TY - JOUR
T1 - Local proteins associated with methamphetamine-induced nigrostriatal dopaminergic neurotoxicity
AU - Liao, Pao Chi
AU - Kuo, Yu Min
AU - Hsu, Hen Chia
AU - Cherng, Chienfang G.
AU - Yu, Lung
PY - 2005/10
Y1 - 2005/10
N2 - 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, α-synuclein, and four down-regulated proteins, ATPase, F-actin capping protein β subunit, ubiquitin carboxyterminal hydrolase/PGP 9.5, and peroxidase. MA-altered expression levels of α-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 α-synuclein and down-regulation of ubiquitin carboxy-terminal hydrolase/PGP 9.5 could be linked to the MA-induced dopaminergic terminal toxicity.
AB - 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, α-synuclein, and four down-regulated proteins, ATPase, F-actin capping protein β subunit, ubiquitin carboxyterminal hydrolase/PGP 9.5, and peroxidase. MA-altered expression levels of α-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 α-synuclein and down-regulation of ubiquitin carboxy-terminal hydrolase/PGP 9.5 could be linked to the MA-induced dopaminergic terminal toxicity.
KW - Dopamine
KW - Methamphetamine
KW - Neurodegeneration
KW - Neurotoxicity
KW - Proteomics
KW - Striatum
UR - http://www.scopus.com/inward/record.url?scp=25644445316&partnerID=8YFLogxK
U2 - 10.1111/j.1471-4159.2005.03346.x
DO - 10.1111/j.1471-4159.2005.03346.x
M3 - Article
C2 - 16181420
AN - SCOPUS:25644445316
SN - 0022-3042
VL - 95
SP - 160
EP - 168
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 1
ER -