Activation of Signaling Cascades by Weak Extremely Low Frequency Electromagnetic Fields

2017 · Mixed · Low evidence

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MixedLow evidencePaper 2337

Study snapshot

Publicationmanual · 2017

Study typein_vitro

Reported directionMixed

Evidence ratingLow

Abstract

Activation of Signaling Cascades by Weak Extremely Low Frequency Electromagnetic Fields Kapri-Pardes E, Hanoch T, Maik-Rachline G, Murbach M, Bounds PL, Kuster N, Seger R. Activation of Signaling Cascades by Weak Extremely Low Frequency Electromagnetic Fields. Cell Physiol Biochem. 2017 Oct 16;43(4):1. doi: 10.1159/000481977. Abstract 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. ncbi.nlm.nih.gov

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AI evidence extraction

Structured fields below were generated from the paper’s abstract and metadata to make the evidence easier to inspect. Automated extraction may be incomplete or incorrect; verify important details against the original paper.

Study typein_vitro

Effect directionmixed

PopulationEight different cell types (transformed and non-transformed)

Sample sizeNot supplied

ExposureELF · various time periods

Evidence strengthLowConfidence: 74% · Peer reviewed: yes

Main findings

Across eight cell types, ELF-MF exposure increased ERK1/2 phosphorylation; p38 MAPK was very slightly phosphorylated, while JNK and Akt were not. ERK1/2 phosphorylation was detected at field strengths as low as 0.15 µT and was maximal at approximately 10 µT; the ERK1/2 response was blocked by diphenyleneiodonium, suggesting involvement of NADP oxidase. The authors state the ERK1/2 increase is likely too small to induce ELF-MF-dependent proliferation or oncogenic transformation and is not proof of involvement of ELF-MF in cancer or childhood leukemia.

Outcomes measured

ERK1/2 phosphorylation
p38 MAPK phosphorylation
JNK phosphorylation
Akt phosphorylation
Cell proliferation (inference/assessment)
Oncogenic transformation (inference/assessment)
Effect of diphenyleneiodonium (flavoprotein inhibitor) on ERK1/2 phosphorylation

Limitations

Frequency of ELF-MF not specified in the abstract
Sample sizes/replicates not reported in the abstract
Proliferation/oncogenic transformation were not demonstrated; conclusions about these outcomes are based on the magnitude of signaling changes

View raw extracted JSON

{
  "study_type": "in_vitro",
  "exposure": {
    "band": "ELF",
    "source": null,
    "frequency_mhz": null,
    "sar_wkg": null,
    "duration": "various time periods"
  },
  "population": "Eight different cell types (transformed and non-transformed)",
  "sample_size": null,
  "outcomes": [
    "ERK1/2 phosphorylation",
    "p38 MAPK phosphorylation",
    "JNK phosphorylation",
    "Akt phosphorylation",
    "Cell proliferation (inference/assessment)",
    "Oncogenic transformation (inference/assessment)",
    "Effect of diphenyleneiodonium (flavoprotein inhibitor) on ERK1/2 phosphorylation"
  ],
  "main_findings": "Across eight cell types, ELF-MF exposure increased ERK1/2 phosphorylation; p38 MAPK was very slightly phosphorylated, while JNK and Akt were not. ERK1/2 phosphorylation was detected at field strengths as low as 0.15 µT and was maximal at approximately 10 µT; the ERK1/2 response was blocked by diphenyleneiodonium, suggesting involvement of NADP oxidase. The authors state the ERK1/2 increase is likely too small to induce ELF-MF-dependent proliferation or oncogenic transformation and is not proof of involvement of ELF-MF in cancer or childhood leukemia.",
  "effect_direction": "mixed",
  "limitations": [
    "Frequency of ELF-MF not specified in the abstract",
    "Sample sizes/replicates not reported in the abstract",
    "Proliferation/oncogenic transformation were not demonstrated; conclusions about these outcomes are based on the magnitude of signaling changes"
  ],
  "evidence_strength": "low",
  "confidence": 0.74,
  "peer_reviewed_likely": "yes",
  "keywords": [
    "extremely low frequency magnetic fields",
    "ELF-MF",
    "MAPK",
    "ERK1/2",
    "p38",
    "JNK",
    "Akt",
    "phosphorylation",
    "western blot",
    "NADP oxidase",
    "diphenyleneiodonium",
    "cell signaling"
  ],
  "suggested_hubs": [
    {
      "slug": "occupational-exposure",
      "weight": 0.2,
      "reason": "Study examines ELF magnetic-field strengths in the µT range, which can be relevant to occupational ELF exposures, though no specific source is described."
    }
  ]
}

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AI-extracted fields are generated from the abstract and metadata and may be incomplete or incorrect. This material is for informational purposes and is not medical advice.

Identifiers and source

DOI: 10.1159/000481977
PubMed: Not supplied

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