Decreased striatal levels of PEP-19 following MPTP lesion in the mouse.
PEP-19 is a neuronal calmodulin-binding protein, and as such, a putative modulator of calcium regulated processes. In the present study, we used proteomics technology approaches such as peptidomics and imaging MALDI mass spectrometry, as well as traditional techniques (immunoblotting and in situ hybridization) to identify PEP-19 and, specifically, to measure PEP-19 mRNA and protein levels in an animal model of Parkinson's disease. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration in mice resulted in a significant decrease in striatal PEP-19 mRNA. Capillary nano-flow liquid chromatography electrospray mass spectrometry analysis of striatal tissue revealed a significant decrease of the PEP-19 protein level. Moreover, imaging MALDI mass spectrometry also showed that PEP-19 protein was predominantly localized to the striatum of the brain tissue cross sections. After MPTP administration, PEP-19 levels were significantly reduced by 30%. We conclude that PEP-19 mRNA and protein expression are decreased in the striatum of a common animal model of Parkinson's disease. Further studies are needed to show the specific involvement of PEP-19 in the neurodegeneration seen in MPTP lesioned animals. Finally, this study has shown that the combination of traditional molecular biology techniques with novel, highly specific and sensitive mass spectrometry methods is advantageous in characterizing molecular events of many diseases, including Parkinson's disease.
Sköld
Karl
K
Laboratory for Biological and Medical Mass Spectrometry, Uppsala University, Box 583 Biomedical Centre, SE-75123 Uppsala, Sweden.
Svensson
Marcus
M
Nilsson
Anna
A
Zhang
Xiaoqun
X
Nydahl
Katarina
K
Caprioli
Richard M
RM
Svenningsson
Per
P
Andrén
Per E
PE
D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology; D017403:In Situ Hybridization; D020267:MPTP Poisoning / Q000150:complications; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D009419:Nerve Tissue Proteins; C489091:Pcp4 protein, mouse; D010455:Peptides; D012333:RNA, Messenger