title: L-dopa and dopamine enhance the formation of aggregates under proteasome inhibition in PC12 cells.
abstract: The formation of inclusion bodies in dopaminergic neurons is associated with the pathogenesis of Parkinson's disease. In order to clarify the role of dopamine/L-dopa in the formation of protein aggregates, we investigated dopamine/L-dopa-related aggregation using an experimental inclusion model. The inhibition of tyrosine hydroxylase (TH) by alpha-methyltyrosine dramatically decreased MG132-induced aggregate formation. In addition, the inhibition of TH caused the upregulation of proteasomes in cultured cells and the dopamine/L-dopa induced non-enzymatic polymerization of ubiquitin. This inhibition did not affect cell viability. These results suggest that dopamine/L-dopa might enhance aggregate formation, and that intracellular aggregates may not be toxic to cells.
authors.affiliation: Department of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, 36-1, Nishicho, Yonago 683-8504, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yoshimoto
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nakaso
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakashima
mesh_terms: D000818:Animals; D002401:Cathepsin B / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004298:Dopamine / Q000494:pharmacology*; D007976:Leupeptins / Q000494:pharmacology; D007980:Levodopa / Q000494:pharmacology*; D016716:PC12 Cells; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D051381:Rats; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D019805:alpha-Methyltyrosine / Q000494:pharmacology
chemical_list: D007976:Leupeptins; D061988:Proteasome Inhibitors; D025801:Ubiquitin; D007980:Levodopa; D019805:alpha-Methyltyrosine; D014446:Tyrosine 3-Monooxygenase; D002401:Cathepsin B; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde; D004298:Dopamine