Finely-tuned regulation of AMP-activated protein kinase is crucial for human adult erythropoiesis

International audienceAMP-activated protein kinase (AMPK) is a heterotrimeric complex containing α, β, and γ subunits involved in maintaining integrity and survival of murine red blood cells. Indeed, Ampk α1-/- , Ampk β1-/- and Ampk γ1-/- mice develop hemolytic anemia and the plasma membrane of their red blood cells shows elasticity defects. The membrane composition evolves continuously along erythropoiesis and during red blood cell maturation; defects due to the absence of Ampk could be initiated during erythropoiesis. We, therefore, studied the role of AMPK during human erythropoiesis. Our data show that AMPK activation had two distinct phases in primary erythroblasts. The phosphorylation of AMPK (Thr172) and its target acetyl CoA carboxylase (Ser79) was elevated in immature erythroblasts (glycophorin Alow), then decreased conjointly with erythroid differentiation. In erythroblasts, knockdown of the α1 catalytic subunit by short hairpin RNA led to a decrease in cell proliferation and alterations in the expression of membrane proteins (band 3 and glycophorin A) associated with an increase in phosphorylation of adducin (Ser726). AMPK activation in mature erythroblasts (glycophorin Ahigh), achieved through the use of direct activators (GSK621 and compound 991), induced cell cycle arrest in the S phase, the induction of autophagy and caspase-dependent apoptosis, whereas no such effects were observed in similarly treated immature erythroblasts. Thus, our work suggests that AMPK activation during the final stages of erythropoiesis is deleterious. As the use of direct AMPK activators is being considered as a treatment in several pathologies (diabetes, acute myeloid leukemia), this observation is pivotal. Our data highlighted the importance of the finely-tuned regulation of AMPK during human erythropoiesis

Laser bi-fréquences accordables pour la génération d'onde millimétrique et submillimétrique à haute cohérence.

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Dual frequency tunable laser system for a microwave and terahertz oscillator

International audienc

Oscillateur Micro-Onde à THz Ultra-Stable: Résultats Préliminaires

National audienceRésultats Préliminaires : Oscillateur Micro-Onde à THz Ultra-Stabl

Oscillateur micro-onde à térahertz ultra-stable

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Oscillateur micro-onde à térahertz ultra-stable

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Microwave to terahertz ultra-stable oscillator

Institute of Electrical and Electronics Engineers-Ultrasonics, Ferroelectrics and Frequency Control SocietyInternational audienc

High spectral purity microwave and terahertz oscillator

International audienceWe report on the design of an ultra stable microwave/THz oscillator and on the realization and the characterization of its laser source. The tunable oscillator is expected to show below -150 dB rad2/Hz phase instability at an offset frequency of 10 kHz for a 30 GHz carrier frequency, as well as 18 GHz, 100 GHz, 400 GHz and 1 THz carrier frequencies

Synthèse optique d'ondes hyperfréquences et millimétriques à très bas bruit de phase : résultats préliminaires

National audienceNous avons conçu et construit un système optique de synthèse d’ondes hyperfréquences, millimétriques et submillimétriques à très bas bruit de phase. Les résultats préliminaires montrent une densité spectrale de bruit de phase à 10 kHz de la porteuse d’une onde à 9 GHz limitée par l’appareil de mesure. Pour les bruits plus près de la porteuse, le bruit de phase est limité par une modulation d’amplitude résiduelle : le système est en cours de modifications