Dissertations / Theses on the topic 'P38a'
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Gutierrez, Prat Núria. "Molecular basis of p38a MAPK signaling." Doctoral thesis, Universitat de Barcelona, 2018. http://hdl.handle.net/10803/663438.
Full textRenaud, Emilie. "Inhibition isoforme spécifique des fonctions de la MAPK p38α par des fragments d’anticorps." Thesis, Montpellier, 2018. http://www.theses.fr/2018MONTT088.
Full textMAPK p38α is a key protein in inflammation, but is also involved in many cancer-related processes. All the currently described chemical inhibitors of p38α inhibit its kinase activity by an ATP-competitive mechanism. Because of the high conservation of the ATP-binding pocket, the majority of these inhibitors are not specific to p38α and off-target effects have been reported. To identify alternative approaches to inhibit p38α MAPK, my thesis project focused on the use of scFv antibody fragments as a new highly specific pharmacological tool.Antibody fragments bind to an antigen with high affinity and specificity like conventional immunoglobulins. Their intracellular expression also allows to target cytoplasmic proteins and study the target functions in physiological and pathological processes. Using a naïve library of antibody fragments, we have selected by phage display five scFv specific of MAPK p38α isoform. While all these scFv inhibit the activation of p38α by MMK6, one of them also completely inhibits its kinase activity in vitro. This scFv has a binding site and a mechanism of inhibition distinct from the pharmacological inhibitors currently described: although it does not target the ATP-binding pocket and does not prevent ATP binding, it behaves like a competitive inhibitor of ATP hydrolysis. These results suggest an allosteric effect of this scFv on p38α activity and allow to characterize it as an unconventional competitive inhibitor. The determination of its epitope as well as the confirmation of its inhibitory activity once expressed in the cell cytosol will allow us to propose an alternative approach to target p38α function using antibody fragments.These data open up new perspectives for the design of more specific p38α chemical inhibitors than those currently available
Visseq, Alexia. "Conception et synthèse d’inhibiteurs sélectifs de protéines kinases pour le traitement de l’allodynie mécanique." Thesis, Université Clermont Auvergne (2017-2020), 2019. http://www.theses.fr/2019CLFAC048.
Full textChronic pain is a global public health priority which affects more than 20% of Europeans. Mechanical allodynia, a pain in response to normally innocuous stimuli, is one of the most prevalent pain symptoms. Despite intensive research toward the study of pain mechanisms, currently available treatments of pain are not always effective, and can produce side-effects. In this context, the aim of the project is to design, synthesize and evaluate selective inhibitors of protein kinases for the treatment of mechanical allodynia. During this PhD work, new selective inhibitors of the protein kinase p38α has been discovered. This protein kinase is known for its implication in chronic pain and mechanical allodynia. A structure-activity relationship study was performed to identify the important structural features allowing a gain of activity of molecules in vitro and in vivo using an animal model. The best compounds showed submicromolar IC50 values toward p38α and a strong inhibition of mechanical allodynia in vivo
Vitos, Faleato Jessica. "Role of p38α in lung tumor progression." Doctoral thesis, Universitat de Barcelona, 2018. http://hdl.handle.net/10803/462107.
Full textLos tumores evolucionan al adquirir anormalidades genéticas de manera secuencial, como la activación de K-Ras y la pérdida de funcionalidad de Tp53, que permiten a las células transformadas sobrevivir, proliferar, e invadir, así como acondicionar su microambiente. Simultáneamente, las células transformadas también han de lidiar con situaciones de estrés, incluyendo un metabolismo acelerado, un genoma altamente inestable, o el sistema de vigilancia de las células inmunes. Por lo tanto, las células cancerosas han de apoyarse en vías de señalización no-oncogénicas que les permiten tolerar las deficiencias en los sistemas de control de homeostasis, adaptarse a los nuevos requerimientos funcionales, y monitorizar los cambios en el microambiente para responder de manera apropiada. La vía de las p38 MAPK está íntimamente relacionada con la respuesta al estrés y es utilizada por las células para transducir señales extracelulares y orquestrar las respuestas correspondientes. p38α es el miembro de la familia de p38 MAPK más ampliamente expresado, y se le han atribuido clásicamente funciones supresoras tumorales gracias a su habilidad para detener el ciclo celular, inducir diferenciación, y desencadenar procesos apoptóticos. No obstante, hay evidencia de que el nivel de actividad de p38 MAPK podría estar incrementado en varios tipos de tumor humanos y, en algunos casos, se ha correlacionado con una baja supervivencia, lo que sugiere un papel pro-tumoral. En este estudio, hemos observado una correlación negativa entre los niveles de expresión de p38α y la supervivencia en pacientes de adenocarcinoma pulmonar. Hemos usado un modelo murino de cáncer de pulmón inducido por la expresión del oncogén K-Ras para demostrar que, efectivamente, p38α juega un papel dual durante el desarrollo de la carcinogénesis de pulmón. Por una parte, p38α evita la transformación maligna de las células pulmonares epiteliales sanas mediante la inducción de diferenciación celular. Sin embargo, en las células epiteliales pulmonares transformadas, p38α estimula la proliferación y la secreción de citocinas inflamatorias que preparan un nicho favorable para la progresión tumoral. p38α también juega un rol pro-tumorigénico al promover la vascularización del tumor y la immunotolerancia por parte de las células mieloides infiltradas. En conjunto, nuestros datos sugieren que la inhibición de esta vía de señalización podría ser útil en términos terapéuticos para los casos de adenocarcinoma de pulmón.
Thapa, Dibesh. "Targeting the interaction between p38α and TAB1." Thesis, King's College London (University of London), 2017. https://kclpure.kcl.ac.uk/portal/en/theses/targeting-the-interaction-between-p38-and-tab1(9b1a1609-805a-4698-a673-2a686dabf905).html.
Full textMäkelä, Kimmo K. "Characterization and performance of electrorheological fluids based on pine oils /." Espoo, Finland : University of Oulu, 1999. http://www.vtt.fi/inf/pdf/publications/1999/P385.pdf.
Full textHeikkilä, Anna-Mari. "Inherent safety in process plant design : an index-based approach /." Espoo [Finland] : Technical Research Centre of Finland, 1999. http://www.vtt.fi/inf/pdf/publications/1999/P384.pdf.
Full textUosukainen, Seppo. "JMC method applied to active control of sound : theoretical extensions and new source configurations /." Espoo [Finland] : Technical Research Centre of Finland, 1999. http://www.vtt.fi/inf/pdf/publications/1999/P386.pdf.
Full textPatil, Ashok R. "High power shunt regulation of spacecraft solar arrays." Diss., Virginia Tech, 1995. http://hdl.handle.net/10919/40216.
Full textPatterson, Douglas T. "Tribopolymerization as an approach to two-stroke engine lubrication." Thesis, This resource online, 1995. http://scholar.lib.vt.edu/theses/available/etd-01312009-063142/.
Full textPlamondon, Philippe. "La MAP kinase p38γ influence la structure des cardiomyocytes." Mémoire, Université de Sherbrooke, 2014. http://savoirs.usherbrooke.ca/handle/11143/5307.
Full textArabacilar, Pelin. "Investigating the mechanisms of p38 activation." Thesis, King's College London (University of London), 2016. http://kclpure.kcl.ac.uk/portal/en/theses/investigating-the-mechanisms-of-p38-activation(ae0beac3-0bab-4ae6-b91a-ef9f8fb9b9ff).html.
Full textTasker, Alexander John. "Processes of hybrid knowledge creation in pastoralist development." Thesis, University of Sussex, 2018. http://sro.sussex.ac.uk/id/eprint/80671/.
Full textCánovas, Bilbao Begoña. "Role of p38 MAPK in breast cancer." Doctoral thesis, Universitat de Barcelona, 2017. http://hdl.handle.net/10803/405893.
Full textLa proteína quinasa p38α está considerada como un supresor tumoral. Sin embargo, estudios recientes sugieren que puede promover el crecimiento y la supervivencia en algunos tipos de células tumorales, así como que su inhibición coopera con determinados agentes quimioterapéuticos. Así pues, la función de p38α parece depender tanto del tipo de célula como del contexto. Por ello, este trabajo abordó el papel de p38α en el contexto concreto de la progresión del cáncer de mama. Usando el modelo “Polyoma middle T” (PyMT), hemos observado que la expresión de p38α en las células epiteliales que conforman el tumor es esencial para el crecimiento del mismo. Para analizar los mecanismos moleculares implicados establecimos un sistema ex vivo consistente en líneas celulares derivadas de tumores inducidos por PyMT. Observamos que en ausencia de p38α estas células mostraban estrés replicativo, un mayor daño en el ADN y un incremento en los errores de segregación que correlacionaban con una menor viabilidad celular. Los defectos durante la replicación y el aumento en el daño en el ADN nos llevaron a investigar el estado de la ruta de respuesta al daño en el ADN. Así pues, encontramos que las células deficientes en p38α mostraban defectos en la generación de ADN monocatenario, en la activación de ATR y en el reclutamiento de RAD51 a los focos de daño, lo que sugería que la reparación de ADN por recombinación homóloga estaba afectada. Además identificamos CtIP, un factor esencial para la resección del ADN, como sustrato directo de p38α. La desregulación de CtIP influiría negativamente en la respuesta al daño en el ADN y explicaría en gran medida los fenotipos descritos anteriormente. En conjunto, nuestros datos sugieren que p38α es necesaria para una eficiente reparación y replicación del ADN y por tanto para el mantenimiento de la estabilidad cromosómica en las células epiteliales de cáncer de mama. Los resultados anteriores sugerían que la intervención farmacológica de p38α podría incrementar la sensibilidad a agentes inductores de inestabilidad cromosómica como los taxanos. Confirmamos esta teoría usando el modelo PyMT y xenografías derivadas de pacientes, comprobando que en ambos casos la inhibición de p38α potenció, aceleró o prolongó el efecto anti-tumoral de los taxanos paclitaxel y docetaxel.
Davies, Gareth. "Folding of p38 mitogen-activated protein kinase." Thesis, University of Warwick, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.412847.
Full textJones-Phillips, Dominic. "A role for p38δ MAPK in the pathogenesis of rheumatoid arthritis." Thesis, University of Leeds, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.634754.
Full textDan, Yuzhen 1992. "Signaling networks regulated by the kinase p38α in cancer cell homeostasis." Doctoral thesis, TDX (Tesis Doctorals en Xarxa), 2022. http://hdl.handle.net/10803/673710.
Full textp38α (codificada por el gen MAPK14) es una proteína reguladora crucial en las respuestas celulares a casi todos los tipos de estrés tanto provenientes del ambiente extracelular como del interior de la célula. Una vez activada, p38α fosforila varios sustratos en el citoplasma y en el núcleo, lo que permite que esta vía regule una amplia variedad de procesos celulares, que incluyen la proliferación, la diferenciación o la supervivencia celular. Dado la gran cantidad de funciones que pueden ser controladas por p38α, en este trabajo realizamos análisis proteómicos y fosfoproteómicos para estudiar las redes de señalización reguladas por p38α en las células tumorales en homeostasis. Nuestro estudio ha identificado 35 proteínas y 114 sitios de fosforilación que son modulados por p38α, así como la importancia de otras vías de señalización por quinasas, como MK2 y mTOR, en las funciones reguladas por p38α. Además, el análisis funcional del (fosfo)proteoma ha revelado que p38α participa en la regulación de la adhesión celular, la replicación del ADN y el procesamiento del ARN. También mostramos que p38α regula negativamente la adhesión célula-célula, lo que probablemente está mediado por la modulación transcripcional de ArgBP2. En conjunto, nuestros resultados ilustran la complejidad de las redes de señalización reguladas por p38α, proporcionan información valiosa sobre las fosforilaciones dependientes de p38α en células tumorales y documentan un mecanismo por el que p38α regula la adhesión célula-célula durante la homeostasis de las células tumorales.
Delplanque, Sylvain. "Information émotionnelle et composantes évoquées P3a et P3b." Paris 6, 2004. http://www.theses.fr/2004PA066085.
Full textPethel, Michele Lee. "Plasmid-influenced changes in Mycobacterium avium catalase activity." Thesis, Virginia Tech, 1988. http://hdl.handle.net/10919/43266.
Full textMaster of Science
Pelletier, Carole. "Une approche philosophique, hétéropolitique et féministe de la vieillesse." Doctoral thesis, Université Laval, 2005. http://hdl.handle.net/20.500.11794/43815.
Full textPaillas, Salomé. "Étude des mécanismes de résistance à l’Irinotécan dans le cancer colorectal : implication de la MAPK p38." Thesis, Montpellier 2, 2011. http://www.theses.fr/2011MON20058/document.
Full textDespite the recent advances achieved in the treatment of colon cancer, tumor resistance is a frequent cause of chemotherapy failure. This work was aimed to determine the molecular mechanisms involved in the resistance to Irinotecan, an anticancer agent widely used in colorectal cancer treatment. We have demonstrated that the α and β forms of p38 MAPK were involved in this resistance. Moreover, we have correlated less phospho-p38 in colon cancer primary tumor of patients sensitive to Irinotecan-based treatment, compared to non responder patients. During the project, we aimed to determine the role of p38 MAPK in the processes of autophagy in colorectal cancer cells, and their impact in Irinotecan cytotoxicity. We have shown that p38 induced survival autophagy in p53 deficient cells. Then, we have shown that autophagy inhibition increased the SN38 cytotoxicity (active metabolite of Irinotecan) in p53 deficient cell lines. Finally, we have studied the role of p38 MAPK in lipid metabolism in p53 deficient cells. All these findings highlight new ways of research to identify the molecular mechanisms involved in chemoresistance as well as new pharmacological approaches to overcome the resistance
Rahal, Pamela. "Role of GSK3β - MLK3 - p38γ MAPK Signalling in Satellite Cell Proliferation Regulation." Thesis, Lyon, École normale supérieure, 2015. http://www.theses.fr/2015ENSL1000.
Full textMLK3 is a Ser/Thr MAP3K, which activates MAPKs signalling pathways in different cell types. The Ser/Thr kinase GSK3-β directly phosphorylate Ser 792 residue and activate MLK3. Since neither the role of MLK3, nor GSK3-β -MLK3 interaction have been previously investigated in muscle, the aim of my thesis was to elucidate their contribution in the regulation of muscle mass and physiology.Skeletal muscle post-natal growth and adult regeneration relies on satellite cell-mediated myonuclear accretion, during which, activated satellite cells, proliferate, differentiate and fuse with preexisting myotubes.I have demonstrated that in skeletal muscle, GSK3-β acts upstream of MLK3 to induce satellite cells proliferation through the induction of MLK3-p38γ MAPK signalling. Similarly, in vivo CTX-induced TA damage in MLK3 KO mice resulted in decreased number of proliferating Pax7+/ki67+ satellite cells, with a rapid muscle regeneration ability.These data suggest provide a yet unknown role of MLK3 in skeletal muscle tissue that could help in curing age-related muscle dystrophies
Sundaresan, Pavithra. "Platelet collagen receptors and regulation of p38 MAP kinase." Thesis, University of Cambridge, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.619577.
Full textGaffey, Kate. "Glucocorticoid resistance in COPD : the role of p38 MAPK." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/glucocorticoid-resistance-in-copd-the-role-of-p38-mapk(9c60954b-f891-4f8b-8004-825e6d173503).html.
Full textFortier, Manon. "Rôle de la MAP kinase p38α au cours d'une agression aiguë du foie Hepatospecific ablation of p38α governs the inflammatory response to promote efficient tissue repair during acute liver injury." Thesis, Sorbonne Paris Cité, 2018. http://www.theses.fr/2018USPCB100.
Full textTo prevent acute liver injuries induced by viral hepatitis, toxins or drug overload, liver activates different interconnected processes such as proliferation, inflammation or cell death. Interestingly, one protein is at the crossroad of these pathways: the MAP (Mitogen Activated Protein) kinase p38 alpha. Several studies showed a dual role for the p38a mitogen-activated protein kinase pathway in liver. Even if its role as a negative regulator of hepatocyte proliferation has been largely described, p38a may also harbor an oncogenic role involving cancer related-processes and notably inflammation. However, its function during an acute injury, in adult liver, remains uncharacterized. My thesis aim was to characterize p38 alpha MAP Kinase role during an acute liver injury thanks to a mouse model with a conditional hepatocyte specific deletion of p38a (KO model). To that end, we used an experimental hepatopathy system classically used to reproduce hepatocyte division in inflammatory context: the carbon tetrachloride model (CCl4). An injection of this hepatotoxic in mice induces hepatocyte cytolysis in centrilobular zone rapidly followed by immune cell infiltration and compensatory healthy hepatocyte proliferation to repair hepatic tissue. Control (CT) and KO mice were sacrificed at different timings after injection to establish a post-CCl4 kinetic, during which blood and liver tissue were collected. Liver injuries, inflammation, apoptosis and proliferation processes were then assayed. First, absence of p38a decreases hepatocyte number into cell cycle S phase (BrdU labelling, CyclinA2 levels) during regenerative process post-CCl4. Interestingly, we showed that p38a deficiency confers a protective effect against hepatic injuries induced by CCl4. Indeed, cytolysis areas and alanine transaminase levels (hepatocyte death reflection) were significantly decreased (40H to 60H post-CCl4) in KO mice. To explain this phenotype, we investigated apoptosis pathway during regenerative kinetic, but our results did not show any significant differences between CT and KO mice. On the other hand, antioxidant response is increased in KO livers and could therefore be involved in the hepatic tissue protection. Finally, immunohistochemistry analysis showed a massive inflammatory cell recruitment to cytolysis areas correlated with a significant increase of cytokines (as TNFa) and pro-inflammatory chemokines (as CCL2 and CCL5). These data strongly suggest that p38a deficiencies mediate a specific immune response to favor hepatic tissue clearance and repair. In conclusion, my thesis work shows that the absence of p38a MAP Kinase is hepatoprotective during an acute liver injury enhancing "proliferation - inflammatory response" balance, therefore promoting early tissue repair and maintaining liver homeostasis
Marais, Erna. "Role of cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP) and p38 mitogen activated protein kinase (p38 MAPK) in preconditioning of the ischaemic myocardium." Thesis, Stellenbosch : Stellenbosch University, 2002. http://hdl.handle.net/10019.1/53039.
Full textENGLISH ABSTRACT: Ischaemic preconditioning (PC) is the phenomenon whereby a short episode of coronary occlusion followed by reperfusion protects the myocardium against a subsequent period of prolonged (also called index or sustained) ischaemia. Even though the exact mechanism of PC remains to be established, it implies that the heart has an endogenous protective mechanism against ischaemia which, if identified, may have important clinical implications. The importance of establishing the mechanism of PC lies in the potential to convert this biological phenomenon into a therapeutic modality to be used clinically. If mediated by certain components of a signal transduction pathway, such a goal will be achievable. Several triggers and signal transduction pathways have been implicated in the mechanism of protection induced by PC: for example, receptor-dependent endogenous triggers (such as adenosine and opioids) and receptor-independent endogenous triggers (such as free radicals and calcium). However, the involvement of both the ~-adrenergic signalling pathway as well as nitric oxide (NO) in PC has not been defined. It has been suggested that all triggers are linked to a common final pathway, for example, activation of protein kinase C (PKC) and/or the mitogen-activated kinases (MAPKs), in particular p38 MAPK. However, the role of the latter is still controversial. The aim of this study was to: (A) characterize changes in the cyclic nucleotides, cAMP and cGMP, and p38 MAPK occurring during the entire experimental procedure in an attempt to gain insights into the possible mechanisms involved in ischaemie PC (Chapter 3); (8) establish the significance of the changes observed in cAMP and cGMP by pharmacological manipulation of their respective pathways (Chapters 4 and 5); (C) establish the role of p38 MAPK in ischaemie PC: trigger or mediator involvement (Chapter 6). Isolated perfused working rat hearts were preconditioned by 3 x 5 min global ischaemia, interspersed by 5 min reperfusion, followed by 25 min global ischaemia and 30 min reperfusion. Functional recovery during reperfusion was used as end-point. Hearts were freeze-clamped at different times during the PC protocol, sustained ischaemia, as well as during reperfusion. Tissue cyclic nucleotides (cAMP and cGMP), cyclic nucleotide phosphodiesterase (cAMP- and cGMP-PDE) activities, adenylyl cyclase and protein kinase A activities and p-adrenergic receptor characteristics were determined. p38 MAPK activation was also assessed by Western blotting, using dual phospho-p38 MAPK (Thr180ITyr182) antibody as well as activating transcription factor 2 (ATF2) activation. In addition, to evaluate the role of p38 MAPK in PC protection, the effect of inhibition of p38 MAPK activation, by 8B203580, was determined in adult isolated rat cardiomyocytes as well as in isolated perfused rat hearts. Based on the results obtained, it is proposed that during a multi-cycle ischaemie PC protocol triggers (presumably endogenous catecholamines and NO) are released which induce cyclic changes in cyclic nucleotides, cAMP and cGMP. Both these cyclic nucleotides transiently activate the downstream stress kinase, p38 MAPK, which may trigger further downstream adaptive processes. Furthermore, the sustained ischaemic period of PC hearts was characterized by attenuated cAMP and elevated cGMP levels, as well as attenuated activation of p38 MAPK, which was associated with cardioprotection. In addition, pharmacological attenuation of p38 MAPK activation during sustained ischaemia led to functional recovery. It is concluded that the cardioprotection of PC is due to attenuation of ischaemia-induced p38 MAPK activation. Pharmacological manipulation of this kinase should be considered as a therapeutic modality in the future.
AFRIKAANSE OPSOMMING: Isgemiese prekondisionering (PK) verwys na die verskynsel waardeur 'n kort, verbygaande episode van isgemie gevolg deur herperfusie, die miokardium teen 'n daaropvolgende langdurige periode van isgemie beskerm. Die presiese meganisme van beskerming van PK moet nog opgeklaar word, maar dit impliseer dat die hart oor 'n endogene beskermingsmeganisme beskik wat, indien geïdentifiseer, belangrike kliniese implikasies mag hê. Die belang van opklaring van die meganisme van PK lê daarin dat 'n biologiese verskynsel in 'n terapeutiese modaliteit vir kliniese gebruik, omgeskakel kan word. Sou dit deur bepaalde komponente van 'n seintransduksiepad gemedieër word, is so 'n doel bereikbaar. Verskeie stimuli en seintransduksiepaaie is in PK betrokke: byvoorbeeld, reseptorafhanklike endogene stimuli (soos adenosien en opioïde), asook reseptor-onafhanklike endogene stimuli (soos vrye radikale en kalsium). Die betrokkenheid van die padrenerge seintransduksiepad asook stikstofoksied (NO) in PK egter nog nie behoorlik evalueer nie. Dit is voorgestel dat alle stimuli op 'n finale algemene pad uitloop, soos byvoorbeeld die aktivering van protein kinase C (PKC) en/of die mitogeen-geaktiveerde kinases (MAPKs), spesifiek die p38 MAPKs. Laasgenoemde se rol in PK is steeds kontroversieël. Die doel van die studie was dus: (A) karakterisering van die veranderinge in die sikliese nukleotiede, cAMP en cGMP, en p38 MAPK wat tydens die hele eksperimentele prosedure plaasvind, in 'n poging om meer insig te verkry aangaande moontlike meganismes betrokke in isgemiese PK (Hoofstuk 3); (8) bepaling van die belang van die waargenome veranderinge in cAMP en cGMP deur hulonderskeie paaie farmakologies te manipuleer (Hoofstukke 4 en 5); (C) bepaling van die rol van p38 MAPK in PK: betrokkenheid as stimulus of mediator (Hoofstuk 6). Geïsoleerde, geperfuseerde werkende rotharte is geprekondisioneer deur blootstelling aan 3 x 5 min globale isgemie, afgewissel met 5 min herperfusie, gevolg deur 25 min globale isgemie en 30 min herperfusie. Funksionele herstel tydens herperfusie is as eindpunt gebruik. Harte is op verskillende tye tydens die PK protokol, volgehoue isgemie, asook herperfusie gevriesklamp. Weefsel sikliese nukleotiede (cAMP en cGMP), die aktiwiteit van sikliese nukleotied fosfodiesterases (cAMP- en cGMP-PDE), adeniel siklase en protein kinase A (PKA) asook die eienskappe van die p-adrenerge reseptor is gemeet. p38 MAPK aktivering is met Westerse oordragtegnieke bepaal, deur van dubbel gefosforileerde p38 MAPK (Thr180fTyr182) antiliggame asook geaktiveerde transkripsie faktor 2 (ATF2) gebruik te maak. Die rol van p38 MAPK in PK beskerming is evalueer deur die effek van inhibisie van p38 MAPK aktivering met SB 203580, in volwasse geïsoleerde rot kardiomiosiete asook in geïsoleerde geperfuseerde rotharte, te bepaal. Na aanleiding van die resultate, is voorgestel dat, tydens 'n multi-siklus isgemie PK protokol, stimuli (moontlik endogene katekolamiene en NO) vrygestel word wat die sikliese veranderinge in sikliese nukleotiede, cAMP en cGMP, veroorsaak. Beide hierdie sikliese nukleotiede aktiveer die distale stres kinase, p38 MAPK, op 'n betekenisvolle, maar verbygaande manier. Hierdie kinase mag verdere distale aanpassingsprosesse stimuleer. Die volgehoue isgemiese periode van PK harte is gekenmerk deur verminderde cAMP en verhoogde cGMP vlakke, asook verminderde aktivering van p38 MAPK. Hierdie veranderinge is met beskerming van die hart teen isgemie geassosieer. Daarbenewens, farmakologiese vermindering van p38 MAPK aktivering tydens volgehoue isgemie het tot verbeterde funksionele herstel gelei. Die gevolgtrekking is gemaak dat die beskermende effek van PK die gevolg is van verminderde aktivering van isgemies-geïnduseerde p38 MAPK. Farmakologiese manipulasie van hierdie kinase moet in die toekoms as terapeutiese modaliteit oorweeg word.
Ferreiro, Neira Isabel. "Transcriptional regulation by the mammalian stress-activated protein kinase p38." Doctoral thesis, Universitat Pompeu Fabra, 2011. http://hdl.handle.net/10803/80661.
Full textLa regulación de la transcripción por las Proteínas Quinasas activadas por Estrés (SAPKs) es un aspecto esencial para la adaptación a los estímulos extracelulares. En mamíferos, la activación de la SAPK p38 da lugar a la regulación de la expresión génica a través de la fosforilación de varios factores de transcripción. Sin embargo, cómo p38 SAPK regula el programa de expresión génica de adaptación al estrés así como los mecanismos utilizados por la SAPK permanece sin caracterizar. Los resultados presentados en este manuscrito muestran que p38 SAPK juega un rol central en la regulación de la expresión génica en respuesta a estrés, ya que hasta el 80% de los genes inducidos son dependientes de p38 SAPK. También observamos que en respuesta a cada tipo de estrés se induce un grupo de genes específicos, y sólo hay una pequeña respuesta de genes comunes a los diferentes tipos de estrés la cual engloba principalmente factores de transcripción. Además, hemos observado que para regular la transcripción, p38 se recluta a los promotores de respuesta a estrés a través de su interacción con factores de transcripción. Asimismo, la actividad de p38 permite el reclutamiento de la RNA Polimerasa II y de la MAPKK MKK6 a los promotores inducidos por estrés. La presencia de p38 activa en las regiones codificantes sugiere su participación durante la elongación. En conjunto, los resultados mostrados en este manuscrito establecen a p38 como un regulador esencial de la transcripción en respuesta a estrés, así como definen nuevas funciones de p38 en la regulación de la transcripción en respuesta a estrés.
Wieland, Andreas [Verfasser]. "Funktion der p38 mitogenaktivierten Proteinkinase in kultivierten Pankreaskarzinomzellen / Andreas Wieland." Ulm : Universität Ulm. Medizinische Fakultät, 2014. http://d-nb.info/1049561392/34.
Full textNiswander, Julie M. "Molecular Correlates of Adaptation and Apoptosis: p38 Signaling in Hippocampus." University of Toledo Health Science Campus / OhioLINK, 2004. http://rave.ohiolink.edu/etdc/view?acc_num=mco1085678685.
Full textRoger, Séverine. "Implication des MAP Kinases ERK2 et p38 dans l'activation plaquettaire." Paris 7, 2005. http://www.theses.fr/2005PA077165.
Full textSakurai, Kenji. "Cutaneous p38 mitogen-activated protein kinase activation triggers psoriatic dermatitis." Doctoral thesis, Kyoto University, 2020. http://hdl.handle.net/2433/245835.
Full text0048
新制・課程博士
博士(医学)
甲第22150号
医博第4541号
新制||医||1039(附属図書館)
京都大学大学院医学研究科医学専攻
(主査)教授 竹内 理, 教授 稲垣 暢也, 教授 杉田 昌彦
学位規則第4条第1項該当
Doctor of Medical Science
Kyoto University
DFAM
Loonat, Aminah Ahmed. "The involvement of p38 gamma MAPK in pathological cardiac hypertrophy." Thesis, King's College London (University of London), 2016. http://kclpure.kcl.ac.uk/portal/en/theses/the-involvement-of-p38gamma-mapk-in-pathological-cardiac-hypertrophy(f00e26a7-dab2-474d-9d3e-a52dfe9e873e).html.
Full textDomeyer, David. "Docking-basiertes virtuelles Wirkstoff-Design von p38 MAP Kinase-Inhibitoren /." [S.l. : s.n.], 2005. http://www.gbv.de/dms/bs/toc/52427083X.pdf.
Full textNiswander, Julie Marie. "Molecular correlates of adaptation and apoptosis : p38 signaling in hippocampus." Connect to full-text via OhioLINK ETD Center, 2004. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=mco1085678685.
Full text"In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Medical Sciences." Major advisor: Linda A. Dokas. Document formatted into pages: iv, 150 p. Title from title page of PDF document. Bibliography: pages 44-52.
Bruns, Svenja Anne [Verfasser]. "Autophagy regulation by the p38 MAP kinase / Svenja Anne Bruns." Magdeburg : Universitätsbibliothek, 2017. http://d-nb.info/1128726491/34.
Full textWissing, Erin R. "Uncovering the complexity of muscular dystrophy pathology through disease signaling." University of Cincinnati / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1393236115.
Full textDietrich, Justin David. "The Design, Synthesis, and Evaluation of Novel DFG-out Allosteric Kinase Inhibitors." Diss., The University of Arizona, 2008. http://hdl.handle.net/10150/195661.
Full textYoussif, Catrin. "Myeloid p38 MAPK signaling in intestinal homeostasis, inflammation and tumorigenesis = Señalización por la MAPK p38 de células mieloides en la homeostasis, inflamación y tumorogénesis intestinal." Doctoral thesis, Universitat de Barcelona, 2017. http://hdl.handle.net/10803/462108.
Full textLazarus, Philip. "Mechanism of decrease of protein synthesis by sodium cyanate in murine P388 leukemia cells." Thesis, McGill University, 1987. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=75367.
Full textPatel, Niranjan M. "Multicomponent network and linear polymer systems : thermal and morphological characterization /." Diss., This resource online, 1990. http://scholar.lib.vt.edu/theses/available/etd-07122007-103930/.
Full textPascual, Vincent D. "The conceptual design and evaluation of an accuracy control system to support the hull construction of aircraft carriers." Master's thesis, This resource online, 1991. http://scholar.lib.vt.edu/theses/available/etd-01122010-020056/.
Full textLeipelt, Juliano. "Avaliação in vitro do potencial biológico de Myrciaria plinioides (D. Legrand) em células tumorais." reponame:Repositório Institucional da UNIVATES, 2016. http://hdl.handle.net/10737/1110.
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O câncer é apontado como a segunda maior causa de morte em todo o mundo, com previsão de em breve ser tornar a primeira. O câncer de próstata está entre os 5 tipos de câncer mais diagnosticados em homens, sendo que o câncer hepático está em segundo lugar em taxa de mortalidade entre homens e mulheres. Indícios apontam para uma ativação das vias da inflamação associados a uma inibição das vias de morte celular no processo de carcinogênese. A regulação destas vias torna-se alvo importante e complementar no controle do câncer, sendo estimulada a busca de biomoléculas com este potencial. As plantas são importante fonte de descoberta de novas biomoléculas com ampla utilização para o tratamento de diversas patologias. A família Myrtaceae possui diversas espécies que são apontadas como fortes candidatos em potencial nesta busca, incluindo as do gênero Myrciaria. A espécie Myrciaria plinioides não possui estudos referentes suas propriedades terapêuticas ou a atuação em vias de sinalização envolvidas na inflamação ou na carcinogênese. Neste contexto, este estudo teve por objetivo avaliar a atividade do extrato etanólico de M. plinioides em células de carcinoma hepatocelular (HepG2) e próstata (LNCaP) , através da análise de expressão dos marcadores p38-α, pp38-α, NF-κB e caspase-3, envolvidos na carcinogênese, e o efeito sobre a viabilidade celular através do método de MTT. A viabilidade das células foi alterada significativamente, em ambas as linhagens celulares quando tratadas com o extrato etanólico. A análise da expressão proteica demonstra significativa inibição da expressão de p38-α e caspase-3 nas células LNCaP, quando tratadas com extrato etanólico de M. plinioides seguido de LPS. Em células HepG2, somente houve alteração na expressão da caspase-3 na concentração de 200 μg/mL, com ou sem adição de LPS após tratamento com extrato. Os resultados deste estudo demonstraram redução da viabilidade celular nas duas linhagens tumorais, expressão diferenciada de proteínas envolvidas em apoptose, o que leva a indícios da ativação de mecanismos distintos pelo extrato em cada tipo celular. Estudos futuros para averiguar o mecanismo celular e a indução de morte em células tumorais de câncer de próstata e de fígado podem contribuir para a identificação e elucidação de novas biomoléculas com potencial antitumoral.
Cancer is touted as the second leading cause of death worldwide, forecast to soon be making the first. Prostate cancer is among the five most cancers diagnosed in men, and liver cancer is second in mortality between men and women. Evidence points to the activation of pathways of inflammation associated with an inhibition of cell death pathways in carcinogenesis. The regulation of these pathways becomes important and complementary target in cancer control, and stimulated the search for biomolecules with this potential. The plants are important source of discovery of new biomolecules with wide use for the treatment of various diseases. The Myrtaceae family has many species that are identified as potential candidates strong in this search, including the Myrciaria genre. The species Myrciaria plinioides not have studies on its therapeutic properties or performance in signaling pathways involved in inflammation or carcinogenesis. In this context, this study aimed to evaluate the activity of the ethanol extract of M. plinioides in hepatocellular carcinoma cells (HepG2) and prostate (LNCaP) by expression analysis of p38-α markers, PP38-α, NF-kB and caspase-3, involved in carcinogenesis, and the effect on cell viability by the MTT method. The viability of cells was significantly altered in both cell lines when treated with ethanolic extract. Protein expression analysis demonstrates significant inhibition of p38-α expression and caspase-3 in LNCaP cells, when treated with ethanolic extract of M. plinioides followed by LPS. In HepG2 cells there was only a change in the expression of caspase-3 at a concentration of 200 / ml, with or without addition of LPS after treatment with extract. The results showed reduction of cell viability in both tumor lines, differential expression of proteins involved in apoptosis, leading to evidence of activation by distinct mechanisms in each extract cell type. Further studies to investigate the cellular mechanism, and induction of death in tumor cells of prostate and liver cancer may contribute to the identification and elucidation of new biomolecules with antitumor potential.
Paul, Anton Dilojaan. "Electrocatalytically induced liberation of mineral matter from coal." Diss., Virginia Polytechnic Institute and State University, 1988. http://hdl.handle.net/10919/82636.
Full textPh. D.
Barbosa, Bruna Zelante. "Comprometimento funcional de células dendríticas derivadas de monócitos de pacientes com câncer: envolvimento das vias de sinalização p38 e ERK1/2 (p44/p42) MAPK." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/42/42133/tde-10052017-150608/.
Full textDendritic cells are the main presenting cells and present alterations in cancer patients. The signaling pathways p38 and ERK1/2 MAPK participate of monocyte-derived dendritic cells (Mo-DCs) differentiation. Exposition to MCF-7s supernatant (TS) decreased CD14 and CD1a expression (frequency) while enhanced IL-6 and IL-10 production. Inhibition of ERK1/2 MAPK reverted CD14 expression and partially reverted cytokines production. Inhibition of p38 MAPK reverted CD1a and CD14 expression and partially reverted cytokines production too. We identified the heat shock protein HSP27. Exposition to HSP27 did not cause the observed alterations seen when the cells were exposed to TS. Lastly, treatment of Mo-DCs from breast cancer patients with the p38 inhibitor decreased CD86 and HLA-DR expression. Therefore, the data presented in this study suggest that p38 MAPK inhibition does not appear to be an interesting approach in the manipulation of Mo-DCs from breast cancer patients.
Anerillas, Aljama Carlos. "Caracterización de la senescencia celular inducida por Sprouty: papel de p38." Doctoral thesis, Universitat de Lleida, 2019. http://hdl.handle.net/10803/666058.
Full textLos miembros de la familia de proteínas Sprouty han sido clásicamente descritos como inhibidores de la señalización iniciada por los receptores tirosina quinasa, siendo por ello reiteradamente propuestos como supresores tumorales. Por otro lado, la senescencia celular es una respuesta a ciertos niveles de estrés en la que las células deciden abandonar su capacidad proliferativa y secretar un amplio abanico de factores para influir sobre el entorno próximo. Trabajos previos demuestran que Spry1 promueve la inducción de senescencia celular tanto en tiroides como en el desarrollo de la vagina de manera independiente a su acción clásica sobre los receptores tirosina quinasa. En la presente tesis hemos expandido la implicación de Spry1 en senescencia a paradigmas en los que ésta es relevante como el envejecimiento, la reparación de tejidos o la senescencia asociada a quimioterapia. Además, hemos desvelado que Spry1 responde al estrés oxidativo potenciando la vía p38. Por tanto, los resultados expuestos confirman a las proteínas Spry como mediadores generales de la senescencia celular.
Members of Sprouty family of genes (Spry1-4) have been classically assumed to be inhibitors of signaling initiated by receptor tyrosine kinases. As such, they have been proposed as tumor suppressor genes. On the other hand, cellular senescence is a response in front of different cellular stresses in which cells decide to cease their proliferation. Moreover, senescent cells implement the secretion of a myriad of factors to influence their proximal environment. Previous data from our group demonstrate that Spry1 promotes cellular senescence in the thyroid gland and in vaginal development, but in an ERK-independent manner. The present work expands the implications of Spry genes to other cellular senescence scenarios such as age-related and regeneration-related senescence. Surprisingly, Spry1 induction in the senescent response is controlled by oxidative stress. Mechanistically, Spry proteins enhance p38 MAPK activation required for the proper induction of most of the traits of cellular senescence. Hence, these results confirm Spry genes as novel, general mediators of cellular senescence.
Sarafraz, Shekary Negin. "Contribution of p38 mitogen-activated protein kinase isotypes to cardiac physiology." Thesis, King's College London (University of London), 2010. http://kclpure.kcl.ac.uk/portal/en/theses/contribution-of-p38-mitogen-activated-protein-kinase-isotypes-to-cardiac-physiology(9976a51e-2703-4ead-8746-a1bbc3a56326).html.
Full textNishimura, Masaki. "Activation of p38 kinase in the gerbil hippocampus showing ischemic tolerance." Kyoto University, 2005. http://hdl.handle.net/2433/144725.
Full text0048
新制・課程博士
博士(医学)
甲第11401号
医博第2824号
新制||医||888(附属図書館)
23044
UT51-2005-D151
京都大学大学院医学研究科脳統御医科学系専攻
(主査)教授 下遠野 邦忠, 教授 淀井 淳司, 教授 影山 龍一郎
学位規則第4条第1項該当
Fritz, Martina Désirée. "p38 MAP Kinase Inhibitoren : Synthese, Analytik und biologische Testung substituierter Isoxazole /." [S.l. : s.n.], 2004. http://www.gbv.de/dms/bs/toc/39191703X.pdf.
Full textLepage, Pierre 1962. "Activation of the mouse mdr3 gene in multidrug resistant derivatives of the lymphoid tumor P388." Thesis, McGill University, 1995. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=28822.
Full textKlameth, Nelli [Verfasser], and Martin A. [Akademischer Betreuer] Wahl. "Permeationsmechanismus und intrazelluläre Aufnahme von p38α-MAP-Kinase-Inhibitoren / Nelli Klameth ; Betreuer: Martin A. Wahl." Tübingen : Universitätsbibliothek Tübingen, 2016. http://d-nb.info/1197694722/34.
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