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Page de résumé pour ULgetd-05192008-200828

Auteur : Motte dit Falisse, Nandini
E-mail de l'auteur : nfalisse@gmail.com
URN : ULgetd-05192008-200828
Langue : Anglais/English
Titre : Relation between the expression of prion protein and the cellular response to oxidative stress: a biological and proteomic approach
Intitulé du diplôme : Doctorat en sciences biomédicales et pharmaceutiques
Département : Médecine - Département des sciences précliniques
Jury :
Nom : Titre :
Charlier, Corinne Membre du jury/Committee Member
De Pauw, Marie-Claire Membre du jury/Committee Member
HEINEN , Ernst Membre du jury/Committee Member
Heinen, Ernst Membre du jury/Committee Member
Montrasio, Fabio Membre du jury/Committee Member
Toussaint, Olivier Membre du jury/Committee Member
Seutin, Vincent Président du jury/Committee Chair
Zorzi, Willy Promoteur/Director
Mots-clés :
  • Transmissible spongiform encephalopathies/Encéphalopathies spongiformes transmissibles
  • Bacillus subtilis/Bacillus subtilis
  • 2DLC/2DLC
  • oxidative stress/stress oxydant
  • neurodegenerative disease/maladies neurodégénératives
Date de soutenance : 2008-04-07
Type d'accès : Restreint/Intranet
Résumé :

Several functions have been attributed to the cellular prion protein, PrPc, amongst which its anti-oxidant role has rapidly been gaining interest in the recent years. We and others have previously shown, that PrPc expressing cells, of neuroblastoma or epithelial origin, seem to exhibit a higher overall viability towards paraquat toxicity than cells expressing basal or low levels of the protein. Although several studies propose a protective mechanism that involves PrPc dependent activation of the superoxide dismutase (SOD) enzymatic machinery or an activation of its own intrinsic antioxidant function, others argue against this SOD-like role. Our objective was to investigate, at a biological and proteomic level, by which potential mechanism PrPc could protect neuroblastoma cells against paraquat induced oxidative damage.

Using a biological aproach, we firstly evaluated the status of the Cu/Zn-SOD enzyme in Human neuroblastoma cells expressing different forms of PrPc following their exposure to paraquat. Next, we performed a proteomic study to investigate by which other potential mechanism(s), PrPc could protect the cell against paraquat induced oxidative stress. Our proteomic approach made use of an optimised two-dimensional liquid chromatography system, the ProteomeLab PF-2D, and reverse phase chromatography coupled with lava purple stained SDS-PAGE, both interfaced with tandem mass spectrometry.

An interesting aspect of our study has been the development of an original immunoproteomic technique called immuno-PF2D-MS/MS, coupling classical immunological methods to a two-dimensional liquid chromatography proteomic tool interfaced with tandem mass spectrometry. We have proposed this technique for antigenic and serological characterization that have important implications in the study of biomarkers. Another important aspect of our study has been the detection of several candidates that could participate in PrPc-mediated protection against paraquat induced oxidative stress. Although, it was out of our scope to investigate each of these candidates in the present study, it presents an interesting perspective for future studies. We have, however, shown the implication of one such candidate: PARP-1. Complimentary tests will be necessary in the future to confirm the actual interaction of this candidate with PrPc.

Autre version :
Fichiers :
Nom du fichier Taille Temps de chargement évalué (HH:MI:SS)
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[Restreint/Intranet] A1.pdf 9.52 Mb 00:22:39 00:00:50
[Restreint/Intranet] cover2.doc 26.11 Kb 00:00:03 < 00:00:01
[Restreint/Intranet] cover3.jpg 529.48 Kb 00:01:15 00:00:02
[Restreint/Intranet] front-cover.jpg 861.75 Kb 00:02:03 00:00:04
[Restreint/Intranet] Remerciements.doc 33.79 Kb 00:00:04 < 00:00:01
[Restreint/Intranet] thesis.pdf 2.94 Mb 00:06:59 00:00:15
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