AM;HUNKELER, MJ;TALALAY, P
通讯作者：
TALALAY, P