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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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Address |
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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ISSN |
0730-2312 |
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WP5 In vitro |
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Notes |
PMID:14635193 |
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no |
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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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Abstract |
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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Call Number |
CBM.UAM @ ccobaleda @ |
Serial |
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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Abstract |
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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Notes |
PMID:21167873 |
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Call Number |
CBM.UAM @ ccobaleda @ |
Serial |
65 |
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Author |
Keshet, Y.; Seger, R. |
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Title |
The MAP kinase signaling cascades: a system of hundreds of components regulates a diverse array of physiological functions |
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Journal Article |
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Year |
2010 |
Publication |
Methods in Molecular Biology (Clifton, N.J.) |
Abbreviated Journal |
Methods Mol Biol |
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Volume |
661 |
Issue |
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Pages |
3-38 |
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Keywords |
Animals; Extracellular Signal-Regulated MAP Kinases/metabolism; Humans; JNK Mitogen-Activated Protein Kinases/metabolism; *MAP Kinase Signaling System; p38 Mitogen-Activated Protein Kinases/metabolism |
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Abstract |
Sequential activation of kinases within the mitogen-activated protein (MAP) kinase (MAPK) cascades is a common, and evolutionary-conserved mechanism of signal transduction. Four MAPK cascades have been identified in the last 20 years and those are usually named according to the MAPK components that are the central building blocks of each of the cascades. These are the extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-Terminal kinase (JNK), p38, and ERK5 cascades. Each of these cascades consists of a core module of three tiers of protein kinases termed MAPK, MAPKK, and MAP3K, and often two additional tiers, the upstream MAP4K and the downstream MAPKAPK, which can complete five tiers of each cascade in certain cell lines or stimulations. The transmission of the signal via each cascade is mediated by sequential phosphorylation and activation of the components in the sequential tiers. These cascades cooperate in transmitting various extracellular signals and thus control a large number of distinct and even opposing cellular processes such as proliferation, differentiation, survival, development, stress response, and apoptosis. One way by which the specificity of each cascade is regulated is through the existence of several distinct components in each tier of the different cascades. About 70 genes, which are each translated to several alternatively spliced isoforms, encode the entire MAPK system, and allow the wide array of cascade's functions. These components, their regulation, as well as their involvement together with other mechanisms in the determination of signaling specificity by the MAPK cascade is described in this review. Mis-regulation of the MAPKs signals usually leads to diseases such as cancer and diabetes; therefore, studying the mechanisms of specificity-determination may lead to better understanding of these signaling-related diseases. |
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Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel |
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ISSN |
1064-3745 |
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WP5 In vitro |
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Notes |
PMID:20811974 |
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Call Number |
CBM.UAM @ ccobaleda @ |
Serial |
66 |
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Author |
Brix, J.; Wettemann, H.; Scheel, O.; Feiner, F.; Matthes, R. |
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Title |
Measurement of the individual exposure to 50 and 16 2/3 Hz magnetic fields within the Bavarian population |
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Journal Article |
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Year |
2001 |
Publication |
Bioelectromagnetics |
Abbreviated Journal |
Bioelectromagnetics |
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Volume |
22 |
Issue |
5 |
Pages |
323-332 |
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Keywords |
Adolescent; Adult; Environmental Exposure; Female; Germany; Housing; Humans; *Magnetics/*adverse effects; Male; Middle Aged; Occupational Exposure; Time Factors |
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Abstract |
This study investigates the individual magnetic field exposures at 16 2/3 and 50 Hz of 1952 people, selected from the Bavarian population. Personal flux density meters (“Field Watcher FW2A”) were worn by the participants for 24 h. Every second, the flux density was recorded for both frequencies and for the three spatial axes (dynamic range per axis: several nT up to 100 microT at 50 Hz, 150 microT at 16 2/3 Hz). For 50 Hz fields, the mean of the 1,952 individual means was 0.101 microT and that of the individual medians was 0.047 microT. High level exposures occurred mainly during working hours. Only 2.4% of the subjects showed individual medians higher than 0.2 microT. About 53% of all volunteers were working on the day of recording. Levels for craftsmen (n = 148; mean individual mean: 0.166 microT) were generally higher than those for office workers (n = 624; mean individual mean: 0.107 microT). Flux densities exceeding 100 microT at 50 Hz were measured in 31 persons. The total time with such extreme exposures amounts to nearly 21 min, less than 0.001% of the total time for all measurements (5.3 years). To our knowledge, this is the first exposure study where 16 2/3 Hz magnetic fields (caused by electrified railways) have additionally been monitored over 24 h. For persons living next to railway lines, the mean individual mean (0.156 microT) and mean individual median (0.102 microT) were calculated. Over all, the mean exposures are only 0.1% of the magnetic flux density limit for 50 Hz (100 microT) and about 0.05% of the limit (300 microT) for 16 2/3 Hz recommended by the International Commission on Non-Ionizing Radiation Protection. |
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Federal Office for Radiation Protection, Oberschleisshem (Neuherberg), Germany. jbrix@bfs.de |
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ISSN |
0197-8462 |
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Area |
WP2 Exposure measurements |
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Notes |
PMID:11424155 |
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Call Number |
Swiss TPH @ martin.roosli @ |
Serial |
67 |
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