Low-intensity electromagnetic fields induce human cryptochrome to modulate intracellular reactive oxygen species

Abstract

Exposure to man-made electromagnetic fields (EMFs), which increasingly pollute our environment, have consequences for human health about which there is continuing ignorance and debate. Whereas there is considerable ongoing concern about their harmful effects, magnetic fields are at the same time being applied as therapeutic tools in regenerative medicine, oncology, orthopedics, and neurology. This paradox cannot be resolved until the cellular mechanisms underlying such effects are identified. Here, we show by biochemical and imaging experiments that exposure of mammalian cells to weak pulsed electromagnetic fields (PEMFs) stimulates rapid accumulation of reactive oxygen species (ROS), a potentially toxic metabolite with multiple roles in stress response and cellular ageing. Following exposure to PEMF, cell growth is slowed, and ROS-responsive genes are induced. These effects require the presence of cryptochrome, a putative magnetosensor that synthesizes ROS. We conclude that modulation of intracellular ROS via cryptochromes represents a general response to weak EMFs, which can account for either therapeutic or pathological effects depending on exposure. Clinically, our findings provide a rationale to optimize low field magnetic stimulation for novel therapeutic applications while warning against the possibility of harmful synergistic effects with environmental agents that further increase intracellular ROS.

Author summary

Repetitive low-intensity magnetic stimulation has been used in the treatment of disease for over 50 years. Associated benefits have included alleviation of depression, memory loss, and symptoms of Parkinson disease, as well as accelerated bone and wound healing and the treatment of certain cancers, independently of surgery or drugs. However, the cellular mechanisms underlying these effects remain unclear. Here, we demonstrate that repetitive magnetic field exposure in human cells stimulates production of biological stress response chemicals known as reactive oxygen species (ROS). At moderate doses, we find that reactive oxygen actively stimulates cellular repair and stress response pathways, which might account for the observed therapeutic effects to repetitive magnetic stimulation. We further show that this response requires the function of a well-characterized, evolutionarily conserved flavoprotein receptor known as cryptochrome, which has been implicated in magnetic sensing in organisms ranging from plants to flies, including migratory birds. We conclude that exposure to weak magnetic fields induces the production of ROS in human cells and that this process requires the presence of the cryptochrome receptor.