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.

Effect of static magnetic field on DNA synthesis: The interplay between DNA chirality and magnetic field left‐right asymmetry

“…One of the long-standing unsolved problems in biology has been the search for mechanisms of interactions between MFs and living cells and organisms. Despite the fact that many intriguing mechanisms have been suggested, [1][2][3][4][5][6][7][8] a fundamental aspect of the interaction between MF and cell-inherent DNA chirality and MF left-right (LR) asymmetry-has not been yet explored. Living organisms consist of chiral molecules that can exist in two mirror-symmetric forms: right-handed or left-handed enantiomers.…”

Geomagnetic field absence reduces adult body weight of a migratory insect by disrupting feeding behavior and appetite regulation

“…Additionally, recent computational work suggests that [FAD˙−-HO 2˙] or [FADH˙-O 2˙− ] can be alternative radical pairs at the origin of magnetoreception in Crys (Mondal and Huix-Rotllant, 2019), and ROS levels have also been shown to be sensitive to the changes in magnetic field intensity (Sherrard et al, 2018;Van Huizen et al, 2019). Moreover, it is well documented that ROS are critical in the regulation of energy metabolism and food intake due to their versatile roles in mediating the expression of vertebrate NPY (homolog of invertebrate NPF), glucose levels (Drougard et al, 2015) as well as the AKH/AKHR pathway (Kodrik et al, 2015).…”

“…Body weight is closely related to energy homeostasis in animals, and migratory fuelling which is characterized by gaining body mass and increased food intake during migration has been shown to be affected by GMF information (intensity, direction, or both) (Fransson et al, 2001;Henshaw et al, 2009;Henshaw et al, 2008;Kullberg et al, 2007). Interestingly, recent studies showed field intensity-dependent changes in the production of reactive oxygen species (ROS) which are regarded as signaling molecules for appetite-related neurons (Drougard et al, 2015;Sherrard et al, 2018;Van Huizen et al, 2019). Moreover, magnetic responses of adipokinetic hormone (AKH)/ AKH receptor (AKHR) signaling, reported to be involved in appetite regulation (Gáliková et al, 2017;Lin et al, 2019), was also found in adult rice planthoppers .…”

Melatonin Levels and Low‐Frequency Magnetic Fields in Humans and Rats: New Insights From a Bayesian Logistic Regression

“…While this connection between MLT levels and ELF‐MF lacked a clear mechanism, it seems to be related to the visual system as rats with severed optical nerves no longer respond to ELF‐MF [Olcese et al, ]. The exact mechanism with magneto‐receptors in the retina is now a plausible scenario in light of recent developments in the study of magnetoreception from behavioral [Kirschvink and Kirschvink, ; Phillips and Borland, ; Ritz et al, ; Johnsen and Lohmann, ; Wiltschko et al, ; Gegear et al, ; Yoshii et al, ; Winklhofer et al, ; Wiltschko and Wiltschko, ; Malkemper et al, ; Bazalova et al, ; Wiltschko et al, ; Sherrard et al, ] and theoretical investigations [e.g., Ritz et al, ; Hore and Mouritsen, ] where the cryptochrome (CRY) proteins discovered in the 1990s [Ahmad and Cashmore, ; Ahmad, ; Chasmore et al, ; Ahmad et al, ; Chaves et al, ; Ahmad, ] would provide the radical pair mechanism postulated by Schulten et al [] and be the (light‐dependent) MF receptor [Liedvogel and Mouritsen, ; Ritz et al, ; Hore and Mouritsen, ; Michael et al, ]. CRY proteins are widely expressed in cones and amacrine cells of the retina [e.g., Foley et al, ; Wong et al, ] and are thought to be the prime MF receptors involved in avian compass.…”

“…Under this hypothesis, weak MFs in the micro‐tesla range disrupt the biorhythms, leading to disrupted MLT production rendering MLT as an effective marker to be used in relation to weak MFs. Moreover, it has been shown that pulsed MFs (PMF) can also stimulate a rapid accumulation of reactive oxygen species (ROS)—a metabolite implicated in stress response and cellular aging—but only in insect cells expressing CRY [Sherrard et al, ], leading Landler and Keays [] to postulate that carcinogenesis associated with power lines, PMF‐induced ROS generation, and animal magnetoreception share a common mechanism.…”