Human retinoic acid receptor-related orphan receptor alpha1 overexpression protects neurones against oxidative stress-induced apoptosis. - Archive ouverte HAL
Article Dans Une Revue Journal of Neurochemistry Année : 2006

Human retinoic acid receptor-related orphan receptor alpha1 overexpression protects neurones against oxidative stress-induced apoptosis.

Résumé

Retinoic acid receptor-related orphan receptor alpha (RORalpha) is a transcription factor belonging to the superfamily of nuclear receptors. Disruption of the Rora gene in the mouse results in a defect in the development of Purkinje cells leading to a cerebellar atrophy, which suggests a neuroprotective role for RORalpha. To test this hypothesis, the survival rate of lentiviral-mediated human RORalpha1-overexpressing neurones has been evaluated in response to different stressors disturbing the redox homeostasis, such as beta-amyloid peptide, c(2)-ceramide and H(2)O(2). We show that overexpression of human RORalpha1 provides neuroprotection by increasing the expression of the antioxidant proteins glutathione peroxidase 1 and peroxiredoxin 6, leading to a reduction in the accumulation of stress-induced reactive oxygen species. We further demonstrate that the neuroprotective effect of RORalpha is predominantly mediated by glutathione peroxidase 1 and peroxiredoxin 6. These results suggest a new role for RORalpha in the control of the neuronal oxidative stress and thus represents a new transcription factor of interest in the regulation of reactive oxygen species-induced neurodegenerative processes during ageing.

Dates et versions

hal-00083051 , version 1 (29-06-2006)

Identifiants

Citer

F. Boukhtouche, G. Vodjdani, C.I. Jarvis, J. Bakouche, B. Staels, et al.. Human retinoic acid receptor-related orphan receptor alpha1 overexpression protects neurones against oxidative stress-induced apoptosis.. Journal of Neurochemistry, 2006, 96, pp.1778-1789. ⟨10.1111/j.1471-4159.2006.03708.x⟩. ⟨hal-00083051⟩
38 Consultations
0 Téléchargements

Altmetric

Partager

More