Mechanism of short-term ERK activation by electromagnetic fields at mobile phone frequencies.
The exposure to non-thermal microwave electromagnetic fields generated by mobile phones affects the expression of many proteins. This effect on transcription and protein stability can be mediated by the MAPK (mitogen-activated protein kinase) cascades, which serve as central signalling pathways and govern essentially all stimulated cellular processes. Indeed, long-term exposure of cells to mobile phone irradiation results in the activation of p38 as well as the ERK (extracellular-signal-regulated kinase) MAPKs. In the present study, we have studied the immediate effect of irradiation on the MAPK cascades, and found that ERKs, but not stress-related MAPKs, are rapidly activated in response to various frequencies and intensities. Using signalling inhibitors, we delineated the mechanism that is involved in this activation. We found that the first step is mediated in the plasma membrane by NADH oxidase, which rapidly generates ROS (reactive oxygen species). These ROS then directly stimulate MMPs (matrix metalloproteinases) and allow them to cleave and release Hb-EGF [heparin-binding EGF (epidermal growth factor)]. This secreted factor activates the EGF receptor, which in turn further activates the ERK cascade. Thus this study demonstrates for the first time a detailed molecular mechanism by which electromagnetic irradiation from mobile phones induces the activation of the ERK cascade and thereby induces transcription and other cellular processes.
Friedman
Joseph
J
Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel.
Kraus
Sarah
S
Hauptman
Yirmi
Y
Schiff
Yoni
Y
Seger
Rony
R
D000818:Animals; D002460:Cell Line; D040421:Cell Phone / Q000295:instrumentation*; D004574:Electromagnetic Fields; D004789:Enzyme Activation / Q000528:radiation effects; D004815:Epidermal Growth Factor / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007700:Kinetics; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017382:Reactive Oxygen Species; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
C587883:HBEGF protein, human; C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D017382:Reactive Oxygen Species; D004815:Epidermal Growth Factor; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4