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 α-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.

Abbreviations: DMEM, Dulbecco’s Modified Eagle Medium, SDS, sodium dodecyl sulfate, PMSF, phenylmethylsulfonyl fluoride, EDTA, ethylenediaminetetraacetic acid, CBB, coomassie brilliant blue

Keywords: Protein aggregation, Parkinson’s disease, Lewy body, Dopamine metabolism, Ubiquitin-proteasome system