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Coenzyme Q and protein/lipid oxidation in a BSE-infected transgenic mouse model.

Abstract
Oxidative stress and antioxidants play an important role in neurodegenerative diseases. However, the exact participation of antioxidants in the evolution of prion diseases is still largely unknown. The aim of this study was to assess brain levels of coenzyme Q (CoQ), an endogenous lipophilic antioxidant, and the antioxidant/pro-oxidant status by determining oxidative damage to proteins and lipids after intracerebral bovine spongiform encephalopathy (BSE) infection of transgenic mice expressing bovine prion protein (PrP). Our results indicate that, whereas the ratio between the two CoQ homologues present in mice (CoQ(9) and CoQ(10)) is not altered by prion infection during the course of the disease, significant increases in total CoQ(9) and CoQ(10) were observed in BSE-infected mice 150 days after inoculation. This time point coincided with the first manifestation of PrP(Sc) deposition in nervous tissue. In addition, CoQ(9) and CoQ(10) levels, neuropathological alterations, and PrP(Sc) deposition in nervous tissues underwent further increases as the illness progressed. Lipid and protein oxidation were observed only at the final stage of the disease after clinical signs had appeared. These findings indicate upregulation of CoQ(9)- and CoQ(10)-dependent antioxidant systems in response to the increased oxidative stress induced by prion infection in nervous tissue. However, the induction of these endogenous antioxidant systems seems to be insufficient to prevent the development of the illness.
AuthorsSergio F Martin, Isabel Burón, Juan C Espinosa, Joaquín Castilla, José M Villalba, Juan M Torres
JournalFree radical biology & medicine (Free Radic Biol Med) Vol. 42 Issue 11 Pg. 1723-9 (Jun 01 2007) ISSN: 0891-5849 [Print] United States
PMID17462540 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antioxidants
  • Biomarkers
  • Coenzymes
  • PrPSc Proteins
  • Prions
  • Ubiquinone
  • coenzyme Q10
  • ubiquinone 9
Topics
  • Animals
  • Antioxidants (analysis, metabolism)
  • Biomarkers (analysis)
  • Brain (enzymology)
  • Cattle
  • Coenzymes (analysis, metabolism)
  • Disease Models, Animal
  • Encephalopathy, Bovine Spongiform (enzymology)
  • Lipid Metabolism
  • Mice
  • Mice, Transgenic
  • Oxidation-Reduction
  • Oxidative Stress
  • PrPSc Proteins (analysis, metabolism)
  • Prions (genetics)
  • Ubiquinone (analogs & derivatives, analysis, metabolism)
  • Up-Regulation

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