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Article dans une revue International Journal of Molecular Sciences Année : 2022

Akt Inhibition as Preconditioning Treatment to Protect Kidney Cells against Anoxia

Nicolas Melis
Romain Carcy
  • Fonction : Auteur
Marc Cougnon
  • Fonction : Auteur
Christophe Duranton
Michel Tauc

Résumé

Lesions issued from the ischemia/reperfusion (I/R) stress are a major challenge in human pathophysiology. Of human organs, the kidney is highly sensitive to I/R because of its high oxygen demand and poor regenerative capacity. Previous studies have shown that targeting the hypusination pathway of eIF5A through GC7 greatly improves ischemic tolerance and can be applied successfully to kidney transplants. The protection process correlates with a metabolic shift from oxidative phosphorylation to glycolysis. Because the protein kinase B Akt is involved in ischemic protective mechanisms and glucose metabolism, we looked for a link between the effects of GC7 and Akt in proximal kidney cells exposed to anoxia or the mitotoxic myxothiazol. We found that GC7 treatment resulted in impaired Akt phosphorylation at the Ser473 and Thr308 sites, so the effects of direct Akt inhibition as a preconditioning protocol on ischemic tolerance were investigated. We evidenced that Akt inhibitors provide huge protection for kidney cells against ischemia and myxothiazol. The pro-survival effect of Akt inhibitors, which is reversible, implied a decrease in mitochondrial ROS production but was not related to metabolic changes or an antioxidant defense increase. Therefore, the inhibition of Akt can be considered as a preconditioning treatment against ischemia.
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Dates et versions

hal-03507337, version 1 (03-01-2022)

Licence

Paternité - CC BY 4.0

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Nicolas Melis, Romain Carcy, Isabelle Rubera, Marc Cougnon, Christophe Duranton, et al.. Akt Inhibition as Preconditioning Treatment to Protect Kidney Cells against Anoxia. International Journal of Molecular Sciences, 2022, 23 (1), pp.152. ⟨10.3390/ijms23010152⟩. ⟨hal-03507337⟩
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