Author: Yap JLY#1,2, Tai YK#1,2, Fröhlich J1,3, Fong CHH1,2, Yin JN1,2, Foo ZL1,2, Ramanan S1,2, Beyer C3,4, Toh SJ1,2, Casarosa M5, Bharathy N6,7, Kala MP6, Egli M8, Taneja R6, Lee CN1,9, Franco-Obregón A1,2,6,9
1Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
2BioIonic Currents Electromagnetic Pulsing Systems (BICEPS) Laboratory, National University of Singapore, Singapore.
3Institute for Electromagnetic Fields, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland.
4Centre Suisse d'Électronique et de Microtechnique (CSEM SA), Neuchâtel, Switzerland.
5Department of Experimental and Clinical Biomedical Sciences Mario Serio, University of Florence, Florence, Italy.
6Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
7Children's Cancer Therapy Development Institute, Beaverton, Oregon, USA.
8Institute of Medical Engineering, Lucerne University of Applied Sciences and Arts, Hergiswil, Switzerland; and.
9Institute for Health Innovation and Technology, iHealthtech, National University of Singapore, Singapore.
Conference/Journal: FASEB J.
Date published: 2019 Sep 13
Other: Volume ID: fj201900057R , Special Notes: doi: 10.1096/fj.201900057R. [Epub ahead of print] , Word Count: 300
We show that both supplemental and ambient magnetic fields modulate myogenesis. A lone 10 min exposure of myoblasts to 1.5 mT amplitude supplemental pulsed magnetic fields (PEMFs) accentuated in vitro myogenesis by stimulating transient receptor potential (TRP)-C1-mediated calcium entry and downstream nuclear factor of activated T cells (NFAT)-transcriptional and P300/CBP-associated factor (PCAF)-epigenetic cascades, whereas depriving myoblasts of ambient magnetic fields slowed myogenesis, reduced TRPC1 expression, and silenced NFAT-transcriptional and PCAF-epigenetic cascades. The expression levels of peroxisome proliferator-activated receptor γ coactivator 1α, the master regulator of mitochondriogenesis, was also enhanced by brief PEMF exposure. Accordingly, mitochondriogenesis and respiratory capacity were both enhanced with PEMF exposure, paralleling TRPC1 expression and pharmacological sensitivity. Clustered regularly interspaced short palindromic repeats-Cas9 knockdown of TRPC1 precluded proliferative and mitochondrial responses to supplemental PEMFs, whereas small interfering RNA gene silencing of TRPM7 did not, coinciding with data that magnetoreception did not coincide with the expression or function of other TRP channels. The aminoglycoside antibiotics antagonized and down-regulated TRPC1 expression and, when applied concomitantly with PEMF exposure, attenuated PEMF-stimulated calcium entry, mitochondrial respiration, proliferation, differentiation, and epigenetic directive in myoblasts, elucidating why the developmental potential of magnetic fields may have previously escaped detection. Mitochondrial-based survival adaptations were also activated upon PEMF stimulation. Magnetism thus deploys an authentic myogenic directive that relies on an interplay between mitochondria and TRPC1 to reach fruition.-Yap, J. L. Y., Tai, Y. K., Fröhlich, J., Fong, C. H. H., Yin, J. N., Foo, Z. L., Ramanan, S., Beyer, C., Toh, S. J., Casarosa, M., Bharathy, N., Kala, M. P., Egli, M., Taneja, R., Lee, C. N., Franco-Obregón, A. Ambient and supplemental magnetic fields promote myogenesis via a TRPC1-mitochondrial axis: evidence of a magnetic mitohormetic mechanism.
KEYWORDS: PGC-1α; calcineurin; mitochondriogenesis; pulsed electromagnetic fields; reactive oxygen species
PMID: 31518158 DOI: 10.1096/fj.201900057R