Study on cellular and molecular mechanisms underline the biological effects of extremely low frequency electromagnetic fields (ELF EMFs)

In the last decades, electromagnetic therapy generated an intense interest due to its use for the treatment of some pathological states related to musculoskeletal system. In particular, electromagnetic fields (EMFs) provide a therapeutic tool used to improve tissue regeneration in bone non-union fractures, to facilitate skin wound healing and to reduce pain symptomatology. This therapy represents a valid and non-invasive approach widely used to treat the area of interest avoiding side effects and the FDA approved its use to treat bone disorders. This therapy uses the electromagnetic radiations in the frequency range between 3 Hz and 300 Hz. These are non-ionizing and low energy radiations capable to induce heterogeneous effects on a very large number of biological processes such as cell cycle distribution and proliferation, apoptosis and cell migration. All of these effects vary in relation to frequency, amplitude, length of exposure and are also related to the intrinsic susceptibility of different cell lines. This aspect makes molecular investigations complicated because the cellular response is strictly related to the electromagnetic treatment used to irradiate samples. Since the mechanism of action by which this physical stimulus acts on cells is still lacking, our efforts have been addressed to define a coherent biochemical and molecular picture, considering the activities of the key enzymes of the most important metabolic pathways. Decreasing level in PKasic activity was found in cells exposed to ELF EMFs and this effect was associated with the inhibition of the isoform M2 of PK which is expressed in our cellular model. In literature, it has been described that this isoform is inhibited by a redox mechanism which cause the oxidation of the Cys358 residue, promoting a metabolic shift toward an anabolic state. Our biochemical results indicate that ELF EMFs treatments seem to elicit a similar response in NIH3T3 cells. Moreover cell migration and proliferation, the two biological processes involved in wound healing process, has been studied using in vitro scratch assay in order to modeling the dynamic of the wound closure.