Induction of Neuritogenesis in PC12 Cells by a Pulsed Electromagnetic Field via MEK-ERK1/2 Signaling

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  • Kudo Tada-aki
    Division of Oral Physiology, Tohoku University Graduate School of Dentistry
  • Kanetaka Hiroyasu
    Liaison Center for Innovative Dentistry, Tohoku University Graduate School of Dentistry
  • Shimizu Yoshinaka
    Division of Oral Pathology, Tohoku University Graduate School of Dentistry
  • Abe Toshihiko
    Institute of Field Generation
  • Mori Hitoshi
    Institute of Field Generation
  • Mori Kazumi
    Institute of Field Generation
  • Suzuki Eizaburo
    Department of Physical Medicine and Rehabilitation, Tohoku University Graduate School of Medicine
  • Takagi Toshiyuki
    Institute of Fluid Science, Tohoku University
  • Izumi Shin-ichi
    Tohoku University Graduate School of Biomedical Engineering Department of Physical Medicine and Rehabilitation, Tohoku University Graduate School of Medicine

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We examined the regulation of neuritogenesis by a pulsed electromagnetic field (PEMF) in rat PC12 pheochromocytoma cells, which can be induced to differentiate into neuron-like cells with elongated neurites by inducers such as nerve growth factor (NGF). Plated PC12 cells were exposed to a single PEMF (central magnetic flux density, 700 mT; frequency, 0.172 Hz) for up to 12 h per day and were then evaluated for extent of neuritogenesis or acetylcholine esterase (AChE) activity. To analyze the mechanism underlying the effect of the PEMF on the cells, its effects on intracellular signaling were examined using the ERK kinase (MEK) inhibitors PD098059 and U0126 (U0124 was used as a negative control for U0126). The number of neurite-bearing PC12 cells and AChE activity increased after PEMF exposure without the addition of other inducers of neuritogenesis. Additionally, PEMF exposure induced sustained activation of ERK1/2 in PC12 cells, but not in NR8383 rat alveolar macrophages. Furthermore, U0126 strongly inhibited PEMF-dependent ERK1/2 activation and neuritogenesis. The PEMF-dependent neuritogenesis was also suppressed by PD098059, but not U0124. These results suggest that PEMF stimulation independently induced neuritogenesis and that activation of MEK-ERK1/2 signaling was induced by a cell-type-dependent mechanism required for PEMF-dependent neuritogenesis in PC12 cells.

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