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

• Published in: Free radical biology & medicine 2007-06, Vol.42 (11), p.1723-1729
• Main Authors: Martin, Sergio F., Burón, Isabel, Espinosa, Juan C., Castilla, Joaquín, Villalba, José M., Torres, Juan M.
• Format: Article
• Language: English
• Subjects: Animals; Antioxidant; Antioxidants - analysis; Antioxidants - metabolism; Biomarkers - analysis; Brain - enzymology; BSE; Cattle; Coenzymes - analysis; Coenzymes - metabolism; CoQ; Disease Models, Animal; Encephalopathy, Bovine Spongiform - enzymology; Free radicals; Lipid Metabolism; Mice; Mice, Transgenic; Oxidation-Reduction; Oxidative Stress; Prion disease; Prions - genetics; PrP; PrPSc Proteins - analysis; PrPSc Proteins - metabolism; Ubiquinone - analogs & derivatives; Ubiquinone - analysis; Ubiquinone - metabolism; Up-Regulation
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2007.03.005

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.