Establishment of a system for monitoring endoplasmic reticulum redox state in mammalian cells.

Establishment of a system for monitoring endoplasmic reticulum redox state in mammalian cells.
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DOI:
10.1038/labinvest.2013.112
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发表时间:
2013-11
期刊:
Laboratory investigation; a journal of technical methods and pathology
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其他
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内质网(ER)在新生蛋白质的氧化折叠中起着至关重要的作用,内质网稳态的破坏可能导致蛋白质的错误折叠和随后的病理过程。在维持内质网稳态的机制中,氧化还原调节是决定内质网应激细胞命运的关键因素。在这里,我们报告了一个监测哺乳动物细胞内质网氧化还原状态的系统的建立。新的ER氧化还原传感系统是在之前描述的酵母氧化还原监测系统的基础上开发的。我们的系统可以成功地监测哺乳动物细胞中ER氧化还原的动态状态。利用该系统,我们发现操纵ER氧化酶改变了ER的氧化还原状态。哺乳动物ER氧化还原传感系统可用于研究ER氧化还原调节机制,为开发治疗糖尿病、神经退行性变和Wolfram综合征等与ER稳态失调相关的人类疾病的新方法提供基础。
The endoplasmic reticulum (ER) performs a critical role in the oxidative folding of nascent proteins such that perturbations to ER homeostasis may lead to protein misfolding and subsequent pathological processes. Among the mechanisms for maintaining ER homeostasis is a redox regulation, which is a critical determinant of the fate of ER stressed cells. Here we report the establishment of a system for monitoring ER redox state in mammalian cells. The new ER redox sensing system was developed based on the previously described monitoring system in yeast. Our system could successfully monitor the dynamic ER redox state in mammalian cells. Using this system, we find that manipulation of ER oxidases changes ER redox state. The mammalian ER redox sensing system could be used to study the mechanisms of ER redox regulation and provide a foundation for an approach to develop novel therapeutic modalities for human diseases related to dysregulated ER homeostasis including diabetes, neurodegeneration and Wolfram syndrome.
真核生物中的氧化蛋白折叠:机制和后果。
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