Molecular profiling of experimental Parkinson's disease: direct analysis of peptides and proteins on brain tissue sections by MALDI mass spectrometry.
Direct molecular profiling of biological samples using matrix-assisted laser desorption ionization mass spectrometry is a powerful tool for identifying phenotypic markers. In this report, protein profiling was used for the first time to generate peptide and protein profiles of brain tissue sections obtained from experimental Parkinson's disease (unilaterally 6-hydroxydopamine treated rats). The mass spectrometer was used to map the peptide and protein expression directly on 12 microm tissue sections in mass-to-charge (m/z) values, providing the capability of mapping specific molecules of the original sample, that is, localization, intensity and m/z ratio. Several protein expression profile differences were found in the dopamine depleted side of the brain when compared to the corresponding intact side, for example, calmodulin, cytochrome c, and cytochrome c oxidase. An increased ratio of post-translational modifications such as acetylations were found in the striatum of proteins in the dopamine depleted side of the brain. These modifications were decreased after subchronic administration of L-Dopa. The present study shows that unique protein profiles can be obtained in specific brain regions (and subregions) directly on brain tissue sections and allows for the study of complex biochemical processes such as those occurring in experimental Parkinson's disease.
Pierson
Johan
J
Laboratory for Biological and Medical Mass Spectrometry, Uppsala University, Box 583 Biomedicum, SE-75123, Sweden.
Norris
Jeremy L
JL
Aerni
Hans-Rudolf
HR
Svenningsson
Per
P
Caprioli
Richard M
RM
Andrén
Per E
PE
D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D007477:Ions; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D016627:Oxidopamine / Q000494:pharmacology; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry*; D010641:Phenotype; D011499:Protein Processing, Post-Translational; D051381:Rats; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
D018663:Adrenergic Agents; D000978:Antiparkinson Agents; D002147:Calmodulin; D007477:Ions; D010455:Peptides; D007980:Levodopa; D016627:Oxidopamine; D045304:Cytochromes c; D003576:Electron Transport Complex IV; D004298:Dopamine