Significant contribution of autophagy in mitigating cytotoxicity of gadolinium ions
Significant contribution of autophagy in mitigating cytotoxicity of gadolinium ions
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DOI：
10.1016/j.bbrc.2020.03.080
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发表时间：
2020-05-21
影响因子：
3.1
通讯作者：
Kiyono, Masako
中科院分区：
文献类型：
--
作者：
Takanezawa, Yasukazu;Nakamura, Ryosuke;Kiyono, Masako
钆基造影剂（GBCA）广泛应用于临床磁共振成像（MRI）。GBCA释放的游离钆离子（Gd 3+）可能会增加GBCA相关毒性的风险。然而，对Gd 3+的细胞反应和负责保护免受Gd 3+的潜在机制仍然知之甚少。最近，自噬被认为是细胞抵抗各种有毒金属的生存机制。在这里，我们研究了Gd 3+和自噬之间的关系，以及自噬抑制对暴露于Gd 3+的细胞存活的影响。我们发现，在接触Gd 3+的人胚肾293（HEK 293）细胞中，自噬标志蛋白--微管相关蛋白1轻链3（LC 3）-II的表达增加。此外，我们发现暴露于自噬抑制剂氯喹（CQ）与Gd 3+组合后的LC 3-II的积累比单独暴露于CQ后更大，表明Gd 3+激活HEK 293细胞中的自噬。此外，我们发现Gd 3+降低细胞活力，这在CQ处理后更明显。我们的研究结果表明，自噬对Gd 3+毒性产生细胞保护作用，表明自噬和GBCA相关不良事件之间存在潜在联系。(C)2020爱思唯尔公司All rights reserved.
Gadolinium-based contrast agents (GBCAs) are widely used in clinical magnetic resonance imaging (MRI). Free gadolinium ions (Gd3+) released from GBCAs potentially increase the risk of GBCA-related toxicity. However, the cellular responses to Gd3+ and the underlying mechanisms responsible for protection against Gd3+ remain poorly understood. Recently, autophagy has been considered a cell survival mechanism against various toxic metals. Here, we investigated the relationship between Gd3+ and autophagy, as well as the effect of autophagy inhibition on the survival of cells exposed to Gd3+. We found that the increased expression of microtubule-associated protein 1 light chain 3 (LC3)-II, a marker protein of autophagy, in Gd3+-exposed human embryonic kidney 293 (HEK293) cells. Moreover, we found a greater accumulation of LC3-II after exposure to an autophagy inhibitor, chloroquine (CQ), combined with Gd3+ than that after exposure to CQ alone, suggesting that Gd3+ activated autophagy in HEK293 cells. Furthermore, we found that Gd3+ reduced cell viability, which was more pronounced after CQ treatment. Our findings indicated that autophagy exerted a cytoprotective effect against Gd3+ toxicity, suggesting a potential link between autophagy and GBCA-associated adverse events. (C) 2020 Elsevier Inc. All rights reserved.