title: Specific pesticide-dependent increases in α-synuclein levels in human neuroblastoma (SH-SY5Y) and melanoma (SK-MEL-2) cell lines.
abstract: Epidemiological studies indicate a role of genetic and environmental factors in Parkinson's disease involving alterations of the neuronal α-synuclein (α-syn) protein. In particular, a relationship between Parkinson's disease and occupational exposure to pesticides has been repeatedly suggested. Our objective was to precisely assess changes in α-syn levels in human neuroblastoma (SH-SY5Y) and melanoma (SK-MEL-2) cell lines following acute exposure to pesticides (rotenone, paraquat, maneb, and glyphosate) using Western blot and flow cytometry. These human cell lines express α-syn endogenously, and overexpression of α-syn (wild type or mutated A53T) can be obtained following recombinant adenoviral transduction. We found that endogenous α-syn levels in the SH-SY5Y neuroblastoma cell line were markedly increased by paraquat, and to a lesser extent by rotenone and maneb, but not by glyphosate. Rotenone also clearly increased endogenous α-syn levels in the SK-MEL-2 melanoma cell line. In the SH-SY5Y cell line, similar differences were observed in the α-syn adenovirus-transduced cells, with a higher increase of the A53T mutated protein. Paraquat markedly increased α-syn in the SK-MEL-2 adenovirus-transduced cell line, similarly for the wild-type or A53T proteins. The observed differences in the propensities of pesticides to increase α-syn levels are in agreement with numerous reports that indicate a potential role of exposure to certain pesticides in the development of Parkinson's disease. Our data support the hypothesis that pesticides can trigger some molecular events involved in this disease and also in malignant melanoma that consistently shows a significant but still unexplained association with Parkinson's disease.
authors.affiliation: Agence Nationale de Sécurité Sanitaire de l'Alimentation, de l'Environnement et du Travail (Anses), Unité Maladies Neuro-Dégénératives, 69394 Lyon Cedex 07, France.
authors.forename: Areski
authors.initials: A
authors.lastname: Chorfa
authors.forename: Dominique
authors.initials: D
authors.lastname: Bétemps
authors.forename: Eric
authors.initials: E
authors.lastname: Morignat
authors.forename: Corinne
authors.initials: C
authors.lastname: Lazizzera
authors.forename: Kevin
authors.initials: K
authors.lastname: Hogeveen
authors.forename: Thibault
authors.initials: T
authors.lastname: Andrieu
authors.forename: Thierry
authors.initials: T
authors.lastname: Baron
mesh_terms: D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005998:Glycine / Q000031:analogs & derivatives / Q000633:toxicity; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D008344:Maneb / Q000633:toxicity; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism; D010269:Paraquat / Q000633:toxicity; D010300:Parkinson Disease / Q000209:etiology; D012402:Rotenone / Q000633:toxicity*; D014161:Transduction, Genetic; D051844:alpha-Synuclein / Q000378:metabolism*; D000097797:Glyphosate
chemical_list: D005998:Glycine; D007306:Insecticides; D008344:Maneb; D010269:Paraquat; D012402:Rotenone; D051844:alpha-Synuclein; D000097797:Glyphosate
keywords: Parkinson’s disease; malignant melanona.; neuroblastoma; pesticides; α-synuclein