Proteomic analysis of striatal proteins in the rat model of L-DOPA-induced dyskinesia.
L-DOPA-induced dyskinesia (LID) is among the motor complications that arise in Parkinson's disease (PD) patients after a prolonged treatment with L-DOPA. To this day, transcriptome analysis has been performed in a rat model of LID [Neurobiol. Dis., 17 (2004), 219] but information regarding the proteome is still lacking. In the present study, we investigated the changes occurring at the protein level in striatal samples obtained from the unilaterally 6-hydroxydopamine-lesion rat model of PD treated with saline, L-DOPA or bromocriptine using two-dimensional difference gel electrophoresis and mass spectrometry (MS). Rats treated with L-DOPA were allocated to two groups based on the presence or absence of LID. Among the 2000 spots compared for statistical difference, 67 spots were significantly changed in abundance and identified using matrix-assisted laser desorption/ionization time-of-flight MS, atmospheric pressure matrix-assisted laser desorption/ionization and HPLC coupled tandem MS (LC/MS/MS). Out of these 67 proteins, LID significantly changed the expression level of five proteins: alphabeta-crystalin, gamma-enolase, guanidoacetate methyltransferase, vinculin, and proteasome alpha-2 subunit. Complementary techniques such as western immunoblotting and immunohistochemistry were performed to investigate the validity of the data obtained using the proteomic approach. In conclusion, this study provides new insights into the protein changes occurring in LID.
Valastro
Barbara
B
Basal Ganglia Pathophysiology Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden. barbara.valastro@merz.de
Dekundy
Andrzej
A
Krogh
Morten
M
Lundblad
Martin
M
James
Peter
P
Danysz
Wojciech
W
Quack
Guenter
G
Cenci
Maria Angela
MA
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D003342:Corpus Striatum / Q000378:metabolism*; D004195:Disease Models, Animal; D004409:Dyskinesia, Drug-Induced / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D007980:Levodopa / Q000009:adverse effects*; D008297:Male; D013058:Mass Spectrometry; D011506:Proteins / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D011506:Proteins; D007980:Levodopa