Moderate strength (0.23-0.28 T) static magnetic fields (SMF) modulate signaling and differentiation in human embryonic cells.
BACKGROUND
Compelling 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.


RESULTS
Software 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.


CONCLUSIONS
This 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.
Wang
Zhiyun
Z
Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD, USA. zhiyun_wang@hotmail.com
Sarje
Anshu
A
Che
Pao-Lin
PL
Yarema
Kevin J
KJ
D015415:Biomarkers; D002454:Cell Differentiation; D002460:Cell Line; D004622:Embryo, Mammalian / Q000166:cytology*; D005732:Gangliosides / Q000378:metabolism / Q000494:pharmacology; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008280:Magnetics; D012333:RNA, Messenger / Q000378:metabolism; D012984:Software; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014158:Transcription, Genetic
D015415:Biomarkers; D005732:Gangliosides; D015850:Interleukin-6; D012333:RNA, Messenger; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4