Taurine Depletion Decreases GRP78 Expression and Downregulates Perk-Dependent Activation of the Unfolded Protein Response.
Taurine Depletion Decreases GRP78 Expression and Downregulates Perk-Dependent Activation of the Unfolded Protein Response.
复制标题
牛磺酸消耗会降低 GRP78 表达并下调未折叠蛋白反应的 Perk 依赖性激活。
DOI：
10.1007/978-3-319-15126-7_46
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发表时间：
2015
影响因子：
--
通讯作者：
Schaffer S.
中科院分区：
文献类型：
--
作者：
Jong CJ;Ito T;Azuma J;Schaffer S.
内质网（ER）是蛋白质合成和折叠的主要场所，具有干扰正确折叠的氧化环境。因此，有效的细胞质量控制机制对于良好平衡的ER稳态至关重要。由GRP 78严格调节的未折叠蛋白质反应（UPR）被激活作为一种适应性机制，以对抗导致ER应激的未折叠或错误折叠蛋白质的积累。在UPR的三条信号通路中，PERK-eIF 2 α-ATF 4通路诱导与抗氧化应激反应和凋亡相关的翻译基因。在目前的研究中，我们发现，牛磺酸耗竭，这已被报道导致线粒体氧化应激，降低GRP 78水平和下调PERK-eIF 2 α-ATF 4途径。这种下降可能与关键ER分子伴侣的氧化损伤有关。由于这种现象已在老年组织中观察到，我们的数据也表明，牛磺酸缺乏加速衰老过程。
The endoplasmic reticulum (ER) is the main site for protein synthesis and folding, with an oxidizing environment that interferes with proper folding. Therefore, an efficient cellular quality control mechanism is essential for well-balanced ER homeostasis. The Unfolded Protein Response (UPR), which is tightly regulated by GRP78, is activated as an adaptive mechanism against accumulation of unfolded or misfolded proteins that cause ER stress. Among the three signaling pathways of the UPR, the PERK-eIF2α-ATF4 pathway induces the translational genes associated with anti-oxidative stress responses and apoptosis. In the present study, we found that taurine depletion, which has been reported to cause mitochondrial oxidative stress, decreases GRP78 levels and downregulates the PERK-eIF2α-ATF4 pathway. This decline may be associated with oxidative damage to key ER chaperones. As this phenomenon has been observed in aged tissues, our data also suggest that taurine deficiency accelerates the aging process.