Non-thermal activation of the hsp27/p38MAPK stress pathway by mobile phone radiation in human endothelial cells: molecular mechanism for cancer- and blood-brain barrier-related effects.

Abstract

We have examined whether non-thermal exposures of cultures of the human endothelial cell line EA.hy926 to 900 MHz GSM mobile phone microwave radiation could activate stress response. Results obtained demonstrate that 1-hour non-thermal exposure of EA.hy926 cells changes the phosphorylation status of numerous, yet largely unidentified, proteins. One of the affected proteins was identified as heat shock protein-27 (hsp27). Mobile phone exposure caused a transient increase in phosphorylation of hsp27, an effect which was prevented by SB203580, a specific inhibitor of p38 mitogen-activated protein kinase (p38MAPK). Also, mobile phone exposure caused transient changes in the protein expression levels of hsp27 and p38MAPK. All these changes were non-thermal effects because, as determined using temperature probes, irradiation did not alter the temperature of cell cultures, which remained throughout the irradiation period at 37 +/- 0.3 degrees C. Changes in the overall pattern of protein phosphorylation suggest that mobile phone radiation activates a variety of cellular signal transduction pathways, among them the hsp27/p38MAPK stress response pathway. Based on the known functions of hsp27, we put forward the hypothesis that mobile phone radiation-induced activation of hsp27 may (i) facilitate the development of brain cancer by inhibiting the cytochrome c/caspase-3 apoptotic pathway and (ii) cause an increase in blood-brain barrier permeability through stabilization of endothelial cell stress fibers. We postulate that these events, when occurring repeatedly over a long period of time, might become a health hazard because of the possible accumulation of brain tissue damage. Furthermore, our hypothesis suggests that other brain damaging factors may co-participate in mobile phone radiation-induced effects.

AI evidence extraction

Main findings

A 1-hour non-thermal 900 MHz GSM exposure altered the phosphorylation pattern of multiple proteins in EA.hy926 cells, including a transient increase in hsp27 phosphorylation. The hsp27 phosphorylation increase was prevented by the p38MAPK inhibitor SB203580, and exposure also caused transient changes in hsp27 and p38MAPK protein expression levels; measured culture temperature did not change during irradiation.

Outcomes measured

• Protein phosphorylation changes
• hsp27 phosphorylation
• p38MAPK involvement (SB203580 inhibition)
• hsp27 protein expression level changes
• p38MAPK protein expression level changes
• Temperature change during exposure (non-thermal confirmation)

Limitations

• In vitro cell-line study; findings may not translate to humans or in vivo conditions
• Many affected phosphorylated proteins were described as largely unidentified
• No SAR or detailed dosimetry reported in the abstract
• Health implications (brain cancer, blood-brain barrier permeability) are presented as hypotheses rather than directly measured outcomes

Suggested hubs

• who-icnirp (0.2)
  Mobile phone RF exposure with discussion of potential health relevance; no direct policy content stated.

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    "study_type": "in_vitro",
    "exposure": {
        "band": "RF",
        "source": "mobile phone",
        "frequency_mhz": 900,
        "sar_wkg": null,
        "duration": "1-hour"
    },
    "population": "Human endothelial cell line EA.hy926 (cell culture)",
    "sample_size": null,
    "outcomes": [
        "Protein phosphorylation changes",
        "hsp27 phosphorylation",
        "p38MAPK involvement (SB203580 inhibition)",
        "hsp27 protein expression level changes",
        "p38MAPK protein expression level changes",
        "Temperature change during exposure (non-thermal confirmation)"
    ],
    "main_findings": "A 1-hour non-thermal 900 MHz GSM exposure altered the phosphorylation pattern of multiple proteins in EA.hy926 cells, including a transient increase in hsp27 phosphorylation. The hsp27 phosphorylation increase was prevented by the p38MAPK inhibitor SB203580, and exposure also caused transient changes in hsp27 and p38MAPK protein expression levels; measured culture temperature did not change during irradiation.",
    "effect_direction": "mixed",
    "limitations": [
        "In vitro cell-line study; findings may not translate to humans or in vivo conditions",
        "Many affected phosphorylated proteins were described as largely unidentified",
        "No SAR or detailed dosimetry reported in the abstract",
        "Health implications (brain cancer, blood-brain barrier permeability) are presented as hypotheses rather than directly measured outcomes"
    ],
    "evidence_strength": "low",
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    "peer_reviewed_likely": "yes",
    "keywords": [
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        "GSM",
        "mobile phone radiation",
        "microwave",
        "non-thermal",
        "endothelial cells",
        "EA.hy926",
        "stress response",
        "hsp27",
        "p38MAPK",
        "protein phosphorylation",
        "SB203580"
    ],
    "suggested_hubs": [
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            "reason": "Mobile phone RF exposure with discussion of potential health relevance; no direct policy content stated."
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