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Changes in cytoskeletal and mitochondrial proteins in striatum following MPTP lesion in the mouse
Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
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Article in journal (Refereed) Submitted
URN: urn:nbn:se:uu:diva-95434OAI: oai:DiVA.org:uu-95434DiVA: diva2:169634
Available from: 2007-02-09 Created: 2007-02-09Bibliographically approved
In thesis
1. Neuropeptidomics – Expanding Proteomics Downwards
Open this publication in new window or tab >>Neuropeptidomics – Expanding Proteomics Downwards
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Biological function is mainly carried out by a dynamic population of proteins which may be used as markers for disease diagnosis, prognosis, and as a guide for effective treatment. In analogy to genomics, the study of proteins is called proteomics and it is generally performed by two-dimensional gel electrophoresis and mass spectrometric methods. However, gel based proteomics is methodologically restricted from the low mass region which includes important endogenous peptides. Furthermore, the study of endogenous peptides, peptidomics, is compromised by protein fragments produced post mortem during conventional sample handling.

In this thesis nanoflow liquid chromatography and mass spectrometry have been used together with improved methods for sample preparation to semi-quantitatively monitor peptides in brain tissue. The proteolysis of proteins and rise of fragments in the low mass region was studied in a time-course study up to ten minutes, where a potential marker for sample quality was found. When rapidly denatured brain tissue was analyzed, the methods enabled detection of hundreds of peptides and identifications of several endogenous peptides not previously described in the literature. The identification process of endogenous peptides has been improved by creating small targeted sequence collections from existing databases.

In applications of the MPTP model for Parkinson’s disease the protein and peptide expressions were compared to controls. Several proteins were significantly changed belonging to groups of mitochondrial, cytoskeletal, and vesicle associated proteins. In the peptidomic study, the levels of the small protein PEP-19 was found to be significantly decreased in the striatum of MPTP administered animals. Using imaging mass spectrometry the spatial distribution of PEP-19 was found to be predominant in the striatum and the levels were concordantly decreased in the parkinsonian tissue as verified by immunoblotting.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 46 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 48
Pharmaceutical pharmacology, proteomics, peptidomics, mass spectrometry, neuropeptide, chromatography, Farmaceutisk farmakologi
National Category
Pharmaceutical Sciences
urn:nbn:se:uu:diva-7465 (URN)978-91-554-6791-1 (ISBN)
Public defence
2007-03-02, B:42, BMC, Husargatan 3, Uppsala, 10:15 (English)
Available from: 2007-02-09 Created: 2007-02-09 Last updated: 2010-01-15Bibliographically approved

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