Inhibition of eIF5A hypusination reprogrammes metabolism and glucose handling in mouse kidney
| العنوان: | Inhibition of eIF5A hypusination reprogrammes metabolism and glucose handling in mouse kidney |
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| المؤلفون: | Marc Cougnon, Karine Dumas, Christophe Duranton, Nicolas Soubeiran, Catherine Pons, Isabelle Rubera, Didier F. Pisani, Luc Pellerin, Sébastien Giraud, Thierry Hauet, Romain Carcy, Marina Shkreli, Jean-François Tanti, Nicolas Blondeau, Nicolas Melis, Michel Tauc |
| 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), Hôpital Pasteur [Nice] (CHU), National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Centre méditerranéen de médecine moléculaire (C3M), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), ANR-19-CE18-0029,KIRI,Ciblage de l'agression ischémique, application à la transplantation d'organes(2019), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Pisani, Didier, Ciblage de l'agression ischémique, application à la transplantation d'organes - - KIRI2019 - ANR-19-CE18-0029 - AAPG2019 - VALID |
| المصدر: | Cell Death and Disease, Vol 12, Iss 4, Pp 1-14 (2021) Cell Death & Disease Cell Death and Disease Cell Death and Disease, Nature Publishing Group, 2021, 12 (4), ⟨10.1038/s41419-021-03577-z⟩ Cell Death and Disease, 2021, 12 (4), ⟨10.1038/s41419-021-03577-z⟩ |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, Cancer Research, Physiology, Immunology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Oxidative phosphorylation, Kidney, Article, Mice, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Peptide Initiation Factors, medicine, Animals, lcsh:QH573-671, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, 030304 developmental biology, 0303 health sciences, biology, lcsh:Cytology, Chemistry, Glucose transporter, RNA-Binding Proteins, Cell Biology, Metabolism, Cell biology, Renal glucose reabsorption, Glucose, medicine.anatomical_structure, Anaerobic glycolysis, Renal physiology, biology.protein, GLUT1, 030217 neurology & neurosurgery |
| الوصف: | Inhibition of the eukaryotic initiation factor 5A activation by the spermidine analogue GC7 has been shown to protect proximal cells and whole kidneys against an acute episode of ischaemia. The highlighted mechanism involves a metabolic switch from oxidative phosphorylation toward glycolysis allowing cells to be transiently independent of oxygen supply. Here we show that GC7 decreases protein expression of the renal GLUT1 glucose transporter leading to a decrease in transcellular glucose flux. At the same time, GC7 modifies the native energy source of the proximal cells from glutamine toward glucose use. Thus, GC7 acutely and reversibly reprogrammes function and metabolism of kidney cells to make glucose its single substrate, and thus allowing cells to be oxygen independent through anaerobic glycolysis. The physiological consequences are an increase in the renal excretion of glucose and lactate reflecting a decrease in glucose reabsorption and an increased glycolysis. Such a reversible reprogramming of glucose handling and oxygen dependence of kidney cells by GC7 represents a pharmacological opportunity in ischaemic as well as hyperglycaemia-associated pathologies from renal origin. |
| وصف الملف: | application/pdf |
| تدمد: | 2041-4889 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::655dd5b4627b72eeeb1aacf950dab4beTest https://doi.org/10.1038/s41419-021-03577-zTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....655dd5b4627b72eeeb1aacf950dab4be |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20414889 |
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