Activation of signal-transduction mechanisms may underlie the therapeutic effects of an applied electric field

Glucose Uptake in Rat Skeletal Muscle L6 Cells Is Increased by Low-Intensity Electrical Current Through the Activation of the Phosphatidylinositol-3-OH Kinase (PI-3K) / Akt Pathway

“…This is consistent with a recent study showing that there is a mechanistic difference between in vivo exercise (which causes muscle contraction) and low-intensity electrical current in terms of their effects on elevating the insulin-stimulated glucose transport in skeletal muscle (10). It has been postulated that low-intensity electrical fields can impact on cellular functions by enhancing intracellular signal transduction and that this effect is the basis for the observed therapeutic benefits of applied low-intensity electrical current (11,12). In addition, some studies suggested that physiological electrical current (approximately 1 V/cm) activates integrins (13,14), which leads to the up-regulation of the PI-3K/Akt pathway as a protective cellular response to the electrical signal (15).…”

Mild Electrical Stimulation at 0.1-ms Pulse Width Induces p53 Protein Phosphorylation and G2 Arrest in Human Epithelial Cells

“…Given the mounting evidence on the positive effects of exogenous electrical current, it is not surprising that it has been employed in a clinical setting (2,7,8), notwithstanding that the molecular mechanisms of its action are not well understood. A possible mechanism of the effects of applied electrical stimulation could be the activation of signal transduction pathways, as proposed by Seegers et al (9). Indeed, studies by our group and others have demonstrated that electrical stimulation activates the PI3K-Akt pathway, resulting in the process of wound healing (10) and amelioration of hyperglycemia (11,12).…”

“…In the latter disease model, MES was shown to activate not only the PI3K-Akt pathway but also the p38 MAPK signaling pathway (18). It is not surprising that, like other forms of physiological mechanical stresses such as shear stress, MES can activate the signal transduction pathways described above (9,19). Because we found previously that MES exerts protective effects (11,14,18) and other reports have shown that electrical current impedes tumor cell proliferation (20,21), we asked whether MES affects the expression of p53, a tumor suppressor known for its cell-protective functions via a network of signaling pathways.…”

Mild electrical stimulation with heat stimulation increase heat shock protein 70 in articular chondrocyte

“…While it is true that the detailed intracellular mechanisms for the positive effect of low-intensity direct electrical current remain unknown, this beneficial effect may be due to the activation of proteins, including proteins of the signal transduction pathway. 11 In the future, a more detailed elucidation of the effects of MES on intracellular signaling will be necessary.…”

“…11 The positive clinical effects of MES include decreased inflammation, wound healing, and alleviation of pain. 12,13 In recent years, we have shown that MES increases HSP70 via the inhibition of protein degradation by the ubiquitin-proteasome pathway in A549 cells, 14 and that MES increases glucose uptake in the skeletal rat muscle (L6) cells.…”