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Article Dans Une Revue Cell Death and Disease Année : 2021

Inhibition of eIF5A hypusination reprogrammes metabolism and glucose handling in mouse kidney

Michel M. Tauc
Didier Pisani

Résumé

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.
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Dates et versions

hal-03176556 , version 1 (28-09-2021)

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Marc Cougnon, Romain Carcy, Nicolas Melis, Isabelle Rubera, Christophe Duranton, et al.. Inhibition of eIF5A hypusination reprogrammes metabolism and glucose handling in mouse kidney. Cell Death and Disease, 2021, 12 (4), ⟨10.1038/s41419-021-03577-z⟩. ⟨hal-03176556⟩
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