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Author |
Ke, X.Q.; Sun, W.J.; Lu, D.Q.; Fu, Y.T.; Chiang, H. |
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Title |
50-Hz magnetic field induces EGF-receptor clustering and activates RAS |
Type |
Journal Article |
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Year |
2008 |
Publication |
International Journal of Radiation Biology |
Abbreviated Journal |
Int J Radiat Biol |
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Volume |
84 |
Issue |
5 |
Pages |
413-420 |
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Keywords |
Animals; Cell Membrane/metabolism; Cluster Analysis; Cricetinae; *Electromagnetic Fields; Fibroblasts/metabolism; *Genes, ras; Glutathione Transferase/metabolism; Immunoprecipitation; Microscopy, Confocal; Microscopy, Fluorescence; Receptor, Epidermal Growth Factor/*chemistry/metabolism; Signal Transduction/radiation effects; p38 Mitogen-Activated Protein Kinases/metabolism; ras Proteins/*metabolism |
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Abstract |
PURPOSE: In a previous study, we found that exposure to a 50 Hz magnetic field (MF) could activate stress-activated protein kinase (SAPK) and P38 mitogen-activated protein (MAP) kinase (P38 MAPK) in Chinese hamster lung (CHL) fibroblast cells, and simultaneous exposure to a 'noise' MF of the same intensity inhibited these effects. In order to explore the possible target sites and upstream signal transduction molecules of SAPK and P38 MAPK, and further validate the interference effects of 'noise' MF on 50 Hz MF, the effects of MF exposure on clustering of epidermal growth factor (EGF) receptors and Ras protein activation were investigated. MATERIALS AND METHODS: CHL cells were exposed to a 50 Hz sinusoidal MF at 0.4 mT for different durations, and clustering of EGF receptors on cellular membrane and Ras protein activation were analyzed using immunofluorescence confocal microscopy and co-precipitation technology. EGF treatment served as the positive control. RESULTS: The results showed that, compared with sham-exposed cells, exposure to a 50 Hz MF at 0.4 mT for 5 min slightly induced EGF receptor clustering, whereas exposure for 15 min enhanced receptor clustering significantly. Corresponding to receptor clustering, Ras protein was also activated after exposure to the 50 Hz MF. Exposure to a 'noise' MF (with frequency ranges from 30 – 90 Hz) at the same intensity and durations, did not significantly affect EGF receptor clustering and Ras protein. However, by superimposing the 'noise' MF, receptor clustering and Ras activation induced by 50 Hz MF were inhibited. CONCLUSION: The results suggested that membrane receptors could be one of the most important targets where extremely low frequency (ELF) MF interacts with cells, and Ras may participate in the signal transduction process of 50 Hz MF. Furthermore, a 'noise' MF could inhibit these effects caused by ELF-MF. |
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Department of Hygiene of Children and Adolescents, Zhejiang University School of Medicine, Hangzhou, China |
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ISSN |
0955-3002 |
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WP5 In vitro |
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PMID:18464070 |
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CBM.UAM @ ccobaleda @ |
Serial |
62 |
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Author |
Schuz, J.; Grigat, J.P.; Stormer, B.; Rippin, G.; Brinkmann, K.; Michaelis, J. |
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Title |
Extremely low frequency magnetic fields in residences in Germany. Distribution of measurements, comparison of two methods for assessing exposure, and predictors for the occurrence of magnetic fields above background level |
Type |
Journal Article |
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Year |
2000 |
Publication |
Radiation and Environmental Biophysics |
Abbreviated Journal |
Radiat Environ Biophys |
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Volume |
39 |
Issue |
4 |
Pages |
233-240 |
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Keywords |
Child; *Electromagnetic Fields; *Environmental Exposure/analysis; Environmental Monitoring/*methods; Germany; *Housing; Humans; Models, Statistical; Odds Ratio; Risk Factors; Time Factors |
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Abstract |
We examined the results of 1,835 magnetic field measurements in German residences conducted between November 1997 and September 1999. The measurements were part of an epidemiological study on the relationship between magnetic fields and childhood leukemia. We performed a fixed-location measurement of the magnetic field at 50 Hz and 16 2/3 Hz (frequency of the German railway system) over 24 h in the child's bedroom in the residence of each study participant. In addition, we conducted a second 24 h-measurement in the living room at 50 Hz, and spot measurements while walking through all rooms of the respective dwelling. Median 50 Hz magnetic fields above 0.2 muT were found to be infrequent in Germany (only 1.4% of all residences). Fields produced by high-voltage power lines (123-420 kV) were lower than expected: the median magnetic field was above 0.2 muT in only 8 (32.0%) of 25 residences located 50 m or closer to a high-voltage power line indicating that power lines in Germany are usually run well below the maximum power load. We found that magnetic fields were correlated with the type of residence and higher magnetic fields were measured in apartment buildings. There was also some evidence for a positive correlation between magnetic fields and traffic density and an inverse association between magnetic fields and family net income. The 24 h-magnetic field measurements correlated well with the spot measurements (r>0.7). However, when dichotomized with a cut-off point of 0.2 muT, there was only a poor agreement between the two measurement methods. A loss of the strength of the association after categorization was also observed when comparing the arithmetic mean and median of the same 24 h-measurement. In summary, these analyses give a valuable overview of magnetic field distributions in German residences. |
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Institut fur Medizinische Statistik und Dokumentation, University of Mainz, Germany. schuez@imsd.uni-mainz.de |
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ISSN |
0301-634X |
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Area |
WP2 Exposure measurements |
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PMID:11200967 |
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CBM.UAM @ ccobaleda @ |
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61 |
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Author |
Nie, K.; Henderson, A. |
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Title |
MAP kinase activation in cells exposed to a 60 Hz electromagnetic field |
Type |
Journal Article |
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Year |
2003 |
Publication |
Journal of Cellular Biochemistry |
Abbreviated Journal |
J Cell Biochem |
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Volume |
90 |
Issue |
6 |
Pages |
1197-1206 |
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Keywords |
Animals; Cell Line/drug effects/*radiation effects; Child; Dose-Response Relationship, Drug; *Electromagnetic Fields; Enzyme Activation; Enzyme Inhibitors/metabolism; Humans; Isoenzymes/antagonists & inhibitors/metabolism; MAP Kinase Signaling System/*physiology; Mitogen-Activated Protein Kinases/*metabolism; Protein Kinase C/antagonists & inhibitors/metabolism; Rats; Tetradecanoylphorbol Acetate/pharmacology |
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Abstract |
This research provides evidence that mitogen-activated protein kinase or extracellular signal-regulated kinase (MAPK/ERK) is activated in HL-60 human leukemia cells, MCF-7 human breast cancer cells, and rat fibroblast 3Y1 cells exposed to a 60 Hertz (Hz), 1 Gauss (G) electromagnetic field (EMF). The effects of EMF exposure were compared to those observed using 12-O-tetradecanoylphorbal-13-acetate (TPA) treatment. The level of MAPK activation in cells exposed to EMF was approximately equivalent to that in cells treated with 0.1-0.5 ng/ml of TPA. A role for protein kinase C (PKC) in the process leading to MAPK activation in EMF exposed cells is also suggested by the results. MAPK activation is negated by an inhibitor to PKCalpha, but not PKCdelta inhibitors, in cells subjected to EMF exposure or TPA treatment. Thus, similarities between the effects of EMF exposure and TPA treatment are supported by this investigation. This provides a possible method for revealing other participants in EMF-cell interaction, since the TPA induction pathway is well documented. |
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Department of Biological Sciences and the Center for Gene Structure and Function, Hunter College of the City University of New York, Graduate Center of the City University of New York, New York, New York 10021, USA |
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0730-2312 |
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WP5 In vitro |
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PMID:14635193 |
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Call Number |
CBM.UAM @ ccobaleda @ |
Serial |
63 |
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Author |
Friedman, J.; Kraus, S.; Hauptman, Y.; Schiff, Y.; Seger, R. |
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Title |
Mechanism of short-term ERK activation by electromagnetic fields at mobile phone frequencies |
Type |
Journal Article |
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Year |
2007 |
Publication |
The Biochemical Journal |
Abbreviated Journal |
Biochem J |
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Volume |
405 |
Issue |
3 |
Pages |
559-568 |
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Keywords |
Animals; Cell Line; Cellular Phone/*instrumentation; *Electromagnetic Fields; Enzyme Activation/radiation effects; Epidermal Growth Factor/metabolism; Extracellular Signal-Regulated MAP Kinases/*metabolism; Humans; Intercellular Signaling Peptides and Proteins; Kinetics; MAP Kinase Kinase 4/metabolism; Phosphorylation; Rats; Reactive Oxygen Species; p38 Mitogen-Activated Protein Kinases/metabolism |
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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. |
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Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel |
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ISSN |
0264-6021 |
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WP5 In vitro |
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PMID:17456048 |
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CBM.UAM @ ccobaleda @ |
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64 |
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Author |
Plotnikov, A.; Zehorai, E.; Procaccia, S.; Seger, R. |
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Title |
The MAPK cascades: signaling components, nuclear roles and mechanisms of nuclear translocation |
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Journal Article |
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Year |
2011 |
Publication |
Biochimica et Biophysica Acta |
Abbreviated Journal |
Biochim Biophys Acta |
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Volume |
1813 |
Issue |
9 |
Pages |
1619-1633 |
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Keywords |
Active Transport, Cell Nucleus/genetics/*physiology; Chromatin Assembly and Disassembly/physiology; Gene Expression Regulation; Genes, Immediate-Early; Humans; MAP Kinase Signaling System/genetics/*physiology; Models, Biological; Nuclear Localization Signals/physiology; Receptors, Cytoplasmic and Nuclear/physiology; Stress, Physiological; Transcription Factors/physiology |
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The MAPK cascades are central signaling pathways that regulate a wide variety of stimulated cellular processes, including proliferation, differentiation, apoptosis and stress response. Therefore, dysregulation, or improper functioning of these cascades, is involved in the induction and progression of diseases such as cancer, diabetes, autoimmune diseases, and developmental abnormalities. Many of these physiological, and pathological functions are mediated by MAPK-dependent transcription of various regulatory genes. In order to induce transcription and the consequent functions, the signals transmitted via the cascades need to enter the nucleus, where they may modulate the activity of transcription factors and chromatin remodeling enzymes. In this review, we briefly cover the composition of the MAPK cascades, as well as their physiological and pathological functions. We describe, in more detail, many of the important nuclear activities of the MAPK cascades, and we elaborate on the mechanisms of ERK1/2 translocation into the nucleus, including the identification of their nuclear translocation sequence (NTS) binding to the shuttling protein importin7. Overall, the nuclear translocation of signaling components may emerge as an important regulatory layer in the induction of cellular processes, and therefore, may serve as targets for therapeutic intervention in signaling-related diseases such as cancer and diabetes. This article is part of a Special Issue entitled: Regulation of Signaling and Cellular Fate through Modulation of Nuclear Protein Import. |
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Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Isreal |
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ISSN |
0006-3002 |
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WP5 In vitro |
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PMID:21167873 |
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Call Number |
CBM.UAM @ ccobaleda @ |
Serial |
65 |
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