Power Frequency Magnetic Fields Affect the p38 MAPK-Mediated Regulation of NB69 Cell Proliferation Implication of Free Radicals

Martínez, María Antonia; Úbeda, Alejandro; Moreno, José Luis Ocaña; Trillo, María Ángeles

doi:10.3390/ijms17040510

Cited by 23 publications

(40 citation statements)

References 80 publications

(123 reference statements)

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“…A 12-day exposure to a 50 Hz, 1 mT ELF-MF has been reported to increase SIRT1 level in mesenchymal stem cells from adult bone marrow 46 , whereas transcranial magnetic stimulation with an ELF field has been proven to upregulate NRF2 in a rat model of Huntington’s disease 45 . Since SIRT1 and SIRT3 overexpression has been previously shown to elicit cytoprotective action in SH-SY5Y against oxidative stress-promoting challenges 70 , 71 , the distinctive pattern of biochemical and molecular responses we observed in MF-exposed cells corroborate the idea that the interaction between ELF-MF and biosystems may activate redox-responsive processes, as hypothesized by us and others 19 , 20 , 25 , 26 , 72 , 73 .…”

Section: Discussionsupporting

confidence: 87%

Power frequency magnetic field promotes a more malignant phenotype in neuroblastoma cells via redox-related mechanisms

Falone

Santini

Cordone

et al. 2017

Sci Rep

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In accordance with the classification of the International Agency for Research on Cancer, extremely low frequency magnetic fields (ELF-MF) are suspected to promote malignant progression by providing survival advantage to cancer cells through the activation of critical cytoprotective pathways. Among these, the major antioxidative and detoxification defence systems might be targeted by ELF-MF by conferring cells significant resistance against clinically-relevant cytotoxic agents. We investigated whether the hyperproliferation that is induced in SH-SY5Y human neuroblastoma cells by a 50 Hz, 1 mT ELF magnetic field was supported by improved defence towards reactive oxygen species (ROS) and xenobiotics, as well as by reduced vulnerability against both H2O2 and anti-tumor ROS-generating drug doxorubicin. ELF-MF induced a proliferative and survival advantage by activating key redox-responsive antioxidative and detoxification cytoprotective pathways that are associated with a more aggressive behavior of neuroblastoma cells. This was coupled with the upregulation of the major sirtuins, as well as with increased signaling activity of the erythroid 2-related nuclear transcription factor 2 (NRF2). Interestingly, we also showed that the exposure to 50 Hz MF as low as 100 µT may still be able to alter behavior and responses of cancer cells to clinically-relevant drugs.

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Section: Discussionsupporting

confidence: 87%

Power frequency magnetic field promotes a more malignant phenotype in neuroblastoma cells via redox-related mechanisms

Falone

Santini

Cordone

et al. 2017

Sci Rep

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“…Some available studies provide hints that MF also acts like a mild stressor. For example, after MF exposure (100 µT, 50 Hz) an induced transient activation of p38, JNK and ERK1/2 was shown in NB69 cells accompanied by changes in the cell cycle progression ( 73 ). The authors showed that the MF-induced proliferative effects were exerted through sequential upregulation of MAPK-p38 and ERK1/2 activation and that the upregulation likely was mediated by a ROS-dependent activation of p38.…”

Section: Summary and Concluding Remarksmentioning

confidence: 99%

Cellular Response to ELF-MF and Heat: Evidence for a Common Involvement of Heat Shock Proteins?

Zeni

Simkó²,

Scarfì

et al. 2017

Front. Public Health

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It has been shown that magnetic fields in the extremely low frequency range (ELF-MF) can act as a stressor in various in vivo or in vitro systems, at flux density levels below those inducing excitation of nerve and muscle cells, which are setting the limits used by most generally accepted exposure guidelines, such as the ones published by the International Commission on Non-Ionizing Radiation Protection. In response to a variety of physiological and environmental factors, including heat, cells activate an ancient signaling pathway leading to the transient expression of heat shock proteins (HSPs), which exhibit sophisticated protection mechanisms. A number of studies suggest that also ELF-MF exposure can activate the cellular stress response and cause increased HSPs expression, both on the mRNA and the protein levels. In this review, we provide some of the presently available data on cellular responses, especially regarding HSP expression, due to single and combined exposure to ELF-MF and heat, with the aim to compare the induced effects and to detect possible common modes of action. Some evidence suggest that MF and heat can act as costressors inducing a kind of thermotolerance in cell cultures and in organisms. The MF exposure might produce a potentiated or synergistic biological response such as an increase in HSPs expression, in combination with a well-defined stress, and in turn exert beneficial effects during certain circumstances.

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“…Importantly, the activation of the MAPKs and Akt by both shortterm and long-term exposure to ELF-MF has been demonstrated [33,34]. Effects of ERKs and Akt due to short-term (30 min) exposures have been found in various systems, including HL-60, MCF7, 3Y1, HTB124, HaCaT, and NB69 cells [33][34][35][36]. Activatory phosphorylation of stress-related MAPKs, JNK, and p38 by ELF-MF has been demonstrated as well in CHL cells exposed to 50 Hz for 3 -15 min [37][38][39], and in NB69 cells exposed to 50 Hz ELF-MF for 15, 30, or 60 min [33].…”

Section: Introductionmentioning

confidence: 98%

“…Dysregulation of these five signaling pathways is involved in the induction and maintenance of many pathologies, including cancer, diabetes, and autoimmunity [18,32]. Importantly, the activation of the MAPKs and Akt by both shortterm and long-term exposure to ELF-MF has been demonstrated [33,34]. Effects of ERKs and Akt due to short-term (30 min) exposures have been found in various systems, including HL-60, MCF7, 3Y1, HTB124, HaCaT, and NB69 cells [33][34][35][36].…”

Section: Introductionmentioning

confidence: 99%

“…Effects of ERKs and Akt due to short-term (30 min) exposures have been found in various systems, including HL-60, MCF7, 3Y1, HTB124, HaCaT, and NB69 cells [33][34][35][36]. Activatory phosphorylation of stress-related MAPKs, JNK, and p38 by ELF-MF has been demonstrated as well in CHL cells exposed to 50 Hz for 3 -15 min [37][38][39], and in NB69 cells exposed to 50 Hz ELF-MF for 15, 30, or 60 min [33]. Although production of reactive oxygen species (ROS) [40] or aggregation of receptors [21] has been implicated in the ELF-MF response, the mechanisms by which exposure to ELF-MF is sensed by cells to induce MAPK activation remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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Activation of Signaling Cascades by Weak Extremely Low Frequency Electromagnetic Fields

Kapri-Pardes

Hanoch

Maik-Rachline

et al. 2017

Cell Physiol Biochem

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Background/Aims:Results from recent studies suggest that extremely low frequency magnetic fields (ELF-MF) interfere with intracellular signaling pathways related to proliferative control. The mitogen-activated protein kinases (MAPKs), central signaling components that regulate essentially all stimulated cellular processes, include the extracellular signal-regulated kinases 1/2 (ERK1/2) that are extremely sensitive to extracellular cues. Anti-phospho-ERK antibodies serve as a readout for ERK1/2 activation and are able to detect minute changes in ERK stimulation. The objective of this study was to explore whether activation of ERK1/2 and other signaling cascades can be used as a readout for responses of a variety of cell types, both transformed and non-transformed, to ELF-MF. Methods: We applied ELF-MF at various field strengths and time periods to eight different cell types with an exposure system housed in a tissue culture incubator and followed the phosphorylation of MAPKs and Akt by western blotting. Results: We found that the phosphorylation of ERK1/2 is increased in response to ELF-MF. However, the phosphorylation of ERK1/2 is likely too low to induce ELF-MF-dependent proliferation or oncogenic transformation. The p38 MAPK was very slightly phosphorylated, but JNK or Akt were not. The effect on ERK1/2 was detected for exposures to ELF-MF strengths as low as 0.15 µT and was maximal at ~10 µT. We also show that ERK1/2 phosphorylation is blocked by the flavoprotein inhibitor diphenyleneiodonium, indicating that the response to ELF-MF may be exerted via NADP oxidase similar to the phosphorylation of ERK1/2 in response to microwave radiation. Conclusions: Our results further indicate that cells are responsive to ELF-MF at field strengths much lower than previously suspected and that the effect may be mediated by NADP oxidase. However, the small increase in ERK1/2 phosphorylation is probably insufficient to affect proliferation and oncogenic transformation. Therefore, the results cannot be regarded as proof of the involvement of ELF-MF in cancer in general or childhood leukemia in particular.

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Power Frequency Magnetic Fields Affect the p38 MAPK-Mediated Regulation of NB69 Cell Proliferation Implication of Free Radicals

Cited by 23 publications

References 80 publications

Power frequency magnetic field promotes a more malignant phenotype in neuroblastoma cells via redox-related mechanisms

Power frequency magnetic field promotes a more malignant phenotype in neuroblastoma cells via redox-related mechanisms

Cellular Response to ELF-MF and Heat: Evidence for a Common Involvement of Heat Shock Proteins?

Activation of Signaling Cascades by Weak Extremely Low Frequency Electromagnetic Fields

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