L-dopa and dopamine enhance the formation of aggregates under proteasome inhibition in PC12 cells.
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.
Yoshimoto
Yuko
Y
Department of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, 36-1, Nishicho, Yonago 683-8504, Japan.
Nakaso
Kazuhiro
K
Nakashima
Kenji
K
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
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