Evidence of plasma membrane-mediated ROS generation upon ELF exposure in neuroblastoma cells

Abstract

Evidence of plasma membrane-mediated ROS generation upon ELF exposure in neuroblastoma cells Merla C, Liberti M, Consales C, Denzi A, Apollonio F, Marino C, Benassi B. Evidences of plasma membrane- mediated ROS generation upon ELF exposure in neuroblastoma cells. Biochim Biophys Acta Biomembr. 2019 Jun 11. pii: S0005-2736(19)30137-3. doi: 10.1016/j.bbamem.2019.06.005. Abstract BACKGROUND: Molecular mechanisms of interaction between cells and extremely low frequency magnetic fields (ELF-MFs) still represent a matter of scientific debate. In this paper, to identify the possible primary source of oxidative stress induced by ELF-MF in SH-SY5Y human neuroblastoma cells, we estimated the induced electric field and current density at the cell level. METHODS: We followed a computational multiscale approach, estimating the local electric field and current density from the whole sample down to the single cell level. The procedure takes into account morphological modeling of SH-SY5Y cells, arranged in different topologies. Experimental validation has been carried out: neuroblastoma cells have been treated with Diphenyleneiodonium (DPI) -an inhibitor of the plasma membrane enzyme NADPH oxidase (Nox)- administered 24 h before exposure to 50 Hz (1 mT) MF. RESULTS: Macroscopic and microscopic dosimetric evaluations suggest that increased current densities are induced at the plasma membrane/extra-cellular medium interface; identifying the plasma membrane as the main site of the ELF-neuroblastoma cell interaction. The in vitro results provide an experimental proof that plasma membrane Nox exerts a key role in the redox imbalance elicited by ELF, as DPI treatment reverts the generation of reactive oxygen species induced by ELF exposure. GENERAL SIGNIFICANCE: Microscopic current densities induced at the plasma membrane are likely to play an active physical role in eliciting ELF effects related to redox imbalance. Multiscale computational dosimetry, supported by an in vitro approach for validation, is proposed as the innovative and rigorous paradigm to unveil mechanisms underlying the complex ELF-MF interactions. ncbi.nlm.nih.gov

AI evidence extraction

Main findings

Computational multiscale dosimetry suggested increased current densities at the plasma membrane/extracellular medium interface, implicating the plasma membrane as a main interaction site. In vitro, ELF exposure (50 Hz, 1 mT) induced ROS generation, and pretreatment with DPI (a Nox inhibitor) reverted the ELF-induced ROS generation, supporting a role for plasma membrane Nox in the observed redox imbalance.

Outcomes measured

• Reactive oxygen species (ROS) generation
• Redox imbalance/oxidative stress
• Induced electric field and current density at cell level
• Role of plasma membrane NADPH oxidase (Nox) in ELF response

Limitations

• Exposure duration not reported in abstract
• Sample size not reported in abstract
• In vitro neuroblastoma cell model; generalizability to humans not addressed in abstract
• Computational modeling details and uncertainty not fully described in abstract

Suggested hubs

• mechanisms-oxidative-stress (0.9)
  Focus on ELF-induced ROS/redox imbalance and Nox-mediated mechanism at the plasma membrane.

{
    "study_type": "in_vitro",
    "exposure": {
        "band": "ELF",
        "source": null,
        "frequency_mhz": 0.05000000000000000277555756156289135105907917022705078125,
        "sar_wkg": null,
        "duration": null
    },
    "population": "SH-SY5Y human neuroblastoma cells",
    "sample_size": null,
    "outcomes": [
        "Reactive oxygen species (ROS) generation",
        "Redox imbalance/oxidative stress",
        "Induced electric field and current density at cell level",
        "Role of plasma membrane NADPH oxidase (Nox) in ELF response"
    ],
    "main_findings": "Computational multiscale dosimetry suggested increased current densities at the plasma membrane/extracellular medium interface, implicating the plasma membrane as a main interaction site. In vitro, ELF exposure (50 Hz, 1 mT) induced ROS generation, and pretreatment with DPI (a Nox inhibitor) reverted the ELF-induced ROS generation, supporting a role for plasma membrane Nox in the observed redox imbalance.",
    "effect_direction": "harm",
    "limitations": [
        "Exposure duration not reported in abstract",
        "Sample size not reported in abstract",
        "In vitro neuroblastoma cell model; generalizability to humans not addressed in abstract",
        "Computational modeling details and uncertainty not fully described in abstract"
    ],
    "evidence_strength": "low",
    "confidence": 0.7800000000000000266453525910037569701671600341796875,
    "peer_reviewed_likely": "yes",
    "keywords": [
        "ELF-MF",
        "50 Hz",
        "1 mT",
        "SH-SY5Y",
        "neuroblastoma",
        "ROS",
        "oxidative stress",
        "NADPH oxidase",
        "Nox",
        "DPI",
        "computational dosimetry",
        "plasma membrane",
        "current density"
    ],
    "suggested_hubs": [
        {
            "slug": "mechanisms-oxidative-stress",
            "weight": 0.90000000000000002220446049250313080847263336181640625,
            "reason": "Focus on ELF-induced ROS/redox imbalance and Nox-mediated mechanism at the plasma membrane."
        }
    ]
}

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