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Exposure of murine cells to pulsed electromagnetic fields rapidly activates the mTOR signaling pathway
Thomas E Patterson1, Yoshitada Sakai, Mark D Grabiner
1Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Abstract:
Murine pre-osteoblasts and fibroblast cell lines were used to determine the effect of pulsed electromagnetic field (PEMF) exposure on the production of autocrine growth factors and the activation of early signal transduction pathways. Exposure of pre-osteoblast cells to PEMF minimally increased the amount of secreted TGF-beta after 1 day, but had no significant effects thereafter. PEMF exposure of pre-osteoblast cells also had no effect on the amount of prostaglandin E(2) in the conditioned medium. Exposure of both pre-osteoblasts and fibroblasts to PEMF rapidly activated the mTOR signaling pathway, as evidenced by increased phosphorylation of mTOR, p70 S6 kinase, and the ribosomal protein S6. Inhibition of PI3-kinase activity with the chemical inhibitor LY294002 blocked PEMF-dependent activation of mTOR in both the pre-osteoblast and fibroblast cell lines. These findings suggest that PEMF exposure might function in a manner analogous to soluble growth factors by activating a unique set of signaling pathways, inclusive of the PI-3 kinase/mTOR pathway.
Insights
Pulsed electromagnetic field (PEMF) exposure rapidly activates the mTOR signaling pathway in pre-osteoblasts and fibroblasts. This activation, mediated by PI3-kinase, suggests PEMF may mimic growth factors.
Area of Science:
- Cell Biology
- Biophysics
- Biochemistry
Background:
- Pulsed electromagnetic field (PEMF) therapy is explored for various biological effects.
- Understanding PEMF's impact on cellular signaling is crucial for therapeutic applications.
- Autocrine growth factors and signal transduction pathways are key regulators of cellular processes.
Purpose of the Study:
- To investigate the effect of PEMF on autocrine growth factor production in murine pre-osteoblasts.
- To determine PEMF's influence on early signal transduction pathways in pre-osteoblasts and fibroblasts.
- To elucidate the specific signaling cascade involved in PEMF-induced cellular responses.
Main Methods:
- Murine pre-osteoblast and fibroblast cell lines were utilized.
- Cells were exposed to PEMF, and conditioned media were analyzed for TGF-beta and prostaglandin E(2).
- Western blotting was employed to assess the phosphorylation status of mTOR, p70 S6 kinase, and ribosomal protein S6.
- The PI3-kinase inhibitor LY294002 was used to investigate pathway dependency.
Main Results:
- PEMF exposure minimally increased TGF-beta secretion in pre-osteoblasts on day 1, with no sustained effect.
- PEMF did not significantly alter prostaglandin E(2) levels in pre-osteoblasts.
- Rapid and significant activation of the mTOR signaling pathway (increased phosphorylation of mTOR, p70 S6K, S6) was observed in both cell types upon PEMF exposure.
- Inhibition of PI3-kinase activity abolished PEMF-induced mTOR activation.
Conclusions:
- PEMF exposure activates the PI3-kinase/mTOR signaling pathway in pre-osteoblasts and fibroblasts.
- This activation occurs rapidly and is dependent on PI3-kinase activity.
- PEMF may exert its biological effects by activating signaling pathways, potentially mimicking soluble growth factors.
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