Magnetic field-induced Ca 2+ intake by mesenchymal stem cells is mediated by intracellular Zn 2+ and accompanied by a Zn 2+ influx

Abstract

Magnetic field-induced Ca 2+ intake by mesenchymal stem cells is mediated by intracellular Zn 2+ and accompanied by a Zn 2+ influx Alp Özgün, Bora Garipcan. Magnetic field-induced Ca 2+ intake by mesenchymal stem cells is mediated by intracellular Zn 2+ and accompanied by a Zn 2+ influx. Biochim Biophys Acta Mol Cell Res. 2021 May 22;119062. doi: 10.1016/j.bbamcr.2021.119062. Highlights • Magnetic field-induced oxidative stress is not derived from mitochondrial activity. • Ca2+ intake under magnetic field exposure is accompanied by Zn2+ intake. • Magnetic field-evoked cation intake depends on availability of intracellular Zn2+. • 2-APB-sensitive pathways are major gateways for cation influx induced by magnetic fields. Abstract Chronic exposure to magnetic fields (MFs) has a diverse range of effects on biological systems but definitive molecular mechanisms of the interaction remain largely unknown. One of the most frequently reported effects of MF exposure is an elevated concentration of intracellular Ca2+ through disputed pathways. Other prominent effects include increased oxidative stress and upregulation of neural markers through EGFR activation in stem cells. Further characterization of cascades triggered by MF exposure is hindered by the phenotype diversity of biological models used in the literature. In an attempt to reveal more mechanistic data in this field, we combined the most commonly used biological model and MF parameters with the most commonly reported effects of MFs. Based on clues from the pathways previously defined as sensitive to MFs (EGFR and Zn2+-binding enzymes), the roles of different types of channels (voltage gated Ca2+ channels, NMDA receptors, TRP channels) were inquired in the effects of 50 Hz MFs on bone marrow-derived mesenchymal stem cells. We report that, an influx of Zn2+ accompanies MF-induced Ca2+ intake, which is only attenuated by the broad-range inhibitor of TRP channels and store-operated Ca2+ entry (SOCE), 2-Aminoethoxydiphenyl borate (2-APB) among other blockers (memantine, nifedipine, ethosuximide and gabapentin). Interestingly, cation influx completely disappears when intracellular Zn2+ is chelated. Our results rule out voltage gated Ca2+ channels as a gateway to MF-induced Ca2+ intake and suggest Zn2+-related channels as a new focus in the field. pubmed.ncbi.nlm.nih.gov

AI evidence extraction

Main findings

In bone marrow-derived mesenchymal stem cells exposed to 50 Hz magnetic fields, Ca2+ intake was accompanied by Zn2+ influx and depended on the availability of intracellular Zn2+. The MF-induced cation influx was attenuated by 2-APB (a broad-range inhibitor of TRP channels and store-operated Ca2+ entry) but not by several other blockers, and it disappeared when intracellular Zn2+ was chelated; the authors report these results rule out voltage-gated Ca2+ channels as the gateway for MF-induced Ca2+ intake.

Outcomes measured

• Intracellular Ca2+ concentration / Ca2+ influx
• Zn2+ influx / intracellular Zn2+ availability
• Oxidative stress (not derived from mitochondrial activity)
• Channel/pathway involvement (TRP channels, SOCE; voltage-gated Ca2+ channels; NMDA receptors)

Limitations

• No magnetic field intensity/flux density reported in the abstract
• No exposure duration details beyond 'chronic exposure'
• In vitro model; generalizability to humans/animals not addressed in abstract
• Sample size and statistical details not provided in abstract

Suggested hubs

• mechanisms-in-vitro (0.9)
  Mechanistic in vitro study of ELF magnetic field effects on ion influx pathways in stem cells.

{
    "study_type": "in_vitro",
    "exposure": {
        "band": "ELF",
        "source": null,
        "frequency_mhz": 0.05000000000000000277555756156289135105907917022705078125,
        "sar_wkg": null,
        "duration": "chronic"
    },
    "population": "Bone marrow-derived mesenchymal stem cells",
    "sample_size": null,
    "outcomes": [
        "Intracellular Ca2+ concentration / Ca2+ influx",
        "Zn2+ influx / intracellular Zn2+ availability",
        "Oxidative stress (not derived from mitochondrial activity)",
        "Channel/pathway involvement (TRP channels, SOCE; voltage-gated Ca2+ channels; NMDA receptors)"
    ],
    "main_findings": "In bone marrow-derived mesenchymal stem cells exposed to 50 Hz magnetic fields, Ca2+ intake was accompanied by Zn2+ influx and depended on the availability of intracellular Zn2+. The MF-induced cation influx was attenuated by 2-APB (a broad-range inhibitor of TRP channels and store-operated Ca2+ entry) but not by several other blockers, and it disappeared when intracellular Zn2+ was chelated; the authors report these results rule out voltage-gated Ca2+ channels as the gateway for MF-induced Ca2+ intake.",
    "effect_direction": "mixed",
    "limitations": [
        "No magnetic field intensity/flux density reported in the abstract",
        "No exposure duration details beyond 'chronic exposure'",
        "In vitro model; generalizability to humans/animals not addressed in abstract",
        "Sample size and statistical details not provided in abstract"
    ],
    "evidence_strength": "low",
    "confidence": 0.7399999999999999911182158029987476766109466552734375,
    "peer_reviewed_likely": "yes",
    "keywords": [
        "50 Hz",
        "extremely low frequency",
        "magnetic fields",
        "mesenchymal stem cells",
        "Ca2+ influx",
        "Zn2+ influx",
        "TRP channels",
        "store-operated calcium entry",
        "2-APB",
        "oxidative stress"
    ],
    "suggested_hubs": [
        {
            "slug": "mechanisms-in-vitro",
            "weight": 0.90000000000000002220446049250313080847263336181640625,
            "reason": "Mechanistic in vitro study of ELF magnetic field effects on ion influx pathways in stem cells."
        }
    ]
}

Comments

Log in to comment.

No comments yet.