Akt Inhibition as Preconditioning Treatment to Protect Kidney Cells against Anoxia
| العنوان: | Akt Inhibition as Preconditioning Treatment to Protect Kidney Cells against Anoxia |
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| المؤلفون: | Nicolas Melis, Romain Carcy, Isabelle Rubera, Marc Cougnon, Christophe Duranton, Michel Tauc, Didier F. Pisani |
| المساهمون: | Laboratoire de PhysioMédecine Moléculaire (LP2M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA) |
| المصدر: | International Journal of Molecular Sciences International Journal of Molecular Sciences, MDPI, 2022, 23 (1), pp.152. ⟨10.3390/ijms23010152⟩ International Journal of Molecular Sciences; Volume 23; Issue 1; Pages: 152 International Journal of Molecular Sciences, Vol 23, Iss 152, p 152 (2022) |
| بيانات النشر: | MDPI, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | triciribine, QH301-705.5, [SDV]Life Sciences [q-bio], ischemia, Kidney, Protective Agents, Catalysis, Article, Antioxidants, ROS, mitochondria, GC7, eIF5A, Inorganic Chemistry, 03 medical and health sciences, Mice, 0302 clinical medicine, Animals, Biology (General), Physical and Theoretical Chemistry, Phosphorylation, Hypoxia, Ischemic Preconditioning, QD1-999, Molecular Biology, Protein Kinase Inhibitors, Spectroscopy, Cells, Cultured, 030304 developmental biology, 0303 health sciences, Organic Chemistry, General Medicine, 3. Good health, Computer Science Applications, Mitochondria, Chemistry, Thiazoles, 030220 oncology & carcinogenesis, Reperfusion Injury, Methacrylates, Reactive Oxygen Species, Proto-Oncogene Proteins c-akt |
| الوصف: | International audience; 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1422-0067 1661-6596 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::67f4a85fa1afee38eeb662ddbafe2893Test http://europepmc.org/articles/PMC8745656Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....67f4a85fa1afee38eeb662ddbafe2893 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14220067 16616596 |
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