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Extremely Low Frequency Magnetic Field (ELF-MF) Exposure Sensitizes SH-SY5Y Cells to the Pro-Parkinson’s Disease Toxin MPP+

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Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuron loss, with an etiopathogenesis involving both genetic and environmental factors. The occupational/residential exposure to the electromagnetic fields has been recently associated with an increased risk of neurodegenerative diseases; it has been thus proposed that the extremely low frequency magnetic field (ELF-MF) may contribute to neurodegenerative etiopathogenesis, as its interaction with biological systems directly impairs redox homeostasis in specific areas of the brain. The molecular mechanisms elicited by ELF-MF, and their potential involvement in PD onset, still remain unclear. To this end, we set up a generator of ELF-MF able to stably and homogeneously reproduce environmental prolonged exposure to ELF-MF (50 Hz, 1 mT). Results obtained indicate that ELF-MF exposure alters cell response of SH-SY5Y cells to MPP+. We demonstrate that ELF-MF does not affect per se survival, shape, and morphology of both proliferating and differentiated SH-SY5Y cells but significantly impairs redox homeostasis and thiol content, triggering an increase in protein carbonylation. As a result, toxicity of MPP+, even at low doses, is highly enhanced in ELF-MF-exposed cells due to a significant increase in ROS levels, potentiation of oxidative damage, and induction of a caspase-dependent apoptosis. Pre-incubation with the thiol antioxidants N-acetyl-l-cysteine and GSH ethyl-ester significantly reduces the extent of oxidative damage and protects cells from death induced by the combined treatment ELF-MF/MPP+. Taken overall, our results demonstrate the redox-based molecular interaction between ELF-MF and PD neurotoxins in vitro, and open a new scenario for defining the synergy of environmental factors in PD onset.

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Abbreviations

AD:

Alzheimer’s disease

ALS:

Amyotrophic lateral sclerosis

B field:

Induction magnetic field

BSO:

Buthionine-S,R-sulfoximine

CMFDA:

5-chloromethylfluorescein diacetate

DAergic:

Dopaminergic

DHE:

Dihydroethidium

E field:

Electric field

ELF-MF:

Extremely low frequency magnetic fields

GSH:

Reduced glutathione

GSHest:

Reduced glutathione ethyl ester

H2-DCFDA:

2′,7′-Dichlorofluorescin diacetate

LBs:

Lewy bodies

MFI:

Mean fluorescence intensity

MPP+ :

1-methyl-4-phenylpyridinium

MPTP:

Methyl-4-phenyl-1,2,3,6-tetra-hydropyridine

NAC:

N-Acetyl-l-cysteine

PD:

Parkinson’s disease

PI:

Propidium iodide

PMA:

Phorbol 12-myristate 13-acetate

RA:

Retinoic acid

RMS:

Root-mean-square

ROS:

Reactive oxygen species

SN:

Substrantia nigra

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Acknowledgments

G.F. is supported by grants from the National Ministry of Health, Young Italian Researcher Grant-2008 (Grant GR-2008-1138121), and from the Italian Association for Cancer Research, AIRC-MFAG 2011 (Grant 11452). We are very grateful to Francesca Pacchierotti for her helpful criticisms and scientific support and to Martin W. Bennett for manuscript editing.

Conflict of Interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Health Protection Technology Division, ENEA-Casaccia, 00123, Rome, Italy

    Barbara Benassi, Caterina Merla, Vanni Lopresto, Rosanna Pinto, Carmela Marino & Claudia Consales

  2. Department of Biology, Tor Vergata University, Rome, Italy

    Giuseppe Filomeni & Costanza Montagna

  3. Danish Cancer Society Research Center, Copenhagen, Denmark

    Giuseppe Filomeni & Costanza Montagna

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  1. Barbara Benassi
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  2. Giuseppe Filomeni
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  3. Costanza Montagna
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Correspondence to Barbara Benassi or Claudia Consales.

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Benassi, B., Filomeni, G., Montagna, C. et al. Extremely Low Frequency Magnetic Field (ELF-MF) Exposure Sensitizes SH-SY5Y Cells to the Pro-Parkinson’s Disease Toxin MPP+ . Mol Neurobiol 53, 4247–4260 (2016). https://doi.org/10.1007/s12035-015-9354-4

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