Interference of gadolinium dechelated from MR contrast agents by calcium signaling in neuronal cells of GnRH
Interference of gadolinium dechelated from MR contrast agents by calcium signaling in neuronal cells of GnRH
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DOI：
10.1002/jcp.30000
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发表时间：
2020-08-01
影响因子：
5.6
通讯作者：
Kelestimur, Haluk
中科院分区：
文献类型：
--
作者：
Baykara, Murat;Ozcan, Mete;Kelestimur, Haluk
磁共振成像（MRI）中使用的造影剂（CA）是通过将金属钆（Gd）与有机配体分子螯合形成稳定的络合物而产生的。但是，Gd（3+）可能从CA中解离出来，从而对环境产生毒性。除毒性外，它还可能抑制细胞膜上的钙通道，这种作用可能对控制生物发育的细胞有害。本研究的目的是探讨从CAs脱螯合的Gd 3+对促性腺激素释放激素（GnRH）神经元细胞中钙信号的干扰，调节青春期和性发育。本研究使用小鼠GT 1 -7细胞系作为模型系统，并且基于Fura-2的钙成像用于检测由CA释放的Gd 3+的细胞外存在引起的细胞内钙转运的中断;当细胞在体外培养中通过暴露于褪黑激素刺激时，钆双胺和钆特酸葡甲胺的作用最小。因此其在标准MRI检查中的使用是优选的。钆双胺中的Gd 3+释放是显着的，并且变得非常令人担忧，因为它可能会影响一般神经元细胞的神经生理学，特别是促性腺激素的产生，即使在没有肾源性系统性纤维化的正常患者中也是如此。脱螯合Gd ~（3+）内流GnRH神经元引起的毒性对青春期发育和生殖功能有重要意义。
Contrast agents (CAs) used in magnetic resonance imaging (MRI) are produced by chelating the metal gadolinium (Gd) with organic ligand molecules to form stable complexes. But, Gd(3+)may dissociate from the CAs and subsequently might become toxic to its environment. Besides toxicity, it might inhibit calcium channels on cell membranes and this action could be detrimental to the cells governing biological development. The aim of this study was to investigate the interference of Gd3+ dechelated from the CAs by calcium signaling in the neuronal cells of gonadotropin-releasing hormone (GnRH), regulating puberty, and sexual development. The study used the mouse GT1-7 cell line as a model system, and Fura-2 based calcium imaging for detecting the interruption of intracellular calcium transport by the extracellular presence of Gd3+ as released from the CAs; gadodiamide and gadoterate meglumine, when the cells were stimulated in vitro culture by exposure to melatonin.The CA gadoterate meglumine interfered minimally with the calcium signaling, and thus its use is preferable in standard MRI exams. The release of Gd3+ from gadodiamide was significant and becomes of great concern as it may impact the neurophysiology of the neuronal cells in general, and gonadotropin production in particular, even in normal patients without nephrogenic systemic fibrosis. The toxicity induced by the influx of dechelated Gd3+ in the neurons of GnRH would have significant implications for puberty and reproductive functions.