Moderate strength (0.23–0.28 T) static magnetic fields (SMF) modulate signaling and differentiation in human embryonic cells

Abstract

BackgroundCompelling evidence exists that magnetic fields modulate living systems. To date, however, rigorous studies have focused on identifying the molecular-level biosensor (e.g., radical ion pairs or membranes) or on the behavior of whole animals leaving a gap in understanding how molecular effects are translated into tissue-wide and organism-level responses. This study begins to bridge this gulf by investigating static magnetic fields (SMF) through global mRNA profiling in human embryonic cells coupled with software analysis to identify the affected signaling pathways.ResultsSoftware analysis of gene expression in cells exposed to 0.23–0.28 T SMF showed that nine signaling networks responded to SMF; of these, detailed biochemical validation was performed for the network linked to the inflammatory cytokine IL-6. We found the short-term (<24 h) activation of IL-6 involved the coordinate up-regulation of toll-like receptor-4 (TLR4) with complementary changes to NEU3 and ST3GAL5 that reduced ganglioside GM3 in a manner that augmented the activation of TLR4 and IL-6. Loss of GM3 also provided a plausible mechanism for the attenuation of cellular responses to SMF that occurred over longer exposure periods. Finally, SMF-mediated responses were manifest at the cellular level as morphological changes and biochemical markers indicative of pre-oligodendrocyte differentiation.ConclusionThis study provides a framework describing how magnetic exposure is transduced from a plausible molecular biosensor (lipid membranes) to cell-level responses that include differentiation toward neural lineages. In addition, SMF provided a stimulus that uncovered new relationships – that exist even in the absence of magnetic fields – between gangliosides, the time-dependent regulation of IL-6 signaling by these glycosphingolipids, and the fate of embryonic cells.

Involvement of Na+/K+pump in fine modulation of bursting activity of the snail Br neuron by 10 mT static magnetic field

“…pump is regulated by protein phosphatases (PPases) and protein kinases A and G (PKA and PKG) (Therien and Blostein 2000;Ramnanan and Storey 2006). SMF-induced changes from literature are up-and downregulation of genes involved in cellular metabolism (Fos, Rbx1, BioB genes), membrane injury (Plscr 1 gene) (Wang et al 2009;Polidori et al 2012); reduction of mitochondrial DNA content and increase of reactive oxygen species (ROS) (Potenza et al 2010); activation of ERK signaling cascade (Prina-Mello et al 2006); inactivation of voltage-gated potassium and calcium channels (VGPC, VGCC, respectively) (Jie-Fei et al 2007;Rosen 1996); induction of an increase and decrease in [Ca 2? ] i ions (Prina-Mello et al 2006;Wang et al 2010) to the lower effective dose at the target tissue used in a number of randomized control trials of the therapeutic applications of magnetic fields for pain management, whereas a strength field of 100 mT was used in promising cell culture studies for Parkinson's disease treatment (Harlow et al 2004;Wolsko et al 2004;Wang et al 2010).…”

The effect of whole-body, repetitive, inhomogeneous static magnetic field-exposure on the symptoms of experimental autoimmune encephalomyelitis in mice

“…This implies an even smaller actual current density value. We used the same SMF generator as in earlier experiments [14,25,26,30,37,39,40].…”

“…Not only because several cytokines, such as pro-inflammatory cytokines: IL-6 [28][29][30][31][32][33], IL-8 [29,31,34], tumor necrosis factor-α (TNF-α) [29,32,33,35], and anti-inflammatory cytokine IL-10 [29,32,35], were shown to have a significant contribution to either the development or the evolution of pathological conditions such as EAE or MS, but the release of these cytokines was also investigated under SMF-exposure. It is conceivable that the self-motion of animals in a whole-body SMF may generate currents especially, when animals are free to move as discussed to some details in [25,26,36].…”

Changes in the expression and current of the Na+/K+ pump in the snail nervous system after exposure to static magnetic field

“…This discrepancy could thus be attributed to the aforementioned phosphorylation and dephosphorylation processes (Nikolić et al, 2012) that directly affected activity of the pumps already present in the plasma membrane. Previous data showed that 15min exposure to moderate SMF followed by 30min and 1day recovery caused prominent changes in the expression of genes involved in cellular metabolism in the human embryonic cell line and cultured hippocampal rat neurons, respectively (Hirai et al, 2002;Wang et al, 2009). In our experiments the overall expression of the Na + /K + pump α-subunit was not significantly changed after 15min of exposure to 10mT SMF.…”