Gadolinium triggers unfolded protein responses (UPRs) in primary cultured rat cortical astrocytes via promotion of an influx of extracellular Ca2+
Gadolinium triggers unfolded protein responses (UPRs) in primary cultured rat cortical astrocytes via promotion of an influx of extracellular Ca2+
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钆通过促进细胞外 Ca2+ 的流入，触发原代培养的大鼠皮质星形胶质细胞中的未折叠蛋白反应 (UPR)
DOI：
10.1007/s10565-010-9166-2
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发表时间：
2011-02-01
影响因子：
6.1
通讯作者：
Wang, Kui
中科院分区：
文献类型：
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作者：
Feng, Xu-Dong;Xia, Qing;Wang, Kui
钆（Gd）及其配合物在工业和临床诊断中有着广泛的应用。作为一种稀土金属离子，游离钆（Gd 3+）在人体内的释放和滞留过程中存在神经毒性风险。在中枢神经系统中，星形胶质细胞在处理有毒金属离子方面发挥着关键作用。本研究评估了Gd对细胞钙稳态的影响，这是一种导致细胞死亡的常见机制，并对未折叠蛋白反应（UPRs）的影响，这是一种在哺乳动物细胞中对毒性刺激作出反应的细胞存活机制。实验结果表明，星形胶质细胞暴露于Gd后，细胞外Ca 2+内流大大增加，但没有观察到细胞死亡。进一步的证据表明，内质网（ER）驻留伴侣蛋白GRP78的表达上调ER应激介导的信号转导，特别是激活ATF 6，eIF2a，和IRE1。这些结果表明，Gd促进Ca 2+内流，从而触发UPR，这可能与星形胶质细胞对Gd诱导的细胞毒性的抵抗密切相关。
Gadolinium (Gd) and its complexes are utilized widely in industrial and clinical diagnoses. As a rare earth metal ion, free gadolinium (Gd3+) in the human body poses neurotoxic risks during its in vivo release and retention. In the central nervous system, astrocytes play a pivotal role in processing toxic metal ions. The present study evaluates the effects of Gd on cellular calcium homeostasis, a common mechanism that causes cell death, and on unfolded protein responses (UPRs), a mechanism for cell survival in response to toxic stimuli in mammalian cells. The experimental results indicate that the influx of extracellular Ca2+increases greatly after the exposure of astrocytes to Gd; however, no cell deaths were observed. Further evidence suggests the up-regulated expression of the endoplasmic reticulum (ER)-resident chaperone protein GRP78 by ER stress-mediated signal transductions, specifically the activation of ATF6, eIF2a, and IRE1. These results suggest that Gd promotes Ca2+influx, thus triggering UPRs, which can be closely associated to the resistance of astrocytes to Gd-induced cytotoxicity.