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Article dans une revue

Identification of GCN2 as new redox regulator for oxidative stress prevention in vivo

Abstract : Constitution of oxidative defense systems and, correspondingly, oxidative stress prevention are highly dependent on amino acid supply. In vitro, experiments have demonstrated that amino acid availability participates to the homeostasis of reactive oxygen species. However the molecular mechanisms involved in the maintenance of redox homeostasis responsive to circulating amino acid levels remain unclear. As GCN2 is a protein kinase considered to be an important sensor for amino acids availability and a potential regulator of redox homeostasis, we hypothesized that this kinase can modulate redox homeostasis in vivo, in response to an amino acid-imbalanced diet. We investigated the response of GCN2 and GCN2-/- mice to a long-term (24 weeks) leucine-imbalanced diet (ED Delta Leu). In order to evaluate the oxidation level in each group of mice, we determined the degree of protein oxidation in the liver. Interestingly, GCN2-/- mice exhibited an increase in protein carbonylation, a marker of oxidative stress, in response to the ED Delta Leu diet. These data correlate with a decrease in hepatic GPX1 expression, a major antioxidant enzyme, and a decrease in total GPX activity in the liver. Our results suggest that GCN2 and its downstream signaling pathway have an important role in the protection against oxidative injuries induced by an amino acid-imbalanced diet, and that it can play a critical role in the prevention of oxidative damage.
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https://hal.inrae.fr/hal-02645943
Déposant : Migration Prodinra <>
Soumis le : vendredi 29 mai 2020 - 03:29:32
Dernière modification le : vendredi 12 juin 2020 - 10:43:26

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Cedric Chaveroux, Sarah Lambert-Langlais, Laurent Parry, Valerie Carraro, Celine Jousse, et al.. Identification of GCN2 as new redox regulator for oxidative stress prevention in vivo. Biochemical and Biophysical Research Communications, Elsevier, 2011, 415 (1), pp.120 - 124. ⟨10.1016/j.bbrc.2011.10.027⟩. ⟨hal-02645943⟩

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