title: Quinoprotein adducts accumulate in the substantia nigra of aged rats and correlate with dopamine-induced toxicity in SH-SY5Y cells.
abstract: Parkinson's disease (PD) is an age-dependent neurodegenerative disorder characterized by dopaminergic neuron loss in substantia nigra. Previous studies have implicated a role of dopamine oxidation in PD. Dopamine oxidation leads to the formation of dopamine quinone, which generates reactive oxygen species and covalently modifies cysteinyl proteins to form quinoprotein adduct. We compared quinoprotein adduct formation and lipid peroxidation in different brain regions of young and old rats. We found a prominent age-dependent accumulation of quinoprotein adducts in the substantia nigra, while no significant change of lipid peroxidation was detected in any brain regions of 2- to 15-month old rats. To determine whether quinoprotein adduct formation correlates with dopamine-induced cytotoxicity, we analyzed dopamine treated SH-SY5Y cells and found a strong correlation between quinoprotein adduct formation and cytotoxicity. Together, our results indicate that quinoprotein adduct formation may play a role in the age-dependent selective vulnerability of dopaminergic neurons in PD.
authors.affiliation: School of Life Science, East China Normal University, Zhongshan bei lu 3663, Shanghai 200062, China.
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Guohua
authors.initials: G
authors.lastname: Yu
authors.forename: Chonggang
authors.initials: C
authors.lastname: Yuan
authors.forename: Jiyan
authors.initials: J
authors.lastname: Ma
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism; D004298:Dopamine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity*; D018492:Dopamine Antagonists / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000502:physiology; D006801:Humans; D006873:Hydroquinones / Q000378:metabolism*; D017879:Isothiocyanates; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D018492:Dopamine Antagonists; D006873:Hydroquinones; D017879:Isothiocyanates; D009419:Nerve Tissue Proteins; D013454:Sulfoxides; D013861:Thiocyanates; C104705:dopamine quinone; C016766:sulforaphane; D003545:Cysteine; D004298:Dopamine