Дисертації з теми "Récepteurs de la thrombine"
Оформте джерело за APA, MLA, Chicago, Harvard та іншими стилями
Ознайомтеся з топ-50 дисертацій для дослідження на тему "Récepteurs de la thrombine".
Біля кожної праці в переліку літератури доступна кнопка «Додати до бібліографії». Скористайтеся нею – і ми автоматично оформимо бібліографічне посилання на обрану працю в потрібному вам стилі цитування: APA, MLA, «Гарвард», «Чикаго», «Ванкувер» тощо.
Також ви можете завантажити повний текст наукової публікації у форматі «.pdf» та прочитати онлайн анотацію до роботи, якщо відповідні параметри наявні в метаданих.
Переглядайте дисертації для різних дисциплін та оформлюйте правильно вашу бібліографію.
Faraut, Brice. "Synaptogénèse et plasticité neuromusculaire : conséquences de l'activation du récepteur de la thrombine, PAR-1." Paris 5, 2004. http://www.theses.fr/2004PA05P612.
Thrombin is a serine protease that regulates numerous cellular functions by activating via specific proteolytic cleavage a family of G-protein-coupled receptors (PARs). The thrombin receptor PAR-1 and the thrombin inhibitor protease nexin-1 are both expressed by muscle cells during the formation of the neuromuscular junction (NMJ). We have then hypothesized that thrombin was involved in the formation and plasticity of the NMJ. We show in myotubes in vitro that thrombin, by activating PAR-1, decreases the expression of the acetylcholine receptor (AChR) while its specific inhibitor, hirudin, increases its expression. In addition, this effect of thrombin is mediated through intracellular calcium signals IP3 receptor-dependent. Then, in neuron-myotube cocultures, we show that thrombin via PAR-1 decreases neuromuscular contact size whereas hirudin has the opposite effect. Therefore, we have studied the expression of the muscle-specific tyrosine-kinase receptor, MuSK, which activation leads to the aggregation of AChRs mediated by rapsyn and of other post-synaptic proteins during the formation of neuromuscular contacts. We find that rapsyn expression is not changed but the one of MuSK is reduced in presence of thrombin. In conclusion, this study reveals a signaling pathway for AChR regulation by thrombin and significant modifications of neuromuscular synaptogenesis when MuSK and AChR levels are reduced by thrombin. Recently, mutations in MuSK gene have been identified by our team for the first time in neuromuscular human pathology. To study the pathogen features of these mutations, this latter have been expressed in muscle cells and the repercussion on neuromuscular synaptogenesis were analysed in vitro. We find that a nonsense mutation of the intracellular domain of MuSK decreases AChR e-subunit gene transcription and also induces an exuberant axonal growth in neuron-myotube cocultures. All together, this data contribute to a better comprehension of the mechanisms involved in the formation and the maintenance of the NMJ
Zolotoff, Cindy. "Effets combinés de l'hypoxie intermittente et de la thrombine sur un modèle in vitro de Barrière Hémato-Encéphalique." Electronic Thesis or Diss., Lyon, 2021. http://www.theses.fr/2021LYSES020.
Obstructive sleep apnea (OSA) is characterized by decreases or cessation of airflow followed by periods of reoxygenation. Several studies suggest a link with the onset of neurodegenerative diseases that could be due to an alteration of the blood-brain barrier (BBB), an interface that protects the brain from potential harmful compounds. This interface is made up of endothelial cells connected by junctional proteins that limit passage, and they also possess efflux pumps that play a role in detoxifying molecules. Repeated episodes of intermittent hypoxia (IH) would be at the origin of the alteration of this BBB. Other factors could be involved since OSA also increases the incidence of vascular pathologies and thrombin, a coagulation protease acting through its PAR receptors, could be increased. We therefore developed a cellular model of IH which allowed us to see that IH induced: a disruption of the BBB marked by a decrease in the expression of junction proteins, an increase in permeability and a deregulation of efflux pumps. Next, we combined IH and thrombin at two concentrations. IH alone or combined with a high dose of thrombin increases BBB permeability and PAR-1 expression, an effect that can be reversed by the use of dabigatran. IH combined with a lower dose of thrombin limits BBB permeability and increases PAR-3 expression. Thus, this work has allowed a first approach of the cellular mechanisms taking place in OSA
Saci, Abdelhafid. "Etude de la signalisation plaquettaire : implication de p120Cbl, phosphatidylinositol 3-kinase (PI 3-K) et Grb2." Paris 5, 2001. http://www.theses.fr/2001PA05P605.
Blood platelets are anucleated and terminaly differenciated cells. A number of receptors are present on platelet membrane and mediate signalling and activation in response to various agonists. The action of an agonist triggers an inside-out signalling which activates αIIb-β3 integrin. The latter becomes able to link fibrinogen and transduces a secondary outside-in signalling. We first studied the involvement of the adoptor protein, Cbl, and of the lipid kinase, PI 3-K, in platelet signalling mediated by (i) the receptor for Fc domain of IgG (FcγRIIa), (ii) by the αIIb-β3 integrin (outside-in) and (iii) by the thrombin receptor. .
Jumeau, Céline. "La thrombine et son récepteur PAR-1 comme cibles thérapeutiques dans la prévention et le traitement de la dilatation atriale." Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066242.
Atrial fibrillation (AF) is the most common cardiac arrhythmia. It is characterized by a disorganized and ineffective contraction of the atria and structural changes of the myocardium. Endothelial dysfunction, maintained by inflammation, activate the coagulation cascade and thrombin generation, promoting intra-atrial thrombus formation. Prevention of thromboembolism is a major issue in the management of AF and is done by long-term prescription of oral anticoagulants among which a direct thrombin inhibitor, dabigatran. Our hypothesis is that excess thrombin maintains structural changes in the myocardium via the PAR-1 receptor (protease activated receptor-1) of circulating and myocardial cells. The objective is to identify the signaling pathway of thrombin involved in the atrial remodeling. In an atrial dilatation model associated with arrhythmogenic substrate and hypercoagulability, administration of direct thrombin inhibitors or antagonists of PAR-1 oral reduce expansion and arrhythmic susceptibility of the left atrium. These treatments inhibit the induction of myocyte hypertrophic response markers, β-MHC and BNP and remodeling of the extracellular matrix markers, CTGF and PAI-1. With explant of left atria culture, we show that these phenotypic changes are induced by the Rho pathway / ROCK and STAT3 transcription factor. Our results also indicate that the expression and activity of ErbBs receptors known to be transactivated via PAR-1, are modified during development of atrial dilatation. Thrombin participates in these changes only when the atrial remodeling is established. These results show that thrombin participates in atrial remodeling associated with an arrhythmogenic substrate, and direct thrombin inhibitors and PAR-1 antagonists are potential therapeutic agents to prevent the development of atrial dilation
Li, Ruo Ya. "Clonage d'une tyrosine-phosphatase membranaire (HPTP-béta) et étude de l'implication de la SH-PTP1 dans l'agrégation plaquettaire induite par la thrombine." Toulouse 3, 1995. http://www.theses.fr/1995TOU30150.
Gaits-Iacovoni, Frédérique. "Intervention de protéine tyrosine phosphatases dans l'inhibition de contact des cellules endothéliales et dans l'activation de cellules mégacaryoblastiques." Toulouse 3, 1995. http://www.theses.fr/1995TOU30245.
Guinebault, Christine. "Activation plaquettaire par l'alpha-thrombine : modes de régulation de la phosphatidylinositol 3-kinase et de la phospholipase C-gamma, en relation avec l'organisation du cytosquelette." Toulouse 3, 1994. http://www.theses.fr/1994TOU30261.
Mokrane, Ahmed. "Modélisation de la réactivité enzymatique par le formalisme LSCF et étude des effets électrostatiques à longue distance : application à l'activation du récepteur de la thrombine." Nancy 1, 1997. http://docnum.univ-lorraine.fr/public/SCD_T_1997_0272_MOKRANE.pdf.
Dufourcq, Pascale. "La thrombomoduline, un marqueur de la lésion endothéliale : approche clinique et expérimentale dans la maladie athéromateuse." Bordeaux 2, 1994. http://www.theses.fr/1994BOR2P019.
Smadja, David. "Rôle du récepteur de la thrombine PAR-1 dans l'expansion des progéniteurs endothéliaux." Paris 5, 2006. http://www.theses.fr/2006PA05P625.
The injection of endothelial progenitor cells (EPCs) in preclinical models of ischemia has been shown to enhance neovascularization. However, the scarcity of EPCs in human peripheral blood is a limitation for of its use as a cell therapy product, and the development of an expansion procedure is a crucial issue. In this work, we have characterized EPCs during in vitro expansion, using EPCs derived from cord blood CD34+ cells. An increased expression of KDR/VEGFR2 along expansion was observed, together with an increase of in vitro angiogenic properties. We also show the presence of the thrombin receptor PAR-1 on expanded EPCs. The importance of PAR-1 in blood vessel development has been demonstrated in knockout mice. As EPCs are thought to be involved in postnatal vasculogenesis, we examined the effect of PAR-1 activation on EPCs. PAR-1 activation induced EPCs proliferation, resulting of an angiopoietin 2 upregulation. PAR-1 activation also enhanced actin reorganization, promoting both spontaneous migration in a Boyden chamber assay and migration toward SDF-1. Finally, PAR-1 stimulation by SFLLRN increased the formation of capillary-like structures formed by EPCs in Matrigel, and this effect was abrogated by anti-CXCR-4 and anti-SDF-1 antibodies. All together, PAR-1 activation on cord blood derived EPCs led to a proangiogenic effect. In vivo, enhancement of angiogenic properties of EPCs by thrombin generated at the target site might promote vasculogenesis and thrombus resorption. Our data suggest that SFLLRN peptide could be used to expand cord blood derived-EPCs ex vivo. However, this effect was not found on EPCs isolated from adult blood, underlining the usefulness of a procedure designed to mobilize immature endothelial cells from bone marrow to peripheral blood
Chieng, Yane Pauline. "Signalisation endothéliale des récepteurs thrombomoduline, PAR-1 et ErbB : rôle dans le remodelage vasculaire et auriculaire." Paris 5, 2010. http://www.theses.fr/2010PA05P623.
The α-thrombin is a serine-protease involved in the maintenance of vascular function. Thrombin has ambivalent functions through its two receptors, PAR-1 and thrombomodulin. Thrombomodulin has anti-inflammatory and anti-proliferative properties but it signaling still remains to be characterized. I first demonstrated that thrombin binding to thrombomodulin induces the release of soluble thrombomodulin fragments to activate the tyrosine kinase receptors, EGFR and ErbB2 and inhibits monocyte adhesion to endothelium and PAR-1 pro-inflammatory signals. Using models of atrial remodeling and restenosis in rats, we showed that thrombomodulin transcription is down regulated while PAR-1 signaling is activated. A PAR-1 inhibitor prevents atrial dilation by stimulating the anti-apoptotic ErbB2 signaling pathway but has no effect on thrombomodulin transcription. It also inhibits angioplasty-induced restenosis without preventing early decrease in expression of thrombomodulin, EGFR and ErbB2. Thus, dysfunction of the balance between the signaling pathways of thrombomodulin and PAR-1 results in tissue remodeling and inflammatory processes. So, PAR-1 inhibitors have a therapeutic potential and thrombomodulin is a new therapeutic target for cardiovascular and proliferative diseases
Nguyen, Quang-Dé. "Signalisation du récepteur PAR-I de la thrombine dans l'invasion cellulaire et la carcinogenèse colique." Paris 6, 2004. http://www.theses.fr/2004PA066248.
Yin, Xing. "Mécanismes d'activation des cellules musculaires lisses par l'angiotensine II et la thrombine : influence des ions calcium et rôles du récepteur de l'EGF et des protéines SRC." Paris 6, 2004. http://www.theses.fr/2004PA066338.
Cazes, Eric. "Aspects biologiques et cliniques sur le rôle du récepteur de la thrombine, PAR-1, dans les plaquettes." Bordeaux 2, 1999. http://www.theses.fr/1999BOR28638.
Lagrange, Jérémy. "Changements hémostatiques du syndrome métabolique, de l'hypertension artérielle, et de l'insuffisance cardiaque : approches physiologique et physiopathologique." Thesis, Université de Lorraine, 2013. http://www.theses.fr/2013LORR0160/document.
Increasing life span has made heart failure (HF) a major issue for public health. The metabolic syndrome (MetS) and hypertension are two important factors which can lead to HF. Structural and cellular modification occurring in the arterial wall in the MetS, hypertension and HF may provoke hemostasis alterations that can worsen the clinical situation. We have shown in this work, hemostasis modifications in animal models of pathologies implicated in HF development. Hemostasis alterations were shown to precede functional modifications of the arterial wall and could favor HF development in Zucker rats. Spontaneously hypertensive rats showed an arterial wall hypercoagulability via smooth muscle cells. These results don't permit the implication of hypertension in the hypercoagulable state found in the Zucker rat. A mouse model with aldosterone receptor activation in the endothelium lead to a hypocoagulable state by increasing the protein C anticoagulant system via his receptor, the EPCR. Studying a human HF patient cohort permitted the measurement of cardiac function and of arterial stiffness parameters. This characterization is important to understand thrombosis events associated with HF in humans. The general conclusion of this work is that, in pathologies leading to HF, modification of hemostasis to a procoagulable state, implicates the arterial wall
Carteaux, Jean-Philippe. "Circulation extra-corporelle, thrombose artérielle : modèles expérimentaux : rôle de l'inhibition des récepteurs plaquettaires GP IIb-IIIa." Nancy 1, 1996. http://www.theses.fr/1996NAN10340.
Pinet, Caroline. "Effets de la thrombine sur les courants sodiques rapide et persistant, dans les myocytes atriaux humains, et les cellules CHO transfectées avec hNav1. 5." Paris 7, 2003. http://www.theses.fr/2003PA077097.
Baurand, Anthony. "Les récepteurs à l'ADP des plaquettes sanguines : 1.Régulation au cours de l'activation plaquettaire et désensibilisation. 2.Cibles de nouvelles molécules antithrombotiques." Université Louis Pasteur (Strasbourg) (1971-2008), 2002. http://www.theses.fr/2002STR13138.
Valéra, Marie-Cécile. "Étude de l'effet des oestrogènes sur la fonction plaquettaire : rôle des récepteurs [alpha] et [béta] des oestrogènes." Toulouse 3, 2009. http://www.theses.fr/2009TOU30327.
Although estrogens are recognized to favour a deleterious effect on the venous thrombosis risk and a preventive action on the development of arterial atheroma, their effect on platelet functions in vivo remains unclear. The main aim of this work was to evaluate the impact of a chronic treatment of oestradiol (E2) on platelet functions in mouse. Platelets from E2-treated mice showed a marked decrease in their responsiveness ex-vivo compared to non-treated mice. Accordingly, E2 treatment increased tail bleeding time and elicited an impressive resistance to thromboembolism following injection of an epinephrin-collagen mix. Haematopoietic transgenic chimera mice demonstrated that E2 action on bleeding time and thromboembolism resistance was mediated by the haematopoietic ER alpha but not ER béta and that ER alpha activation function-1 was dispensable. Altogether, we demonstrate that E2 can elicit an antiaggregant action in an ER alpha-dependent, activation function-1-independent manner, opening the way for new potential strategies for antithrombotic and vasculoprotective therapies
Kammerer, Nadège. "Rôle des récepteurs purinergiques plaquettaires dans la thrombose expérimentale localisée et étude du temps de saignement chez la souris." Université Louis Pasteur (Strasbourg) (1971-2008), 2004. http://www.theses.fr/2004STR13151.
Addi, Tawfik. "Identification des partenaires moléculaires répondant à l'activation d'Aryl hydrocarbon Receptor par les toxines urémiques." Thesis, Aix-Marseille, 2019. http://www.theses.fr/2019AIXM0127.
The main complication of chronic kidney disease is cardiovascular disease. Accumulation of uremic toxins derived from the tryptophan metabolism indole-3-acetic acid (IAA) and Indoxyl sulfate (IS) pathways, are involved in a key phenomenon of cardiovascular events; thrombosis. These toxins induce the expression and pro-coagulant activity of tissue factor (TF), the main cellular initiator of blood coagulation. The transcription factor, Aryl Hydrocarbon Receptor (AHR), a cellular receptor for indole toxins, is involved in the induction of endothelial TF. The mechanisms by which AhR controls the expression of TF in endothelial cells are poorly understood. The main objective of this thesis was to determine the signaling pathways and transcription factors involved in the expression of AhR mediated TF and induced by the IAA and the SI.The expression of IAA-mediated TF and endothelial IS is controlled primarily by transcription. The IAA and the IS are activating the classical genomic AhR pathway. However, the expression of TF is not mediated by this way. Activation of TF in response to the IAA passes through an AhR-p38MAPK-NF-kB pathway.In conclusion, induction by IAA of TF in human endothelial cells involves the non-genomic pathway of AhR-p38MAPK / NF-KB. The identification of this signaling pathway suggests that we can dissociate the detrimental effect of AhR depending on the genomic pathway, the prothrombotic effect
Croizet, François. "Modélisation et conception d'antagonistes du récepteur plaquettaire du fibrinogène (αIIb/ß3 - GP IIb/IIIa)". Bordeaux 2, 1997. http://www.theses.fr/1997BOR2B006.
Makhloufi, Camelia. "Rôle de l’Aryl Hydrocarbon Receptor dans la thrombose durant la maladie rénale chronique." Thesis, Aix-Marseille, 2019. http://www.theses.fr/2019AIXM0585.
Chronic kidney disease (CKD) is a public health problem whose main complication is cardiovascular disease (CVD). Thrombosis is a key factor in the progression of CVD. CKD is characterized by the accumulation of uremic toxins (UT). Our team demonstrated that indolic UTs, including indoxyl sulfate (IS), induced the expression and activity of tissue factor (TF), the main trigger for the coagulation cascade, via the activation of the transcription factor Aryl Hydrocarbon Receptor (AhR). To understand the mechanisms involved in the formation of a prothrombotic state during CKD, we compared two mouse models: 5/6th nephrectomy and adenine diet (AR). Both models have coagulation activation. RA has more severe renal failure and a hemorrhagic tendency absent in the nephrectomy model. The use of AR in mice invalidated for AhR has been a failure. This model is resistant to the induction of renal insuffisency. In conclusion, our work confirms the importance of thorough characterization of a model before its use. The adenine model summarizes all hemostasis disorders during the MRC but is not a good model for studying the role of AhR in them
Ducros, Elodie. "Cancer et thrombose : Le rôle du récepteur de la protéine C." Paris 11, 2009. http://www.theses.fr/2009PA11T061.
Bertolino, Frédéric. "Caractérisation et modulation pharmacologiques d'effets cardiovasculaires aigus liés à l'activation du récepteur au thromboxane A2/endopéroxyde." Bordeaux 2, 1995. http://www.theses.fr/1995BOR28355.
Marque, Pierre-Emmanuel. "Modulation de l'activité de la thrombine." Paris 5, 2002. http://www.theses.fr/2002PA05P625.
Blood coagulation results in sequential activation of plasma proenzyme to their enzyme form. This burst of activation is very selective and auto-regulated. It is the last enzyme (thrombin) who controls directely and indirectely this cascade. Thrombin activity is regulated through three mechanisms 1) an auto-control of its generation, 2) modulation by thrombomodulin and 3) neutralization by antithrombin. The last two mechanisms were discussed in this thesis, especially Protein C activation which is the only inductible anticoagulant system. Direct neutralization of thrombin by antithrombin was investigated through the characterization of a monoclonal antibody that selectively recognizes complexed antithrombin. This antibody reacts with none of the monomeric conformers of antithrombin. These observations limit drastically the possible locations of the defeated protease within the complex. .
Rafowicz, Stéphane. "L'hirudine : un inhibiteur spécifique de la thrombine." Paris 5, 1999. http://www.theses.fr/1999PA05P130.
GANDOSSI, ERIC. "Pharmacologie de la thrombine associee au caillot." Paris 7, 1999. http://www.theses.fr/1999PA077093.
Eliautou, Sandra. "Signalisation déclenchée par le complexe GPIb-V-IX et émission de filopodes dans la plaquette sanguine." Strasbourg, 2009. https://publication-theses.unistra.fr/public/theses_doctorat/2009/ELIAUTOU_Sandra_2009.pdf.
Marque, Pierre-Emmanuel. "Rôle des exosites dans la régulation allostérique de la thrombine." Paris 5, 1998. http://www.theses.fr/1998PA05P212.
Bouton, Marie-Christine. "Specificite de la thrombine humaine. Relations structure-fonctions." Paris 7, 1994. http://www.theses.fr/1994PA077210.
CHEN, LI XIN. "Relation structure-fonction du recepteur de la thrombine." Paris 11, 1998. http://www.theses.fr/1998PA112266.
Sanchez, Caroline. "Influences génétique et environnementale de la génération de thrombine." Thesis, Aix-Marseille 2, 2011. http://www.theses.fr/2011AIX20658.
In this work, we studied genetic and environmental modulators of thrombin generation by endogenous thrombin potential (ETP).We showed that plasma levels of antithrombin (AT) can be considered as risk factors for thrombosis. ETP levels are higher in patients presenting a quantitative defect of AT. In addition, mutation AT Cambridge II is also associated with an increase of ETP. Besides the AT, we confirmed a positive effect of the prothrombin 20210A allele on thrombin generation, especially in presence of venous thrombosis antecedents. These contributions, we have confirmed the role of plasma fibrinogen and factor II, blood group and oral contraceptives on thrombin generation.In addition, our results also showed an effect of high fat diet on thrombin generation in rats. Conversely to the standard fat diet, high fat diet maintened high levels of ETP after weaning. High fat diet-induced effects persisted four weeks after switching to standard fat diet. This effect could be partially explained by higher rates of coagulation factors VII and did not follow classical changes in glucidolipidic metabolism.In conclusion our data suggest that ETP can be considered as an indicator of the prothrombotic state in patients, but require more explanation to predict a risk of venous thrombosis. The measurement of thrombin generation may be a useful tool for assessing the impact of changes in diet or medication to treat obesity on circulating procoagulant potential
Khamlichi, Samir. "Interactions des sérine-protéases avec des supports chromatographiques fonctionnalisés par les amidines." Paris 13, 1990. http://www.theses.fr/1990PA132026.
Trapaidze, Ana. "Integration of thrombin-binding aptamers in point-of-care devices for continuous monitoring of thrombin in plasma." Thesis, Toulouse 3, 2015. http://www.theses.fr/2015TOU30050/document.
Thrombin is the central enzyme in the process of hemostasis. Normally, in vivo concentration of thrombin is rigorously regulated; however, clinically impaired or unregulated thrombin generation predisposes patients either to hemorrhagic or thromboembolic complications. Monitoring thrombin in real-time is therefore needed to enable rapid and accurate determination of drug administration strategy for patients under vital threat. Aptamers, short single-stranded oligonucleotide ligands represent promising candidates as biorecognition elements for new-generation biosensors. The aim of this PhD work therefore is to investigate different solutions for the integration of thrombin-binding aptamers in point-of-care devices for continuous monitoring of thrombin in plasma. The kinetics of aptamer interaction with thrombin and specificity towards prothrombin and thrombin - inhibitor complexes was rigorously investigated using Surface Plasmon Resonance. These experiments unveiled the complex character of interaction of the HD1 with thrombin, confirming nonspecific interactions with prothrombin, natural inhibitors of thrombin, serum albumin whereas another 29-bp aptamer HD22 proved to be highly affine and specific towards thrombin. On the other hand we explored aptamer integration options. We validated the principle and at the same managed to detect different concentrations of thrombin (5-500 nM). We finally proposed a novel approach to increase sensitivity and specificity for thrombin detection based on the engineering of aptadimer structures bearing aptamers HD1and HD22 interconnected with a nucleic acid spacer
Plantier, Jean-Luc. "La thrombine dans la physiopathologie vasculaire : une étude structure-fonction." Université Joseph Fourier (Grenoble), 1994. http://www.theses.fr/1994GRE10179.
Sébert, Morgane. "Les effets de la thrombine sur l'épithélium colique humain, grâce aux organoïdes (modèle ex vivo, 3D)." Thesis, Toulouse 3, 2018. http://www.theses.fr/2018TOU30006/document.
Thrombin, a serine protease known for its role in the coagulation cascade, was described for its effects on the induction of apoptosis in colonic epithelial cell lines, through the activation of Protease Activated Receptors (PARs). However, the effects of thrombin on complex epithelial structures such as the human intestinal epithelium composed of different cell types and cells at different stages of differentiation, has never been investigated. A new cellular model, named organoid, enables to reconstitute a functional epithelium in 3-dimensions (3D), from human resections or biopsies, thanks to the self-renewal and differentiation properties of stem cells isolated from colonic crypts. The first objective of this thesis was to evaluate thrombin's effects on survival, proliferation, apoptosis and differentiation in human colonic epithelium, using the organoid model. Then, we aimed to determining the implication of PAR1 and PAR4 in the thrombin's effects. Thus, thrombin added (at low dose: 10mU/mL and higher dose: 50mU/mL) to organoid cultures from control patients, led to a decrease by half of metabolic activity and cell proliferation. These effects were blocked by the addition of a PAR1 antagonist. Apoptotic process was 8-fold higher in organoid cultures exposed to thrombin (both doses) and this effect was inhibited by the addition of a PAR1 or a PAR4 antagonist. As per epithelial differentiation, thrombin decreased the number of colonospheres (immature structures) favoring the increase of apoptotic structures and colonoids (budding structures considered as more mature). This effect was due to PAR1 and PAR4 activation as again, it was blocked both by PAR1 and PAR4 antagonist. Taken together, these results reveal that exogenous thrombin acts on apoptosis, proliferation and differentiation processes in complex human colonic epithelium. The use of this ex vivo model will allow to compare pathological versus normal organoid cultures, but also to test the effects of pharmacological approaches and new treatment options directly in cultured human tissues. Thus, the 2nd part of this thesis was to setup the best culture conditions and the best imaging conditions to perform a robust and reproducible screening approach, HCS (High-Content Screening), using organoid cultures. Culture conditions in 96-well plates were set up and allowed to acquire images with the HCS system. Operetta HCS coupled to an analysis software (Harmony, PerkinElmer) was used to develop a specific program enabling the recognition of organoids, their counting, their classification according to their differentiation status and enabling to follow organoid growth in cultures. To sum up, the work performed allowed to highlight the effects of thrombin on metabolic status, apoptosis and differentiation of human colon epithelium, using an ex vivo 3D organoid model. The use this model nicely completed epithelial cell line approaches, offering an integrated view of the complex behavior of human epithelium. The HCS approach initiated within this thesis should allow the automated analysis of a number of drugs and treatments. It should help our understanding of epithelial pathologies and the testing of new therapeutic approaches
Daniel, Camille. "Biopuce à aptamères anti-thrombine : exploration d'une technique alternative de détection." Phd thesis, Université de Grenoble, 2013. http://tel.archives-ouvertes.fr/tel-00954086.
Yu, Xiao-Jie. "Chromatographie liquide d'affinité de la thrombine sur résines de polystyrène modifié." Grenoble 2 : ANRT, 1987. http://catalogue.bnf.fr/ark:/12148/cb37610827t.
Quintard, Virginie. "Préparation d'un facteur X* clivable par la thrombine : anti-hémophilique potentiel." Paris 5, 2002. http://www.theses.fr/2002PA05P630.
Tagzirt, Madjid. "Modulation de la production de thrombine et fibrino-formation dans l'hémostase." Paris 5, 2008. http://www.theses.fr/2008PA05P630.
Coagulation factor X (FX) participates in the generation of thrombin, which forms the fibrin network, and activates platelets which release platelet factor 4 (PF4) in large quantities. The first part of this report concerns the characterization of a novel mutant of FX, whose functional defect was deciphered by looking at the phenotype of the patient. We also prepared and characterized five recombinant proteins of thrombin-activable FX. These recombinants restored the amplification of thrombin production in blood plasma of haemophiliacs and could constitute an innovative treatment. For the second part, we investigated the characteristics of PF4 and revealed two unsuspected functions. We found that it prevents the generation of thrombin by inhibiting the activation of the plasma-derived factor V and we demonstrated that PF4 profoundly alters the structure of the fibrin network. These observations provide a new insight on the formation and the structure of the initial platelet clot
Yu, Xiao-Jie. "Chromatographie liquide d'affinité de la thrombine sur résines de polystyrène modifié." Paris 13, 1987. http://www.theses.fr/1987PA132003.
Trumel, Catherine. "Etude des mécanismes biochimiques impliqués au cours de la phase irréversible de l'agrégation plaquettaire." Toulouse 3, 1999. http://www.theses.fr/1999TOU30260.
Buzluca-Dargaud, Gamze Yesim. "Phénotypage du système de coagulation sanguine par la mesure de génération de thrombine : étude pré-clinique et applications cliniques innovantes." Lyon 1, 2006. http://www.theses.fr/2006LYO10122.
Aubert, Hélène. "Mise en évidence du déterminisme génétique du taux plasmatique de TAFI : Etude de la contribution du TAFI au risque thrombotique artériel." Aix-Marseille 2, 2003. http://www.theses.fr/2003AIX22063.
Capot, Rullier Anne. "Thrombine et protéine C activée dans la fibrogénèse et la carcinogénèse hépatiques." Bordeaux 2, 2005. http://www.theses.fr/2005BOR21260.
The aim of this work was to study the role of thrombin and Activated Protein (APC) in liver fibrosis and hepatocellular carcinoma (HCC). We found that KO and heterozygous mice for the main receptor of thrombin, PAR-1, had a reduced susceptibility to CC14-induced fibrosis. In human HCC, liver myofibroblasts and few tumor cells expressed PAR-1. The expression of tissue factor, the main iniitiator of coagulation, was lower in HCC than in non tumoral liver and its expression had no pronostic significance. Finally, PCA, an inhibitor of thrombin generation, had profibrogenic effects in human liver myofibroblasts via PAR-1. Its role is still ill-defined because preincubation with thrombin abolished its effects. PAR-1 could be a promising target for antifibrotic liver treatment. The role of PCA must be addressed in vivo. PAR-1 and tissue factor do not appear as major actors of liver carcinogenesis
Brunette-tournier, Agnès. "Recherche d'une hypercoagulabilité au cours de l'hypertension artérielle pulmonaire." Thesis, Nancy 1, 2010. http://www.theses.fr/2010NAN10133/document.
Pulmonary hypertension (PH) is an affection with an endothelial dysfunction and in situ thromboses. Hypercoagulable state was postulated but was never clearly demonstrated. Our main objective was to determine if patients with idiopathic pulmonary arterial hypertension (iPAH), associated PAH or PH of respiratory diseases had in vitro hypercoagulability with calibrated automated thrombography (CAT). The second objective was to study the endothelial dysfunction in patients with iPAH. We have shown that some patients with iPAH had a hypercoagulable state in vitro. But patients of the other groups had no hypercoagulability. The underlying disease could explain at least in part the difference but it still remain to establish. We have shown that patients with iPAH had an endothelial dysfunction with increase of von willebrand factor, Tissue Factor Pathway Inhibitor and decrease of thrombomodulin
De, Rache Aurore. "Caractérisation électrochimique et spectroscopique de sondes aptamères quadruplexes impliquées dans la détection de la thrombine." Doctoral thesis, Universite Libre de Bruxelles, 2012. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209595.
La deuxième partie du travail a porté sur l’interaction entre les aptamères et le [Ru(NH3)6]3+, fréquemment utilisé pour quantifier des sondes ADN immobilisées. Nos mesures mettent en évidence un comportement électrochimique inédit pour le [Ru(NH3)6]3+ en interaction avec les aptamères. La notion de [Ru(NH3)6]3+ « confiné » a été introduite pour distinguer cette interaction du cas purement électrostatique bien connu. La stœchiométrie d’interaction entre le [Ru(NH3)6]3+ confiné et la partie quadruplexe des séquences d’aptamère a été évaluée à 2 complexes métalliques par quadruplexe et confirmée, en solution, par dichroïsme circulaire (CD). Ces mesures montrent aussi que ce marqueur redox déstabilise la structure quadruplexe anti-parallèle de TBA et que pour les séquences GTA GGT TBA et TTT TTT TBA, il stabilise des structures quadruplexes parallèles. Dans le cas des séquences allongées, l’interconversion entre les structures parallèles et anti-parallèles a été suivie par CD lors d’une compétition ionique entre les cations [Ru(NH3)6]3+ et K+.
Sur base des différentes interactions mises en évidence entre le [Ru(NH3)6]3+ et les aptamères, diverses pistes de détection de la thrombine ont été explorées. Les conditions d’immobilisation des sondes ont été optimisées sur base des dimensions de la thrombine. La détection de cette protéine cible a été réalisée avec succès d’une part en exploitant l’interaction purement électrostatique du [Ru(NH3)6]3+ et d’autre part grâce à la formation de [Ru(NH3)6]3+ confiné.
Doctorat en Sciences
info:eu-repo/semantics/nonPublished
Besbes, Samaher. "Rôle de la Protéine C, un anticoagulant naturel, dans l’association thrombose et cancer." Thesis, Paris 11, 2015. http://www.theses.fr/2015PA11T048/document.
It is now recognized that the invasiveness of tumor cells is not only related to the genotype of these cells but also to their interaction with tumor microenvironment (TM). Within the TM, stromal matrix destabilization promotes tumor progression and metastatic dissemination. The extracellular matrix remodeling is often driven by proteolytic enzymes. However, few studies have investigated the effects of an impairment of the matrix formation. Given these facts and circumstances, we were interested in protein C (PC) and its endothelial receptor (EPCR), as well as in their role in tumorigenesis in leukemia and solid cancers. EPCR is expressed by a wide range of cancer cell lines. It is also detected within the tumor compartment in patients with malignant diseases. EPCR gene is highly conserved but nevertheless contains polymorphisms. One of these SNPs (single nucleotide polymorphism) - 6936A/G – reflects – in the release of a soluble circulating form (EPCRs) resulting from the proteolysis of membrane-associated form. In leukemic patients a high incidence of 6936A/G SNP is observed and associated with thrombosis events. Moreover, EPCR is detected in the majority of tumor biopsies and is abundantly secreted in ascitic fluid. The PC attachment to EPCR and its activation promotes cell survival and migratory potential of tumor cells. Also, APC is able to modulate, by a paracrine manner, interleukins and cytokines secretion. Thus, ovarian cancer cells stimulation by APC induces the synthesis of a functional ovarian thrombopoietin. As this cytokine has a regulatory effect on platelet production, APC may be once again at the interface between hemostasis disorders and coagulation. The elucidation of the intricate role of APC and its endothelial receptor could permit not only to identify new therapeutic approaches but also to prevent cancer-associated thrombosis risk and to decrease morbidity in cancer patients
Forest, Marie-Anne. "Utilisation de la thrombine et de la fibrine pour l'amélioration du succès de greffe de myoblastes chez le patient atteint de dystrophie musculaire de Duchenne." Thesis, Université Laval, 2009. http://www.theses.ulaval.ca/2009/26316/26316.pdf.