The Proliferative Response of NB69 Human Neuroblastoma Cells to a 50 Hz Magnetic Field is mediated by ERK1/2 Signaling

Martínez, María Antonia; Úbeda, Alejandro; Cid, María Antonia; Trillo, María Ángeles

doi:10.1159/000178457

Cited by 37 publications

(63 citation statements)

References 48 publications

(53 reference statements)

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“…Among these pathways, the mitogen-activated protein kinases (MAPK-ERK1/2) are molecules typically involved in transduction of proliferative signals from extracellular origin. The family of serine/threonine kinases to which ERK belong, can be activated by a large variety of chemical [47] and physical stimuli [54,55,56]. ERK1 and ERK2 are fully activated through phosphorylation by MEKs (MAPK/ERK kinases).…”

Section: Discussionmentioning

confidence: 99%

Electric Stimulation at 448 kHz Promotes Proliferation of Human Mesenchymal Stem Cells

Hernández-Bule¹,

Paı́no²,

Trillo³

et al. 2014

Cell Physiol Biochem

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108

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Background/Aims: Capacitive-resistive electric transfer (CRET) is a non invasive electrothermal therapy that applies electric currents within the 400 kHz - 450 kHz frequency range to the treatment of musculoskeletal lesions. Evidence exists that electric currents and electric or magnetic fields can influence proliferative and/or differentiating processes involved in tissue regeneration. This work investigates proliferative responses potentially underlying CRET effects on tissue repair. Methods: XTT assay, flow cytometry, immunofluorescence and Western Blot analyses were conducted to asses viability, proliferation and differentiation of adipose-derived stem cells (ADSC) from healthy donors, after short, repeated (5 m On/4 h Off) in vitro stimulation with a 448-kHz electric signal currently used in CRET therapy, applied at a subthermal dose of 50 μA/mm²Results: The treatment induced PCNA and ERK1/2 upregulation, together with significant increases in the fractions of ADSC undergoing cycle phases S, G₂ and M, and enhanced cell proliferation rate. This proliferative effect did not compromise the multipotential ability of ADSC for subsequent adipogenic, chondrogenic or osteogenic differentiation. Conclusions: These data identify cellular and molecular phenomena potentially underlying the response to CRET and indicate that CRET-induced lesion repair could be mediated by stimulation of the proliferation of stem cells present in the injured tissues.

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Section: Discussionmentioning

confidence: 99%

Electric Stimulation at 448 kHz Promotes Proliferation of Human Mesenchymal Stem Cells

Hernández-Bule¹,

Paı́no²,

Trillo³

et al. 2014

Cell Physiol Biochem

Self Cite

108

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“…In addition, the magnitudes of the AC fields were also different between the GMF and HMF conditions. Considering the fact that the AC magnetic field could affect the signal transduction in the MAPK pathway [77,78], conducting experiments to discriminate between the effects of the AC and DC magnetic fields will add to our understanding of the mechanisms underlying the effects of the HMF.…”

Section: Sequential Changes In Gene Expressionmentioning

confidence: 99%

Transcriptome profile of human neuroblastoma cells in the hypomagnetic field

Liu

Bartlett

et al. 2014

Sci. China Life Sci.

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Research has shown that the hypomagnetic field (HMF) can affect embryo development, cell proliferation, learning and memory, and in vitro tubulin assembly. In the present study, we aimed to elucidate the molecular mechanism by which the HMF exerts its effect, by comparing the transcriptome profiles of human neuroblastoma cells exposed to either the HMF or the geomagnetic field. A total of 2464 differentially expressed genes (DEGs) were identified, 216 of which were up-regulated and 2248 of which were down-regulated after exposure to the HMF. These DEGs were found to be significantly clustered into several key processes, namely macromolecule localization, protein transport, RNA processing, and brain function. Seventeen DEGs were verified by real-time quantitative PCR, and the expression levels of nine of these DEGs were measured every 6 h. Most notably, MAPK1 and CRY2, showed significant up-and down-regulation, respectively, during the first 6 h of HMF exposure, which suggests involvement of the MAPK pathway and cryptochrome in the early bio-HMF response. Our results provide insights into the molecular mechanisms underlying the observed biological effects of the HMF. hypomagnetic field, geomagnetic field, transcriptome profile, massively parallel sequencing, MAPK1, CRY2 Citation:Mo WC, Liu Y, Bartlett PF, He RQ. Transcriptome profile of human neuroblastoma cells in the hypomagnetic field.

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“…Another important signaling mechanism that appears to be influenced by ELF-MF is the elevation of intracellular Ca 2+ in exposed cells [24,25] within 1 min of exposure to ELF-MF at 50 Hz and 0.1 mT. Interestingly, the calcium response, as well as other signaling processes, is elevated upon long-term (> 3 h) ELF-MF exposure as well [26][27][28], but these effects are due to downstream processes rather than to a direct effect of the radiation [29].…”

Section: Introductionmentioning

confidence: 99%

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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The Proliferative Response of NB69 Human Neuroblastoma Cells to a 50 Hz Magnetic Field is mediated by ERK1/2 Signaling

Cited by 37 publications

References 48 publications

Electric Stimulation at 448 kHz Promotes Proliferation of Human Mesenchymal Stem Cells

Electric Stimulation at 448 kHz Promotes Proliferation of Human Mesenchymal Stem Cells

Transcriptome profile of human neuroblastoma cells in the hypomagnetic field

Activation of Signaling Cascades by Weak Extremely Low Frequency Electromagnetic Fields

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