Ultraviolet A Induces Endoplasmic Reticulum Stress Response in Human Dermal Fibroblasts
Ultraviolet A Induces Endoplasmic Reticulum Stress Response in Human Dermal Fibroblasts
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DOI：
10.1247/csf.11041
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发表时间：
2012-01-01
影响因子：
1.5
通讯作者：
Yoshida, Hiderou
中科院分区：
文献类型：
--
作者：
Komori, Ryota;Taniguchi, Mai;Yoshida, Hiderou
内质网（ER）应激反应是哺乳动物内质网（ER）应激中未折叠蛋白积累的细胞保护机制，由三种反应途径（ATF6、IRE1和PERK途径）组成。这些通路分别通过特定的顺式作用元件ERSE、uppe和AARE调控er相关基因的转录。由于哺乳动物内质网应激反应在专业分泌细胞中被显著激活，其主要功能被认为是上调内质网中蛋白质折叠的能力，以配合分泌蛋白合成的增加。在这里，我们发现紫外线A （UVA）照射诱导内质网定位的传感器pATF6 α (P)在正常人真皮成纤维细胞（nffs）中转化为活性转录因子pATF6 α (N)。UVA还诱导ire1介导的XBP1 mRNA剪接以及perk介导的真核起始因子2的a亚基磷酸化。与这些观察结果一致，我们发现UVA增加了ERSE， upe和AARE元件的转录。根据这些结果，我们得出结论，UVA照射激活了ndfs中哺乳动物内质网应激反应的所有分支。这表明哺乳动物内质网应激反应不仅受到内在应激的激活，还受到环境应激的激活。
The endoplasmic reticulum (ER) stress response is a cytoprotective mechanism against the accumulation of unfolded proteins in the ER (ER stress) that consists of three response pathways (the ATF6, IRE1 and PERK pathways) in mammals. These pathways regulate the transcription of ER-related genes through specific cis-acting elements, ERSE, UPRE and AARE, respectively. Because the mammalian ER stress response is markedly activated in professional secretory cells, its main function was thought to be to upregulate the capacity of protein folding in the ER in accordance with the increased synthesis of secretory proteins. Here, we found that ultraviolet A (UVA) irradiation induced the conversion of an ER-localized sensor pATF6 alpha(P) to an active transcription factor pATF6 alpha(N) in normal human dermal fibroblasts (NHDFs). UVA also induced IRE1-mediated splicing of XBP1 mRNA as well as PERK-mediated phosphorylation of an a subunit of eukaryotic initiation factor 2. Consistent with these observations, we found that UVA increased transcription from ERSE, UPRE and AARE elements. From these results, we concluded that UVA irradiation activates all branches of the mammalian ER stress response in NHDFs. This suggests that the mammalian ER stress response is activated by not only intrinsic stress but also environmental stress.