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Magnetic field-induced Ca2+ intake by mesenchymal stem cells is mediated by intracellular Zn2+ and accompanied by a Zn2+ influx
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research ( IF 4.6 ) Pub Date : 2021-05-24 , DOI: 10.1016/j.bbamcr.2021.119062
Alp Özgün 1 , Bora Garipcan 1
Affiliation  

Chronic exposure to magnetic fields (MFs) has a diverse range of effects on biological systems but definitive molecular mechanisms of the interaction remain largely unknown. One of the most frequently reported effects of MF exposure is an elevated concentration of intracellular Ca2+ through disputed pathways. Other prominent effects include increased oxidative stress and upregulation of neural markers through EGFR activation in stem cells. Further characterization of cascades triggered by MF exposure is hindered by the phenotype diversity of biological models used in the literature. In an attempt to reveal more mechanistic data in this field, we combined the most commonly used biological model and MF parameters with the most commonly reported effects of MFs.

Based on clues from the pathways previously defined as sensitive to MFs (EGFR and Zn2+-binding enzymes), the roles of different types of channels (voltage gated Ca2+ channels, NMDA receptors, TRP channels) were inquired in the effects of 50 Hz MFs on bone marrow-derived mesenchymal stem cells. We report that, an influx of Zn2+ accompanies MF-induced Ca2+ intake, which is only attenuated by the broad-range inhibitor of TRP channels and store-operated Ca2+ entry (SOCE), 2-Aminoethoxydiphenyl borate (2-APB) among other blockers (memantine, nifedipine, ethosuximide and gabapentin). Interestingly, cation influx completely disappears when intracellular Zn2+ is chelated. Our results rule out voltage gated Ca2+ channels as a gateway to MF-induced Ca2+ intake and suggest Zn2+-related channels as a new focus in the field.



中文翻译:

磁场诱导的间充质干细胞对 Ca2+ 的摄入是由细胞内 Zn2+ 介导的,并伴有 Zn2+ 流入

长期暴露于磁场 (MF) 对生物系统有多种影响,但相互作用的明确分子机制在很大程度上仍然未知。MF 暴露最常报道的影响之一是通过有争议的途径使细胞内 Ca 2+浓度升高。其他突出的影响包括通过干细胞中的 EGFR 激活增加氧化应激和神经标志物的上调。MF 暴露引发的级联的进一步表征受到文献中使用的生物模型的表型多样性的阻碍。为了揭示该领域更多的机械数据,我们将最常用的生物模型和 MF 参数与最常报告的 MF 效应相结合。

基于先前定义为对 MFs(EGFR 和 Zn 2+结合酶)敏感的途径的线索,不同类型的通道(电压门控 Ca 2+通道、NMDA 受体、TRP 通道)在骨髓间充质干细胞上的 50 Hz MF。我们报告说,锌2+的流入伴随着 MF 诱导的 Ca 2+摄入,这仅被 TRP 通道的广谱抑制剂和储存操作的 Ca 2+进入(SOCE)、2-氨基乙氧基二苯基硼酸盐(2 -APB) 以及其他阻滞剂(美金刚胺、硝苯地平、乙琥胺和加巴喷丁)。有趣的是,当细胞内 Zn 2+被螯合。我们的结果排除了电压门控 Ca 2+通道作为通向 MF 诱导的 Ca 2+摄入的途径,并建议将 Zn 2+相关通道作为该领域的新焦点。

更新日期:2021-05-30
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