Cassagnes L. E., Chhour M., Perio Pierre, Sudor J., Gayon R., Ferry G., Boutin J. A., Nepveu F., Reybier K. (2018). Oxidative stress and neurodegeneration : the possible contribution of quinone reductase 2. Free Radical Biology and Medicine, 120, p. 56-61. ISSN 0891-5849.
Titre du document
Oxidative stress and neurodegeneration : the possible contribution of quinone reductase 2
Année de publication
2018
Auteurs
Cassagnes L. E., Chhour M., Perio Pierre, Sudor J., Gayon R., Ferry G., Boutin J. A., Nepveu F., Reybier K.
Source
Free Radical Biology and Medicine, 2018,
120, p. 56-61 ISSN 0891-5849
There is increasing evidence that oxidative stress is involved in the etiology and pathogenesis of neurodegenerative disorders. Overproduction of reactive oxygen species (ROS) is due in part to the reactivity of catecholamines, such as dopamine, adrenaline, and noradrenaline. These molecules are rapidly converted, chemically or enzymatically, into catechol-quinone and then into highly deleterious semiquinone radicals after 1-electron reduction in cells. Notably, the overexpression of dihydronicotinamide riboside: quinone oxidoreductase (QR2) in Chinese hamster ovary (CHO) cells increases the production of ROS, mainly superoxide radicals, when it is exposed to exogenous catechol-quinones (e.g. dopachrome, aminochrome, and adrenochrome). Here we used electron paramagnetic resonance analysis to demonstrate that the phenomenon observed in CHO cells is also seen in human leukemic cells (K562 cells) that naturally express QR2. Moreover, by manipulating the level of QR2 in neuronal cells, including immortalized neuroblast cells and ex vivo neurons isolated from QR2 knockout animals, we showed that there is a direct relationship between QR2-mediated quinone reduction and ROS overproduction. Supporting this result, the withdraw of the QR2 co-factor (BNAH) or the addition of the specific QR2 inhibitor S29434 suppressed oxidative stress. Taken together, these data suggest that the overexpression of QR2 in brain cells in the presence of catechol quinones might lead to ROS-induced cell death via the rapid conversion of superoxide radicals into hydrogen peroxide and then into highly reactive hydroxyl radicals. Thus, QR2 may be implicated in the early stages of neurodegenerative disorders.
Plan de classement
Sciences fondamentales / Techniques d'analyse et de recherche [020]
;
Santé : généralités [050]
Localisation
Fonds IRD [F B010072833]
Identifiant IRD
fdi:010072833
