33 research outputs found

    Coup de chaud sur les polymères

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    Rheology of preceramic polymers

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    Boron Nitride Nanoparticles: One-step synthesis from single-source preceramic precursors

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    Metabolomics Profile of the Secretome of Space-Flown Oligodendrocytes

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    Intracranial hypertension (ICP) and visual impairment intracranial pressure (VIIP) are some of the sequels of long-term space missions. Here we sought to determine how space microgravity (µG) impacts the metabolomics profile of oligodendrocyte progenitors (OLPs), the myelin-forming cells in the central nervous system. We report increased glutamate and energy metabolism while the OLPs were in space for 26 days. We also show that after space flight, OLPs (SPC OLPs) display significantly increased mitochondrial respiration and glycolysis. These data are in agreement with our previous work using simulated microgravity. In addition, our global metabolomics approach allowed for the discovery of endogenous metabolites secreted by OLPs while in space that are significantly modulated by microgravity. Our results provide, for the first time, relevant information about the energetic state of OLPs while in space and after space flight. The functional and molecular relevance of these specific pathways are promising targets for therapeutic intervention for humans in long-term space missions to the moon, Mars and beyond

    Regulation of membrane cholecystokinin-2 receptor by agonists enables classification of partial agonists as biased agonists.

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    International audienceGiven the importance of G-protein-coupled receptors as pharmacological targets in medicine, efforts directed at understanding the molecular mechanism by which pharmacological compounds regulate their presence at the cell surface is of paramount importance. In this context, using confocal microscopy and bioluminescence resonance energy transfer, we have investigated internalization and intracellular trafficking of the cholecystokinin-2 receptor (CCK2R) in response to both natural and synthetic ligands with different pharmacological features. We found that CCK and gastrin, which are full agonists on CCK2R-induced inositol phosphate production, rapidly and abundantly stimulate internalization. Internalized CCK2R did not rapidly recycle to plasma membrane but instead was directed to late endosomes/lysosomes. CCK2R endocytosis involves clathrin-coated pits and dynamin and high affinity and prolonged binding of β-arrestin1 or -2. Partial agonists and antagonists on CCK2R-induced inositol phosphate formation and ERK1/2 phosphorylation did not stimulate CCK2R internalization or β-arrestin recruitment to the CCK2R but blocked full agonist-induced internalization and β-arrestin recruitment. The extreme C-terminal region of the CCK2R (and more precisely phosphorylatable residues Ser(437)-Xaa(438)-Thr(439)-Thr(440)-Xaa(441)-Ser(442)-Thr(443)) were critical for β-arrestin recruitment. However, this region and β-arrestins were dispensable for CCK2R internalization. In conclusion, this study allowed us to classify the human CCK2R as a member of class B G-protein-coupled receptors with regard to its endocytosis features and identified biased agonists of the CCK2R. These new important insights will allow us to investigate the role of internalized CCK2R*β-arrestin complexes in cancers expressing this receptor and to develop new diagnosis and therapeutic strategies targeting this receptor
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