Decreased striatal levels of PEP-19 following MPTP lesion in the mouse

J Proteome Res. 2006 Feb;5(2):262-9. doi: 10.1021/pr050281f.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Corpus Striatum / metabolism*
  • Corpus Striatum / pathology
  • In Situ Hybridization
  • MPTP Poisoning / complications
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nerve Degeneration / pathology
  • Nerve Tissue Proteins / metabolism*
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / metabolism*
  • Parkinsonian Disorders / pathology
  • Peptides / metabolism*
  • RNA, Messenger / metabolism*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • Nerve Tissue Proteins
  • Pcp4 protein, mouse
  • Peptides
  • RNA, Messenger