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Introduction. Les plaquettes contrôlent l'hémostase en adhérant à l'endothélium en cas de lésion et en s'agrégeant. Les mécanismes mis en œuvre dans ce processus physiologique sont similaires à ceux responsables de la thrombose artérielle, une complication grave de l'athérosclérose qui peut mener à un infarctus du myocarde potentiellement mortel. Des données obtenues au laboratoire ont montré qu'une phosphorylation élevée et soutenue de l'acétyl-CoA carboxylase (ACC) est observée dans les plaquettes de patients souffrant d'une maladie coronaire athéromateuse. L'isoforme ACC1, majoritaire dans les plaquettes, est une enzyme clé de la lipogenèse qui peut être régulée par des modifications post traductionnelles. Sa phosphorylation inhibe son activité. Hypothèse. Étant donné l'importance du rôle joué par de nombreux lipides dans les plaquettes tant au niveau de substrats énergétiques que de molécules de signalisation, nous postulons qu'une modulation de la phosphorylation/activité de l'ACC pourrait altérer les fonctions plaquettaires (adhésion, activation, agrégation, rétraction du clou plaquettaire et activité pro-coagulante) et/ou le métabolisme énergétique, et par conséquent affecter la formation ou la stabilité d'un thrombus. Méthodes. Dans ce travail, nous avons utilisé un inhibiteur pharmacologique de l'ACC, le TOFA. Des plaquettes humaines ont été pré-incubées en présence de TOFA 30µM pendant 2 heures puis stimulées avec de la thrombine. Nous avons mesuré la lipogenèse via l'incorporation de 14C-acide acétique dans les lipides. Les fonctions plaquettaires ont été mesurées par agrégométrie, cytométrie de flux et microscopie. L'expression et la phosphorylation de certains médiateurs de signalisation ont été examinées par western blot. Le métabolisme des plaquettes a été évalué via la mesure de la consommation d'oxygène. Résultats. Nos résultats montrent que le TOFA diminue la lipogenèse dans les plaquettes. Cette diminution est associée à une altération de la morphologie, à une inhibition de la sécrétion des granules denses et de l'agrégation plaquettaire induites par la thrombine tandis que l'activation du récepteur a.IIbJ33 et la sécrétion des granules a ne sont pas affectés, suggérant que le défaut d'agrégation provient d'une diminution des effets autocrines et paracrines de l'ADP et de l'ATP. Nous montrons que les mécanismes impliqués dans la diminution de la sécrétion des granules denses font intervenir les PKC, notamment la PKCδ, et leurs substrats, la cytohésine-2 et la PKD. De plus, nos résultats suggèrent qu'une diminution du contenu en phosphatidylsérine pourrait contribuer, en partie, à l'inhibition des PKC. À côté de son impact majeur sur la signalisation des plaquettes, le TOFA affecte aussi leur métabolisme énergétique en diminuant la capacité de réserve respiratoire et la respiration mitochondriale liée à la production d'ATP. Conclusion. Notre étude démontre qu’une inhibition soutenue de l’ACC diminue la lipogenèse et affecte la sécrétion des granules denses et l’agrégation via un ou plusieurs mécanismes dépendant des PKC et du métabolisme énergétique. Nous pensons que cela pourrait affecter la stabilité du thrombus chez les patients athéromateux. Introduction: Platelets adhere to the endothelium of vessels when there is a breach and lead to the formation of a clot. By this phenomenon, platelets control hemostasis. Mechanisms involved in this physiological process are similar to those responsible for arterial thrombosis that is a severe complication of atherosclerosis. This disease can lead to myocardial infarction and death. Acetyl-CoA carboxylase (ACC) regulates fatty acids synthesis and oxidation. Previous results from the lab showed that ACC is phosphorylated in platelets from patients with coronary artery disease, potentially due to persistent thrombin generation. ACC phosphorylation results in its inhibition. Aims: Given the primary roles of lipids in platelets structure, energy storage and signaling, we hypothesized that a sustained inhibition of ACC could have consequences on platelets activation and bioenergetics. Methods: To test our hypothesis, platelets were treated with 30µM TOFA, an ACC inhibitor, for 2 hours before thrombin stimulation. We measured lipogenesis via l4C-acetate incorporation into fatty acids. Platelet functions were assessed by aggregometry and flow cytometric studies. Signaling mediators were evaluated by western blot and platelet mitochondrial function was reflected by the oxygen consumption rate. Results: We show that a pre incubation of platelets with TOFA significantly decreased lipogenesis (Control: 6 pmol/min/10 9 platelets ± 0.8; TOFA: 1 pmol/min/10 9 platelets ± 0.3; P<0.05). This effect was accompanied by a significant defect in dense granules secretion and aggregation in response to Iow thrombin concentrations, whereas u-granules secretion was not affected, suggesting that the default in aggregation likely resulted from a lower autocrine and paracrine role of ADP. PKC activity is essential for granule secretion. Accordingly, we show that TOFA significantly decreased PKC substrates phosphorylation in baseline and after thrombin stimulation. Since PKCδ has been shown to play a role in dense granules regulation, the effects of TOFA on its activity was evaluated through the analysis of VASP phosphorylation. Indeed, inhibition of PKCδ has been shown to promote hyper phosphorylation of its Serl57 in platelets. Treatment with TOFA led to a drastic increase of Serl57 phosphorylation, in baseline and after thrombin stimulation, and in a cAMP-independent way. In addition, TOFA treatment significantly decreased phosphorylation of cytohesin-2 and PKD, two PKC substrates playing a critical role in dense granules secretion. Platelet metabolism was also affected by a sustained ACC inhibition, as shown by the TOFA-induced decrease in reserve capacity and ATP-linked respiration. Conclusion: Our study shows that a sustained inhibition of platelet ACC decreases lipogenesis and affects (i) dense granule secretion and aggregation through a PKC/ PKCδ - dependent mechanism, and (ii) platelet bioenergetics. We believe that it could affect thrombus stabilization in atherosclerotic patients.
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Biotin --- Metabolism --- Nutrition --- Poultry --- Pyruvate carboxylase --- Requirements
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La synthèse de glycogène et la lipogenèse sont stimulées par le gonflement cellulaire induit pas la glutamine. Ceci suggère que le gonflement pourrait jouer un rôle anabolique général et s’appliquer à d’autres voies anaboliques telle que la synthèse de cholestérol. Cette hypothèque est renforcée par le fait que l’enzyme-clé de cette voie métabolique, l’HMG-CoA réductase, est comme l’ACC activée par une protéine phosphatase de type-2A et inactivée par l’AMP-PK. Dès lors, par analogie avec l’ACC, l’HMG-CoA réductase pourrait être un substrat pour la GAPP et donc être activée par incubation des hépatocytes en présence de glutamine. Cette hypothèse a été testée au cours de ce mémoire
Hepatocytes --- Acetyl-CoA --- Carboxylase --- Hydroxymethylglutaryl-CoA Reductase Inhibitors
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Mitochondria --- Chloroplasts --- Genetics --- Congresses --- Congresses. --- Mitochondria - Congresses --- Chloroplasts - Congresses --- Genetics - Congresses --- Chloroplasts - congresses --- Mitochondria - congresses --- FERREDOXIN --- VARIEGATION --- GENETICS --- ORGANELLES --- MEMBRANES --- CHLOROPLASTS --- CILIATES --- YEASTS --- FUNGI --- HELA CELLS --- BIOGENESIS --- CHLOROPLAST GENETICS --- MITOCHONDRIA --- EPISOMES --- CYTOPLASMIC MALE STERILITY --- RIBULOSEDIPHOSPHATE CARBOXYLASE --- TOBACCO --- EVOLUTION --- HEREDITY --- SYNTHESIS
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Biotin --- Synthesis. --- Biotin. --- Biodermatin --- Biokur --- Biotin Gelfert --- Biotin Hermes --- Biotin-Ratiopharm --- Biotine Roche --- Deacura --- Gabunat --- Medebiotin --- Medobiotin --- Rombellin --- Vitamin H --- Biotin Ratiopharm --- Gelfert, Biotin --- Hermes, Biotin --- Roche, Biotine --- Avidin --- Multiple Carboxylase Deficiency --- Biotinidase Deficiency --- Holocarboxylase Synthetase Deficiency --- Coenzyme R --- Coenzymes --- Imidazoles --- Vitamin B complex
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Due to their lightweight and high specific strength, Mg-based alloys are considered as substitutes to their heavier counterparts in applications in which corrosion is non-relevant and weight saving is of importance. Furthermore, due to the biocompatibility of Mg, some alloys with controlled corrosion rates are used as degradable implant materials in the medical sector. The typical processing route of Mg parts incorporates a casting step and, subsequently, a thermo–mechanical treatment. In order to achieve the desired macroscopic properties and thus fulfill the service requirements, thorough knowledge of the relationship between the microstructure, the processing steps, and the resulting property profile is necessary. This Special Issue covers in situ and ex situ experimental and computational investigations of the behavior under thermo–mechanical load of Mg-based alloys utilizing modern characterization and simulation techniques. The papers cover investigations on the effect of rare earth additions on the mechanical properties of different Mg alloys, including the effect of long-period stacking-ordered (LPSO) structures, and the experimental and computational investigation of the effect of different processing routes
Arabidopsis --- abiotic stress response --- photosynthesis --- phosphoglycolate phosphatase --- photorespiration --- 2-phosphoglycolate --- Arabidopsis thaliana --- glycolate oxidase --- protein phosphorylation --- Zea mays --- Portulaca grandiflora --- C4 photosynthesis --- Crassulacean acid metabolism (CAM), evolution --- development --- PEP carboxylase --- Portulacaceae --- glycine decarboxylase --- metabolite signaling/acclimation --- TCA cycle --- Calvin–Benson cycle --- photoperiodic changes --- redox-regulation --- environmental adaptation --- Glycolate oxidase --- evolution --- Archaeplastida --- Cyanobacteria --- MCF --- oxidative phosphorylation --- mitochondrial carriers --- transporters --- energy balancing --- cyclic electron flux --- malate valve --- C3 cycle --- acclimation --- chlorophyll a fluorescence --- fluctuating light --- natural variation --- pyruvate kinase --- glycolysis --- respiratory metabolism --- n/a --- Calvin-Benson cycle
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Due to their lightweight and high specific strength, Mg-based alloys are considered as substitutes to their heavier counterparts in applications in which corrosion is non-relevant and weight saving is of importance. Furthermore, due to the biocompatibility of Mg, some alloys with controlled corrosion rates are used as degradable implant materials in the medical sector. The typical processing route of Mg parts incorporates a casting step and, subsequently, a thermo–mechanical treatment. In order to achieve the desired macroscopic properties and thus fulfill the service requirements, thorough knowledge of the relationship between the microstructure, the processing steps, and the resulting property profile is necessary. This Special Issue covers in situ and ex situ experimental and computational investigations of the behavior under thermo–mechanical load of Mg-based alloys utilizing modern characterization and simulation techniques. The papers cover investigations on the effect of rare earth additions on the mechanical properties of different Mg alloys, including the effect of long-period stacking-ordered (LPSO) structures, and the experimental and computational investigation of the effect of different processing routes
Research & information: general --- Technology: general issues --- Arabidopsis --- abiotic stress response --- photosynthesis --- phosphoglycolate phosphatase --- photorespiration --- 2-phosphoglycolate --- Arabidopsis thaliana --- glycolate oxidase --- protein phosphorylation --- Zea mays --- Portulaca grandiflora --- C4 photosynthesis --- Crassulacean acid metabolism (CAM), evolution --- development --- PEP carboxylase --- Portulacaceae --- glycine decarboxylase --- metabolite signaling/acclimation --- TCA cycle --- Calvin-Benson cycle --- photoperiodic changes --- redox-regulation --- environmental adaptation --- Glycolate oxidase --- evolution --- Archaeplastida --- Cyanobacteria --- MCF --- oxidative phosphorylation --- mitochondrial carriers --- transporters --- energy balancing --- cyclic electron flux --- malate valve --- C3 cycle --- acclimation --- chlorophyll a fluorescence --- fluctuating light --- natural variation --- pyruvate kinase --- glycolysis --- respiratory metabolism
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This book discusses biochemical adaptation to environments from freezing polar oceans to boiling hot springs, and under hydrostatic pressures up to 1,000 times that at sea level.Originally published in 1984.The Princeton Legacy Library uses the latest print-on-demand technology to again make available previously out-of-print books from the distinguished backlist of Princeton University Press. These editions preserve the original texts of these important books while presenting them in durable paperback and hardcover editions. The goal of the Princeton Legacy Library is to vastly increase access to the rich scholarly heritage found in the thousands of books published by Princeton University Press since its founding in 1905.
Adaptation (Physiology) --- Biochemistry. --- Biological chemistry --- Chemical composition of organisms --- Organisms --- Physiological chemistry --- Compensation (Physiology) --- Plasticity (Physiology) --- Composition --- Biology --- Chemistry --- Medical sciences --- Ecophysiology --- Biochemistry --- 57.017.32 --- 575.826 --- 575.826 Adaptation --- Adaptation --- Biologische wetenschappen in het algemeen. Biologie--?.017.32 --- 6-bisphosphatase. --- ATPase. --- Acid–base homeostasis. --- Adenosine monophosphate. --- Alanine. --- Alcohol dehydrogenase. --- Amino acid. --- Aminooxyacetic acid. --- Anabolism. --- Anaerobic glycolysis. --- Antifreeze. --- Arginine. --- Basal rate. --- Beta oxidation. --- Bohr effect. --- Carbohydrate. --- Carnitine. --- Catabolism. --- Catalase. --- Catalysis. --- Cellular respiration. --- Cofactor (biochemistry). --- Competitive inhibition. --- Cooperativity. --- Deep sea. --- Dehydrogenase. --- Detergent. --- Dissociation constant. --- Enzyme Repression. --- Enzyme inhibitor. --- Enzyme. --- Facultative anaerobic organism. --- Fatty acid. --- Fermentation. --- Flavin adenine dinucleotide. --- Fructose 1. --- Futile cycle. --- Glucagon. --- Gluconeogenesis. --- Glucose-6-phosphate dehydrogenase. --- Glucose. --- Glyceraldehyde 3-phosphate dehydrogenase. --- Glycerol. --- Glycogen phosphorylase. --- Glycogen. --- Glycogenolysis. --- Glycolysis. --- Hemoglobin. --- Hibernation. --- High-energy phosphate. --- Hill equation (biochemistry). --- Histidine. --- Hofmeister series. --- Hormone-sensitive lipase. --- Insulin. --- Isozyme. --- Ketosis. --- Lactic acid. --- Lipid. --- Lipolysis. --- Lysine. --- Mammalian diving reflex. --- Metabolic intermediate. --- Metabolism. --- Michaelis–Menten kinetics. --- Mitochondrial matrix. --- Mitochondrion. --- Molecular mimicry. --- Muscle. --- Nicotinamide adenine dinucleotide. --- Obligate anaerobe. --- Obligate. --- Organism. --- Ornithine. --- Osmolyte. --- Oxidative deamination. --- Peroxidase. --- Phosphagen. --- Phosphofructokinase. --- Phospholipid. --- Phosphorylase kinase. --- Proline. --- Proofreading (biology). --- Protein turnover. --- Protein. --- Proteolysis. --- Pyruvate carboxylase. --- Pyruvic acid. --- Redox. --- Regulatory enzyme. --- Root effect. --- Substrate-level phosphorylation. --- Thermoregulation. --- Thermus aquaticus. --- Thermus thermophilus. --- Triglyceride. --- Tryptophan. --- Turnover number. --- Urea cycle. --- Urea.
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