title: 5-S-cysteinyldopamine neurotoxicity: Influence on the expression of α-synuclein and ERp57 in cellular and animal models of Parkinson's disease.
abstract: Parkinson's disease (PD) is a progressive neurodegenerative disorder whose etiology is still unclear in spite of extensive investigations. It has been hypothesized that 5-S-cysteinyldopamine (CysDA), a catechol-thioether metabolite of dopamine (DA), could be an endogenous parkinsonian neurotoxin. To gain further insight into its role in the neurodegenerative process, both CD1 mice and SH-SY5Y neuroblastoma cells were treated with CysDA, and the data were compared with those obtained by the use of 6-hydroxydopamine, a well-known parkinsonian mimetic. Intrastriatal injection of CysDA in CD1 mice caused a long-lasting depletion of DA, providing evidence of in vivo neurotoxicity of CysDA. Both in mice and in SH-SY5Y cells, CysDA treatment induced extensive oxidative stress, as evidenced by protein carbonylation and glutathione depletion, and affected the expression of two proteins, α-synuclein (α-Syn) and ERp57, whose levels are modulated by oxidative insult. Real-time PCR experiments support these findings, indicating an upregulation of both ERp57 and α-Syn expression. α-Syn aggregation was also found to be modulated by CysDA treatment. The present work provides a solid background sustaining the hypothesis that CysDA is involved in parkinsonian neurodegeneration by inducing extensive oxidative stress and protein aggregation.
authors.affiliation: Department of Biochemical Sciences, "Sapienza" University, Roma, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Aureli
authors.forename: Tommaso
authors.initials: T
authors.lastname: Cassano
authors.forename: Alessandra
authors.initials: A
authors.lastname: Masci
authors.forename: Antonio
authors.initials: A
authors.lastname: Francioso
authors.forename: Sara
authors.initials: S
authors.lastname: Martire
authors.forename: Annalisa
authors.initials: A
authors.lastname: Cocciolo
authors.forename: Silvia
authors.initials: S
authors.lastname: Chichiarelli
authors.forename: Adele
authors.initials: A
authors.lastname: Romano
authors.forename: Silvana
authors.initials: S
authors.lastname: Gaetani
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mancini
authors.forename: Mario
authors.initials: M
authors.lastname: Fontana
authors.forename: Maria
authors.initials: M
authors.lastname: d'Erme
authors.forename: Luciana
authors.initials: L
authors.lastname: Mosca
mesh_terms: D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004298:Dopamine / Q000031:analogs & derivatives* / Q000633:toxicity; D015259:Dopamine Agents / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D009447:Neuroblastoma / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000209:etiology*; D050050:Protein Carbonylation / Q000187:drug effects; D019704:Protein Disulfide-Isomerases / Q000235:genetics / Q000378:metabolism*; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*
chemical_list: D015306:Biogenic Monoamines; D015259:Dopamine Agents; D051844:alpha-Synuclein; D016627:Oxidopamine; C047408:5-S-cysteinyldopamine; C513195:Pdia3 protein, mouse; D019704:Protein Disulfide-Isomerases; D005978:Glutathione; D019803:Glutathione Disulfide; D004298:Dopamine
keywords: 5-S-cysteinyldopamine; 6-hydroxydopamine; ERp57; Parkinson's disease; α-synuclein