Franco-Obregón Alfredo
Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.
Institute of Health Technology and Innovation (iHealthtech), National University of Singapore, Singapore 117599, Singapore.
Bioengineering (Basel). 2023 Oct 10;10(10):1176. doi: 10.3390/bioengineering10101176.
Mitohormesis is a process whereby mitochondrial stress responses, mediated by reactive oxygen species (ROS), act cumulatively to either instill survival adaptations (low ROS levels) or to produce cell damage (high ROS levels). The mitohormetic nature of extremely low-frequency electromagnetic field (ELF-EMF) exposure thus makes it susceptible to extraneous influences that also impinge on mitochondrial ROS production and contribute to the collective response. Consequently, magnetic stimulation paradigms are prone to experimental variability depending on diverse circumstances. The failure, or inability, to control for these factors has contributed to the existing discrepancies between published reports and in the interpretations made from the results generated therein. Confounding environmental factors include ambient magnetic fields, temperature, the mechanical environment, and the conventional use of aminoglycoside antibiotics. Biological factors include cell type and seeding density as well as the developmental, inflammatory, or senescence statuses of cells that depend on the prior handling of the experimental sample. Technological aspects include magnetic field directionality, uniformity, amplitude, and duration of exposure. All these factors will exhibit manifestations at the level of ROS production that will culminate as a unified cellular response in conjunction with magnetic exposure. Fortunately, many of these factors are under the control of the experimenter. This review will focus on delineating areas requiring technical and biological harmonization to assist in the designing of therapeutic strategies with more clearly defined and better predicted outcomes and to improve the mechanistic interpretation of the generated data, rather than on precise applications. This review will also explore the underlying mechanistic similarities between magnetic field exposure and other forms of biophysical stimuli, such as mechanical stimuli, that mutually induce elevations in intracellular calcium and ROS as a prerequisite for biological outcome. These forms of biophysical stimuli commonly invoke the activity of transient receptor potential cation channel classes, such as TRPC1.
线粒体应激反应是一个过程，在此过程中，由活性氧（ROS）介导的线粒体应激反应会累积作用，以产生生存适应性（低ROS水平）或导致细胞损伤（高ROS水平）。因此，极低频电磁场（ELF - EMF）暴露的线粒体应激效应使其容易受到其他也会影响线粒体ROS产生并促成集体反应的外部影响。因此，磁刺激模式容易因不同情况而出现实验变异性。未能控制这些因素导致了已发表报告之间以及从中得出的结果解释中存在现有差异。混杂的环境因素包括环境磁场、温度、机械环境以及氨基糖苷类抗生素的常规使用。生物学因素包括细胞类型、接种密度以及细胞的发育、炎症或衰老状态，这些取决于实验样本的先前处理情况。技术方面包括磁场的方向性、均匀性、幅度和暴露持续时间。所有这些因素都会在ROS产生水平上表现出来，并最终与磁暴露一起作为统一的细胞反应。幸运的是，其中许多因素都在实验者的控制之下。本综述将重点描述需要技术和生物学协调的领域，以协助设计具有更明确界定和更好预测结果的治疗策略，并改善对所生成数据的机制解释，而不是精确应用。本综述还将探讨磁场暴露与其他形式的生物物理刺激（如机械刺激）之间潜在的机制相似性，这些刺激相互诱导细胞内钙和ROS升高，作为生物学结果的先决条件。这些形式的生物物理刺激通常会激活瞬时受体电位阳离子通道类别的活性，如TRPC1。
