Local proteins associated with methamphetamine-induced nigrostriatal dopaminergic neurotoxicity.

Abstract:

:The present study aimed to examine the proteins involved in the methamphetamine (MA)-induced nigrostriatal dopaminergic toxicity. Infusion of anisomycin into striatum and substantia nigra both abolished the MA-induced striatal dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) depletions, indicating a critical role of local protein synthesis in determining such dopaminergic toxicity. Moreover, local protein synthesis blockade reversed this neurotoxicity via a temperature-independent mechanism. We then employed a proteomic approach, two-dimensional gel electrophoresis (2-DE) in conjunction with mass spectrometry analysis, to identify the protein candidates associated with the MA-induced neurotoxicity. In striatal samples, 2-DE analysis revealed that the intensities of nine protein spots were altered by MA treatment. Mass spectrometry analysis allowed us to identify five proteins, including an up-regulated protein, alpha-synuclein, and four down-regulated proteins, ATPase, F-actin capping protein beta subunit, ubiquitin carboxy-terminal hydrolase/PGP 9.5, and peroxidase. MA-altered expression levels of alpha-synuclein and ubiquitin carboxy-terminal hydrolase/PGP 9.5 in striata were confirmed by western blotting analysis. Taken together, these results suggest that local up-regulation of alpha-synuclein and down-regulation of ubiquitin carboxy-terminal hydrolase/PGP 9.5 could be linked to the MA-induced dopaminergic terminal toxicity.

journal_name

J Neurochem

authors

Liao PC,Kuo YM,Hsu HC,Cherng CG,Yu L

doi

10.1111/j.1471-4159.2005.03346.x

keywords:

subject

Has Abstract

pub_date

2005-10-01 00:00:00

pages

160-8

issue

1

eissn

0022-3042

issn

1471-4159

pii

JNC3346

journal_volume

95

pub_type

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