Chen Changyou, Chen Haitao, Wang Pingping, Wang Xue, Wang Xuting, Chen Chuanfang, Pan Weidong
Beijing Key Laboratory of Bioelectromagnetism, Institute of Electrical Engineering, Chinese Academy of Sciences, Beijing 100190, China.
France-China International Laboratory of Evolution and Development of Magnetotactic Multicellular Organisms, Beijing 100190, China.
ACS Chem Biol. 2024 May 17;19(5):1151-1160. doi: 10.1021/acschembio.4c00090. Epub 2024 Apr 22.
Magnetogenetics has shown great potential for cell function and neuromodulation using heat or force effects under different magnetic fields; however, there is still a contradiction between experimental effects and underlying mechanisms by theoretical computation. In this study, we aimed to investigate the role of reactive oxygen species (ROS) in mechanical force-dependent regulation from a physicochemical perspective. The transient receptor potential vanilloid 4 (TRPV4) cation channels fused to ferritin (T4F) were overexpressed in HEK293T cells and exposed to static magnetic fields (sMF, 1.4-5.0 mT; gradient: 1.62 mT/cm). An elevation of ROS levels was found under sMF in T4F-overexpressing cells, which could lead to lipid oxidation. Compared with the overexpression of TRPV4, ferritin in T4F promoted the generation of ROS under the stimulation of sMF, probably related to the release of iron ions from ferritin. Then, the resulting ROS regulated the opening of the TRPV4 channel, which was attenuated by the direct addition of ROS inhibitors or an iron ion chelator, highlighting a close relationship among iron release, ROS production, and TRPV4 channel activation. Taken together, these findings indicate that the produced ROS under sMF act on the TRPV4 channel, regulating the influx of calcium ions. The study would provide a scientific basis for the application of magnetic regulation in cellular or neural regulation and disease treatment and contribute to the development of the more sensitive regulatory technology.
磁遗传学已显示出在不同磁场下利用热或力效应来调控细胞功能和神经调节方面的巨大潜力；然而，实验效应与理论计算的潜在机制之间仍存在矛盾。在本研究中，我们旨在从物理化学角度研究活性氧（ROS）在机械力依赖性调节中的作用。与铁蛋白融合的瞬时受体电位香草酸亚型4（TRPV4）阳离子通道（T4F）在HEK293T细胞中过表达，并暴露于静磁场（sMF，1.4 - 5.0 mT；梯度：1.62 mT/cm）。在过表达T4F的细胞中，发现静磁场下ROS水平升高，这可能导致脂质氧化。与TRPV4过表达相比，T4F中的铁蛋白在静磁场刺激下促进了ROS的产生，这可能与铁离子从铁蛋白中的释放有关。然后，产生的ROS调节TRPV4通道的开放，直接添加ROS抑制剂或铁离子螯合剂可使其减弱，这突出了铁释放、ROS产生和TRPV4通道激活之间的密切关系。综上所述，这些发现表明静磁场下产生的ROS作用于TRPV4通道，调节钙离子内流。该研究将为磁调节在细胞或神经调节及疾病治疗中的应用提供科学依据，并有助于开发更灵敏的调节技术。
