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Biochemical Journal (2007) 405: 559-568

Mechanism of short-term ERK activation by electromagnetic fields at mobile phone frequencies

Martes 1ro de enero de 2008 · 1356 lecturas

Biochem. J. (2007) 405 (559-568) (Printed in Great Britain)

Mechanism of short-term ERK activation by electromagnetic fields at mobile phone frequencies
Joseph FRIEDMAN*, Sarah KRAUS*, Yirmi HAUPTMAN, Yoni SCHIFF and Rony SEGER*1

*Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel, and Gal Safe Ltd, Rishon Lezion, Israel 75153

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.

Key words: extracellular-signal-regulated kinase (ERK), heparin-binding epidermal growth factor (Hb-EGF), matrix metalloproteinase (MMP), mobile phone irradiation, NADH oxidase, reactive oxygen species (ROS).

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