Coordinated effects of electromagnetic field exposure on erythropoietin-induced activities of phosphatidylinositol-phospholipase C and phosphatidylinositol 3-kinase.

Abstract

Initial studies with the erythropoietin-sensitive human hematopoietic cell line, TF1, demonstrated both multifarious effects of pulsed electromagnetic field (EMF) exposure on lipid signal transduction and antiproliferative effects of EMF. Stimulation of TF1 cells with erythropoietin resulted in increased phosphatidylinositol 3-kinase activity within 2 min. Addition of wortmannin, an inhibitor of phosphatidylinositol 3-kinase, produced a decrease in cell proliferation as measured by accumulation of cells in the G0/G1 phase of the cell cycle and suppression of erythropoietin-induced DNA synthesis. Similar effects on cell proliferation were seen under EMF treatment. Phosphatidylinositol 3-kinase activity in erythropoietin-stimulated TF1 cells, measured in whole-cell extracts, increased 34% within 2 min and remained above basal levels for at least 20 min. EMF decreased erythropoietin-stimulated phosphatidylinositol 3-kinase activity to lower than basal levels. Additionally, translocation of the 85-kDa regulatory subunit (p85) of phosphatidylinositol 3-kinase to the membrane was prevented by EMF. Phosphatidylinositol-specific phospholipase C was activated, as reflected by increases in diacylglycerol and inositol trisphosphate at 15-60 s after EMF treatment. These results provide the first evidence of subtle coordinated changes by EMF associated with loss of phosphatidylinositol 3-kinase activity, inhibition of the translocation of p85 to the membrane, and activation of phosphatidylinositol-phospholipase C.

AI evidence extraction

Main findings

In erythropoietin-stimulated TF1 cells, PI3K activity increased (reported 34% within 2 min) and remained above basal for at least 20 min; pulsed EMF exposure decreased erythropoietin-stimulated PI3K activity to below basal levels and prevented membrane translocation of the p85 subunit. EMF exposure was also associated with activation of phosphatidylinositol-specific phospholipase C, reflected by increases in DAG and IP3 at 15–60 s after EMF treatment, and produced antiproliferative effects similar to those seen with the PI3K inhibitor wortmannin (G0/G1 accumulation and suppression of erythropoietin-induced DNA synthesis).

Outcomes measured

• Phosphatidylinositol 3-kinase (PI3K) activity
• Cell proliferation/cell cycle distribution (G0/G1 accumulation)
• Erythropoietin-induced DNA synthesis
• Translocation of PI3K regulatory subunit p85 to membrane
• Phosphatidylinositol-specific phospholipase C (PI-PLC) activation
• Diacylglycerol (DAG) levels
• Inositol trisphosphate (IP3) levels

Limitations

• No EMF exposure parameters (e.g., frequency, field strength, waveform details, duration) are provided in the abstract.
• Sample size and replication details are not reported in the abstract.
• In vitro cell-line model; generalizability to in vivo or human health outcomes is not addressed in the abstract.

Suggested hubs

• mechanisms-in-vitro (0.9)
  In vitro study examining EMF effects on intracellular signaling pathways (PI3K, PI-PLC) and proliferation in a human cell line.

{
    "study_type": "in_vitro",
    "exposure": {
        "band": "unknown",
        "source": "pulsed electromagnetic field (EMF)",
        "frequency_mhz": null,
        "sar_wkg": null,
        "duration": null
    },
    "population": "Erythropoietin-sensitive human hematopoietic cell line TF1",
    "sample_size": null,
    "outcomes": [
        "Phosphatidylinositol 3-kinase (PI3K) activity",
        "Cell proliferation/cell cycle distribution (G0/G1 accumulation)",
        "Erythropoietin-induced DNA synthesis",
        "Translocation of PI3K regulatory subunit p85 to membrane",
        "Phosphatidylinositol-specific phospholipase C (PI-PLC) activation",
        "Diacylglycerol (DAG) levels",
        "Inositol trisphosphate (IP3) levels"
    ],
    "main_findings": "In erythropoietin-stimulated TF1 cells, PI3K activity increased (reported 34% within 2 min) and remained above basal for at least 20 min; pulsed EMF exposure decreased erythropoietin-stimulated PI3K activity to below basal levels and prevented membrane translocation of the p85 subunit. EMF exposure was also associated with activation of phosphatidylinositol-specific phospholipase C, reflected by increases in DAG and IP3 at 15–60 s after EMF treatment, and produced antiproliferative effects similar to those seen with the PI3K inhibitor wortmannin (G0/G1 accumulation and suppression of erythropoietin-induced DNA synthesis).",
    "effect_direction": "mixed",
    "limitations": [
        "No EMF exposure parameters (e.g., frequency, field strength, waveform details, duration) are provided in the abstract.",
        "Sample size and replication details are not reported in the abstract.",
        "In vitro cell-line model; generalizability to in vivo or human health outcomes is not addressed in the abstract."
    ],
    "evidence_strength": "low",
    "confidence": 0.7399999999999999911182158029987476766109466552734375,
    "peer_reviewed_likely": "yes",
    "keywords": [
        "pulsed electromagnetic field",
        "EMF",
        "erythropoietin",
        "TF1 cells",
        "phosphatidylinositol 3-kinase",
        "PI3K",
        "p85 translocation",
        "phosphatidylinositol-phospholipase C",
        "diacylglycerol",
        "inositol trisphosphate",
        "cell proliferation",
        "DNA synthesis"
    ],
    "suggested_hubs": [
        {
            "slug": "mechanisms-in-vitro",
            "weight": 0.90000000000000002220446049250313080847263336181640625,
            "reason": "In vitro study examining EMF effects on intracellular signaling pathways (PI3K, PI-PLC) and proliferation in a human cell line."
        }
    ]
}

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