Accelerated proteasomal activity induced by Pb2+, Ga3+, or Cu2+ exposure does not induce degradation of alpha-synuclein.
J Environ Pathol Toxicol Oncol
; 28(1): 5-24, 2009.
Article
em En
| MEDLINE
| ID: mdl-19392651
ABSTRACT
The involvement of environmental heavy metals in Parkinson's disease (PD) has been suggested by epidemiologic studies; however, the mechanism of this effect is unknown. PD is characterized by the aggregation of alpha-synuclein in Lewy bodies. We previously showed that Pb2+ accelerates proteasomal activity. Therefore, we examined the effect of Pb2+, Ga3+, and Cu2+ on alpha-synuclein in human SH-SY5Y cells. The heavy metals induced an increase in heme-oxygenase-1 levels without significant cell death or ROS generation. The metals inhibited ALA-dehydratase, which is the inhibitory subunit of the proteasome, thereby accelerating proteasomal activity and decreasing protein levels of CDK-1 and PBGD. However, alpha-synuclein protein levels increased after exposure to metals, similar to the effect obtained with the proteasome inhibitor, hemin, suggesting that alpha-synuclein is inaccessible to proteasomal degradation. Indeed, electron microscopy revealed the formation of aggresomes in Pb2+- or hemin-treated cells. Thus, although heavy metals enhance proteasomal activity, alpha-synuclein is protected from degradation, and its protein levels and aggregation are increased.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cobre
/
Complexo de Endopeptidases do Proteassoma
/
Alfa-Sinucleína
/
Gálio
/
Chumbo
Limite:
Humans
Idioma:
En
Revista:
J Environ Pathol Toxicol Oncol
Assunto da revista:
NEOPLASIAS
/
PATOLOGIA
/
SAUDE AMBIENTAL
/
TOXICOLOGIA
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Israel