A mechanism underlies fish GRP78 protection against Pb2+toxicity
A mechanism underlies fish GRP78 protection against Pb2+toxicity
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鱼类 GRP78 抵御 Pb2 毒性的机制
DOI：
10.1016/j.fsi.2017.03.056
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发表时间：
2017
影响因子：
4.7
通讯作者：
Hu Chengyu
中科院分区：
文献类型：
--
作者：
Zhong Bin;Wang Xiangqin;Mao Huilin;Wan Yiqi;Liu Yi;Zhang Tao;Hu Chengyu
重金属暴露会影响基本的细胞过程并导致严重的毒理学效应。 Pb2+ 可以通过蛋白质变性、改变细胞内钙稳态和诱导细胞死亡来激活对内质网 (ER) 应激的反应。作为一种 ER 滞留蛋白，78 kDa 葡萄糖调节蛋白 (GRP78) 可以缓解 Pb2+ 诱导的 ER 应激并增强细胞活力。我们之前表明，Pb2+等重金属离子。以时间和剂量依赖性方式对鱼类细胞系有害。这一现象伴随着草鱼GRP78（CiGRP78）的不断积累，它可以保护细胞免受重金属离子的细胞毒性。在这里，我们研究了 CiGRP78 发挥其保护功能的机制。利用金属离子亲和洗脱法和荧光光谱分析，我们表明CiGRP78可以分别与钙、铅和镉离子形成络合物，特别是在体外与铅离子形成络合物。然而，另一种内质网滞留蛋白 CiGRP94 不能与 Pb2+ 结合，这凸显了 CiGRP78 和 CiGRP94 在调节重金属细胞毒性方面可能存在功能差异。我们的结果表明，CiGRP78 可能通过与 Pb2+ 的直接相互作用来增加细胞对 Pb2+ 的耐受性。
Heavy metal exposure impacts basic cellular processes and results in serious toxicological effects. Pb2+can activate the response to endoplasmic reticulum (ER) stress by protein denaturation, changing intracellular calcium homeostasis, and inducing cell death. As an ER retention protein, 78-kDa glucose-regulated protein (GRP78) can relieve the Pb2+-induced ER stress and enhance cell viability. We previously showed that heavy metal ions such as Pb2+etc. are harmful to fish cell lines in a time- and dose-dependent manner. The phenomenon is accompanied by the increasing accumulation of grass carp GRP78 (CiGRP78), which can protect the cells from heavy metal ion cytotoxicity. Here, we investigated the mechanism in which CiGRP78 exerted its protective function. Using metal ions affinity elution method and fluorescent spectral analysis, we showed that CiGRP78 could respectively form a complex with Calcium, Lead and Cadmium ions, especially with Lead ionin vitro. However, another ER retention protein CiGRP94 could not bind to Pb2+, highlighting the functional differentiation might exist in CiGRP78 and CiGRP94 in regulating heavy metal cytotoxicity. Our results suggested that CiGRP78 might increase cellular tolerance to Pb2+via the direct interaction with it.