ENEA, Division of Health Protection Technologies, via Anguillarese 301, 00123 Rome, Italy.
Department of Information Engineering, Electronic, and Telecommunications, Sapienza University, 00184 Rome, Italy.
Biochim Biophys Acta Biomembr. 2019 Aug 1;1861(8):1446-1457. doi: 10.1016/j.bbamem.2019.06.005. Epub 2019 Jun 11.
Molecular mechanisms of interaction between cells and extremely low frequency magnetic fields (ELF-MFs) still represent a matter of scientific debate. In this paper, to identify the possible primary source of oxidative stress induced by ELF-MF in SH-SY5Y human neuroblastoma cells, we estimated the induced electric field and current density at the cell level.
We followed a computational multiscale approach, estimating the local electric field and current density from the whole sample down to the single cell level. The procedure takes into account morphological modeling of SH-SY5Y cells, arranged in different topologies. Experimental validation has been carried out: neuroblastoma cells have been treated with Diphenyleneiodonium (DPI) -an inhibitor of the plasma membrane enzyme NADPH oxidase (Nox)- administered 24 h before exposure to 50 Hz (1 mT) MF.
Macroscopic and microscopic dosimetric evaluations suggest that increased current densities are induced at the plasma membrane/extra-cellular medium interface; identifying the plasma membrane as the main site of the ELF-neuroblastoma cell interaction. The in vitro results provide an experimental proof that plasma membrane Nox exerts a key role in the redox imbalance elicited by ELF, as DPI treatment reverts the generation of reactive oxygen species induced by ELF exposure.
Microscopic current densities induced at the plasma membrane are likely to play an active physical role in eliciting ELF effects related to redox imbalance. Multiscale computational dosimetry, supported by an in vitro approach for validation, is proposed as the innovative and rigorous paradigm to unveil mechanisms underlying the complex ELF-MF interactions.
细胞与极低频磁场（ELF-MF）相互作用的分子机制仍然是科学争论的焦点。在本文中，为了确定 ELF-MF 在 SH-SY5Y 人神经母细胞瘤细胞中诱导氧化应激的可能主要来源，我们估计了细胞水平的感应电场和电流密度。
我们采用了一种计算多尺度方法，从整个样本到单细胞水平估计局部电场和电流密度。该过程考虑了 SH-SY5Y 细胞的形态建模，这些细胞以不同的拓扑结构排列。已经进行了实验验证：在暴露于 50Hz（1mT）MF 之前 24 小时，用二苯基碘鎓（DPI）-一种质膜酶 NADPH 氧化酶（Nox）的抑制剂处理神经母细胞瘤细胞。
宏观和微观剂量评估表明，在质膜/细胞外介质界面处诱导了更高的电流密度；确定质膜是 ELF-神经母细胞瘤细胞相互作用的主要部位。体外结果提供了实验证据，表明质膜 Nox 在 ELF 引起的氧化还原失衡中发挥关键作用，因为 DPI 处理可逆转 ELF 暴露引起的活性氧的产生。
质膜诱导的微观电流密度可能在引发与氧化还原失衡相关的 ELF 效应中发挥主动物理作用。多尺度计算剂量学，辅以体外验证方法，被提议作为揭示 ELF-MF 相互作用背后复杂机制的创新和严格范例。
