Auteurs
Moisescu MG, Leveque P, Verjus M-A, Kovacs E, Mir LM. 900 MHz modulated electromagnetic fields accelerate the clathrin-mediated endocytosis pathway. Bioelectromagnetics Ahead of print December 12, 2008 DOI 10.1002/bem.20463 

Background
To understand the nature of the interaction of electromagnetic fields (EMFs) with living cells, it is important to reveal biological parameters susceptible to modification by exposure to these fields. Endocytosis is a basic cellular mechanism contributing to the continuous exchange of molecules between the environment and the cells. During endocytosis, a small portion of the cell membrane invaginates and forms an endocytic vesicle. It encloses macromolecules bound to transmembrane receptors (receptor mediated endocytosis) as well as a small portion of extracellular fluid (fluid phase endocytosis, or pinocytosis). Cell membrane area is restored by the reciprocal mechanism called exocytosis. Several molecular mechanisms for endocytosis are described: clathrin-dependent endocytosis, caveolin-mediated endocytosis, macropinocytosis, and claritin- and caveolin-independent endocytosis. Despite the importance of endocytosis in cell physiology, studies regarding EMF effects on this cellular event are scarce, and their results are controversial.

Objective
In their previous article, the authors have shown an increased uptake of Lucifer Yellow (LY) and of FICT-dextrans by three different cell lines exposed to 900 MHz GSM modulated EMF. It was demonstrated that increased endocytosis was due to the electrical component of the GSM signals. The present article provides information on the mechanisms underlying this endocytosis stimulation, determining the endocytosis pathway affected by GSM signals.

Methods
B16F10 metastatic murine melanoma cells were exposed to LY (fluorescent dye) under GSM-EMF exposure at a specific absorption rate (SAR) of 3.2 W/kg known to be above the threshold needed to induce the effect. Since previous experiments demonstrated that electrical component of the GSM field was responsible for endocytosis enhancement, the cells were also exposed to 217 Hz, 576 ms pulse width, 4 V/cm pulsed electric fields (PEF), similar to this component. Sham exposed cells were used as control. The experiments were performed under controlled temperature in the range of 28.5-29.5°C. The exposures were conducted in the presence of inhibitors of the clathrin- or the caveolin-dependent endocytosis (Chlorpromazine, Filipin, and ethanol). Chlorpromazine and Filipin were used in GSM-EMF experiments, and ethanol – in PEF experiments.

Results
Exposure to both GSM-EMF and PEF enhanced endocytosis in B16F10 metastatic murine melanoma cells. Chlorpromazine blocked the increase in endocytosis provoked by GSM-EMF exposure, while this increase was not significantly affected by Filipin treatment. Ethanol blocked the PEF-stimulated increase in endocytosis.

 

Interpretation
Since all the experiments were conducted under controlled temperatures, the observed increase in LY uptake after GSM-EMF or PEF exposure was not a thermal effect. Chlorpromazine is a known inhibitor of the clathrin – mediated pathway of endocytosis. The GSM-EMF induced increase in LY uptake was abolished by Chlorpromazine administration, which demonstrates that clathrin-mediated pathway was instrumental in the GSM-EMF stimulation. The observation that ethanol, another inhibitor of the clathrin-mediated pathway, produces an effect similar to Chlorpromazine, strengthens this result. Filipin, a known inhibitor of the caveolin-mediated pathway, did not interfere with the GSM-EMF-induced increase in LY uptake. At the first glance, it could be concluded that the inhibition of the caveolin-dependent pathway did not prevent the GSM-EMF stimulation of the endocytosis. However, it is not possible to validate this conclusion without supplementary experiments.

Conclusion
The results of these experiments suggest that the mechanism of endocytosis affected by GSM-EMF exposure involves mainly the clathrin-mediated pathway.

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