Role of the unfolded protein response (UPR) in cataract formation
Role of the unfolded protein response (UPR) in cataract formation
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DOI：
10.1016/j.exer.2006.01.033
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发表时间：
2006-09-01
影响因子：
3.4
通讯作者：
Shinohara, Toshimichi
中科院分区：
文献类型：
--
作者：
Ikesugi, Kengo;Yamamoto, Ryoko;Shinohara, Toshimichi
白内障是一种多因素疾病，各种各样的应激因素诱发白内障。许多致白内障应激源和内质网（ER）应激源诱导各种细胞类型的未折叠蛋白反应（UPR）。已知UPR在诱导细胞凋亡之前产生活性氧（ROS）。我们研究了内质网应激是否诱导透镜上皮细胞（LECs）或整个大鼠晶状体中的UPR。我们的研究结果表明，更高水平的ER应激激活Bip/GRP 78，ATF 4和caspase-12。此外，ROS产生，游离谷胱甘肽减少，并诱导细胞凋亡。有丝分裂区的LEC对UPR最敏感，而中心LEC最耐药。UPR诱导ER和线粒体产生ROS。培养晶状体中可检测到的ROS产生仅限于上皮细胞。这些结果表明，ER应激诱导的UPR在LECs的诱导和不诱导凋亡，我们的结论是，UPR可能是许多类型的白内障的起始因素之一。(c)2006爱思唯尔有限公司保留所有权利。
Cataract is a multifactorial disease, and a large variety of stressors induce cataracts. Many cataractogenic stressors and endoplasmic reticulum (ER) stressors induce the unfolded protein response (UPR) in various cell types. The UPR is known to produce reactive oxygen species (ROS) prior to the inducement of apoptosis. We investigated whether ER stressors induce the UPR in lens epithelial cells (LECs) or whole rat lenses. Our results showed that higher levels of ER stressors activated Bip/GRP78, ATF4, and caspase-12. In addition, ROS were produced, free glutathione was decreased, and apoptosis was induced. LECs in the mitotic zone were the most susceptible to the UPR while the central LECs were the most resistant. The UPR induced the production of ROS in the ER and probably in the mitochondria. The detectable ROS production in cultured lenses is limited to the epithelial cells. These findings indicate that ER stressors induce the UPR in LECs with and without the induction of apoptosis, and we conclude that the UPR is probably one of the initiating factors of many types of cataracts. (c) 2006 Elsevier Ltd. All rights reserved.