title: Extremely Low Frequency Magnetic Field (ELF-MF) Exposure Sensitizes SH-SY5Y Cells to the Pro-Parkinson's Disease Toxin MPP(.).
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.
authors.affiliation: Health Protection Technology Division, ENEA-Casaccia, 00123, Rome, Italy. barbara.benassi@enea.it.
authors.forename: Barbara
authors.initials: B
authors.lastname: Benassi
authors.affiliation: Department of Biology, Tor Vergata University, Rome, Italy.|Danish Cancer Society Research Center, Copenhagen, Denmark.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Filomeni
authors.affiliation: Department of Biology, Tor Vergata University, Rome, Italy.|Danish Cancer Society Research Center, Copenhagen, Denmark.
authors.forename: Costanza
authors.initials: C
authors.lastname: Montagna
authors.affiliation: Health Protection Technology Division, ENEA-Casaccia, 00123, Rome, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Merla
authors.affiliation: Health Protection Technology Division, ENEA-Casaccia, 00123, Rome, Italy.
authors.forename: Vanni
authors.initials: V
authors.lastname: Lopresto
authors.affiliation: Health Protection Technology Division, ENEA-Casaccia, 00123, Rome, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Pinto
authors.affiliation: Health Protection Technology Division, ENEA-Casaccia, 00123, Rome, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Marino
authors.affiliation: Health Protection Technology Division, ENEA-Casaccia, 00123, Rome, Italy. claudia.consales@enea.it.
authors.forename: Claudia
authors.initials: C
authors.lastname: Consales
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D060526:Magnetic Fields; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010300:Parkinson Disease / Q000473:pathology*; D050050:Protein Carbonylation / Q000187:drug effects; D013438:Sulfhydryl Compounds / Q000378:metabolism
chemical_list: D013438:Sulfhydryl Compounds; D015655:1-Methyl-4-phenylpyridinium
keywords: 1-methyl-4-phenylpyridinium (MPP+); Apoptosis; Extremely low frequency magnetic field (ELF-MF); Oxidative stress; Parkinson’s disease (PD); SH-SY5Y