Endoplasmic Reticulum Stress and Oxidative Stress: A Vicious Nexus Implicated in Bowel Disease Pathophysiology.
Endoplasmic Reticulum Stress and Oxidative Stress: A Vicious Nexus Implicated in Bowel Disease Pathophysiology.
复制标题
内质网应激和氧化应激：与肠道疾病病理生理学有关的恶性联系。
DOI：
10.3390/ijms18040771
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发表时间：
2017-04-05
影响因子：
5.6
通讯作者：
Eri R
中科院分区：
文献类型：
--
作者：
Chong WC;Shastri MD;Eri R
内质网（ER）是一种复杂的蛋白质折叠和运输细胞器。内质网环境的改变和差异会影响蛋白质折叠过程，因此可能导致错误折叠蛋白质的产生。错误折叠蛋白质的积累会导致细胞损伤并引发内质网应激。在这种应激条件下，细胞表现出功能合成减少，如果应激时间延长，细胞就会发生凋亡。为了解决内质网应激，细胞触发一种称为未折叠蛋白反应（UPR）的内在机制。 UPR是一种适应性信号过程，通过内质网跨膜转导器触发多条通路，减少和去除错误折叠的蛋白质，改善蛋白质折叠机制，从而改善和维持内质网稳态。越来越多的研究支持氧化应激与内质网应激密切相关的观点。在蛋白质折叠过程中，会产生副产物活性氧，导致氧化还原平衡受损，从而产生氧化应激。由于蛋白质折叠过程依赖于氧化还原稳态，氧化应激会破坏蛋白质折叠机制并增加错误折叠蛋白质的产生，从而导致进一步的内质网应激。有人提出，内质网应激和氧化应激在肠道疾病的病理生理学中共同发挥重要作用。
The endoplasmic reticulum (ER) is a complex protein folding and trafficking organelle. Alteration and discrepancy in the endoplasmic reticulum environment can affect the protein folding process and hence, can result in the production of misfolded proteins. The accumulation of misfolded proteins causes cellular damage and elicits endoplasmic reticulum stress. Under such stress conditions, cells exhibit reduced functional synthesis, and will undergo apoptosis if the stress is prolonged. To resolve the ER stress, cells trigger an intrinsic mechanism called an unfolded protein response (UPR). UPR is an adaptive signaling process that triggers multiple pathways through the endoplasmic reticulum transmembrane transducers, to reduce and remove misfolded proteins and improve the protein folding mechanism, in order to improve and maintain endoplasmic reticulum homeostasis. An increasing number of studies support the view that oxidative stress has a strong connection with ER stress. During the protein folding process, reactive oxygen species are produced as by-products, leading to impaired reduction-oxidation (redox) balance conferring oxidative stress. As the protein folding process is dependent on redox homeostasis, the oxidative stress can disrupt the protein folding mechanism and enhance the production of misfolded proteins, causing further ER stress. It is proposed that endoplasmic reticulum stress and oxidative stress together play significant roles in the pathophysiology of bowel diseases.