Dissertations / Theses on the topic 'Ba93'
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Kingham, Rachel. "The broad-scale impacts of livestock grazing on saltmarsh carbon stocks." Thesis, Bangor University, 2013. https://research.bangor.ac.uk/portal/en/theses/the-broadscale-impacts-of-livestock-grazing-on-saltmarsh-carbon-stocks(a81ba92d-ac40-49c4-ba93-982bffb077d9).html.
Full textDe, Marco Margot. "BAG3 role in cardiomyocytes physiopathology." Doctoral thesis, Universita degli studi di Salerno, 2013. http://hdl.handle.net/10556/896.
Full textThe anti-apoptotic protein BAG3 is expressed at high levels in skeletal and cardiac muscle in vivo. Our group recently focused its interest on BAG3 role in myocardiocyte proliferation, survival and response to stressful stimuli. We found that BAG3 is upregulated during the differentiation of cardiomyoblasts. Our results prompted us to verify whether bag3 silencing could affect the differentiation state of cardiocytes and we found that bag3 silencing resulted in highly reducing the levels of myogenin. Furthermore, we analyzed BAG3 expression and localization following cell exposure to oxidative stress. In particular, we found that epinephrine in vitro increases BAG3 expression in adult human cardiomyocytes. We evaluated whether BAG3 could be involved in the Tako-tsubo cardiomyopathy (or stress cardiomyopathy) pathogenesis that is characterized by left ventricular dysfunction, with symptoms that can mimic an acute coronary syndrome. The absence of significant cardiovascular risk factors in patients affected by stress cardiomyopathy suggested that it might be associated with a possible genetic etiology. Therefore, we sequenced bag3 gene to check for polymorphisms in 29 patients and 1043 healthy donors. Three polymorphism were highly represented among patients (R71Q, C151R, P407L). We also showed for the first time that BAG3 protein is released from stressed cardiomyocytes and is found in chronic heart failure (HF) patients’ sera. Since anti-BAG3 antibodies are also present in patients’ sera, we developed an ELISA test for their specific detection. In serum samples from chronic HF patients, we found significantly higher values of anti-BAG3 antibodies respect to samples from healthy donors. The presence of anti-BAG3 antibodies in chronic HF patients’ sera and the availability of an ELISA test for their detection can contribute a novel tool for diagnostic and prognostic evaluations. [edited by author]
X n.s.
D'Auria, Raffaella. "BAG3 extracellulare: target cellulari e molecolari." Doctoral thesis, Universita degli studi di Salerno, 2016. http://hdl.handle.net/10556/2355.
Full textBcl-2-associated athanogene 3 (BAG3) belongs to the family of co-chaperone proteins that interact with the heat shock protein 70 (Hsp70) and is involved in a number of cellular processes including proliferation and apoptosis. BAG3 contains the BAG domain which interacts with the ATPase domain of Hsp70. BAG3 is also characterized by the presence of a WW domain, two conserved Ile-Pro-Val (IPV) motifs and a proline-rich (PXXP) repeat that mediate the binding to partners different from Hsp70. These diverse and multiple interactions underlie the ability of BAG3 to modulate major biological processes such as development, cytoskeleton organization and autophagy. In our laboratory, BAG3 has been recently found in a soluble or membrane-associated form and it has been detected in the serum obtained from patients with pancreatic cancer or heart failure. Moreover, we found that BAG3 is able to bind the cell surface of macrophages and activate the production of inflammatory associated components, such as Nitric Oxide (NO) and Interleukin (IL) -6. To identify novel interacting partners of BAG3 an affinity chromatography on nickel-charged resin was performed, in J774A.1 cells, using recombinant BAG3 (rBAG3) followed by mass spectrometry analysis of the rBAG3-containing complexes. Among these, Interferon- Inducible TransMembrane (IFITM) -2 and Neuropilin (NRP) -1 were the only transmembrane proteins and therefore represented good candidates as receptors for BAG3. Our results show that NRP-1 and IFITM-2 are both essential for the binding of rBAG3 to the cell surface of macrophages and its activation for IL-6 release. We then investigated if BAG3 binding activates some of the signaling pathways known to be involved in macrophage activation. In particular we focused on the phosphatidylinositol 3-kinase (PI3K) and on the p38 pathway that are both involved in Cox-2, iNOS and IL-6 induction in macrophages. We demonstrated that BAG3 signaling is mediated by the receptor complex we identified, since IFITM-2 and/or NRP-1 silencing abrogates BAG3- induced phosphorylation of AKT and p38. We than focus our study on human monocytes, rBAG3 binds the cell surface and induces the release of many pro-inflammatory cytokines and chemokines. Furthermore, we have shown that rBAG3 can bind T lymphocytes cells surface after lipopolysaccharide (LPS) stimulus. All together these findings suggest a role for extracellular BAG3 in immune response. [edited by Author]
XIV n.s.
Falco, Antonia. "Ruolo della proteina BAG3 nel microambiente tumorale." Doctoral thesis, Universita degli studi di Salerno, 2012. http://hdl.handle.net/10556/293.
Full textRecenti studi hanno dimostrato che il microambiente tumorale subisce numerosi cambiamenti nel corso dello sviluppo del tumore e influenza l’evoluzione e la progressione del cancro. L'ambiente ipossico del tumore stimola l'angiogenesi che può direttamente promuovere la sopravvivenza delle cellule tumorali e la loro invasione. Anche l'infiltrato infiammatorio, associato a molti tumori solidi, è in grado di modulare il comportamento delle cellule tumorali, con effetti anti- e pro-tumorali. Un ruolo importante è svolto anche dai fibroblasti che circondano il tumore, i quali sono in grado di rilasciare fattori di crescita e citochine che stimolano l’ angiogenesi, la crescita del tumore e l'invasione. Tutti questi componenti sono potenziali bersagli per nuove strategie terapeutiche, e, infatti, diverse molecole che agiscono su tali target, sono attualmente utilizzate nelle sperimentazioni cliniche. Inoltre, dati recenti dimostrano che alcuni componenti del microambiente tumorale sono in grado di fornire importanti informazioni prognostiche e predittive. A tale scopo diventa sempre più evidente che, una caratterizzazione completa delle molecole e delle cellule coinvolte nel microambiente del tumore, è richiesta per una maggiore conoscenza della biologia del tumore. BAG3 è una proteina citoplasmatica che è stata recentemente caratterizzata per il suo ruolo centrale in diversi processi associati al tumore quali la sopravvivenza, la proliferazione, la migrazione e l'autofagia. Il ruolo di BAG3 nel microambiente associato al tumore non è stato caratterizzato finora. Pur non avendo un dominio transmembrana, i nostri studi hanno dimostrato che BAG3 può essere associata alla membrana plasmatica e rilasciata nel mezzo extracellulare di alcune cellule neoplastiche e in particolare cellule tumorali del pancreas. Abbiamo anche confermato la presenza di una forma extracellulare di BAG3 nel siero di pazienti affetti da adenocarcinoma pancreatico. Dopo il rilascio nello spazio extracellulare, BAG3 può legare la superficie di cellule adiacenti al tumore, e in particolare abbiamo cercato di stabilire se BAG3 può avere un effetto sui macrofagi che svolgono un ruolo importante nel microambiente infiammatoria associato al tumore. Abbiamo trovato che BAG3 è in grado di legare la superficie cellulare dei macrofagi e di indurre la produzione di componenti associati al processo infiammatorio. Abbiamo anche individuato un nuovo ruolo per BAG3 intracellulare nella regolazione della neo-angiogenesi. Infatti, abbiamo dimostrato che BAG3 è espressa nelle cellule endoteliali e che è in grado di regolare la proliferazione cellulare interagendo con ERK1/2 e la sua fosfatasi DUSP6. Come conseguenza, la riduzione di BAG3 determina una sostenuta fosforilazione di ERK1/2 e una ridotta crescita delle cellule endoteliali in vitro e in vivo. Questo, a sua volta induce una ridotta crescita del tumore in vivo in conseguenza alla ridotta angiogenesi. Complessivamente questi risultati permettono di individuare per la proteina BAG3 un ruolo nuovo nella regolazione dello sviluppo del tumore. [a cura dell'autore]
IX n.s.
Myers, Valerie. "The Role of BAG3 in the Failing Heart." Diss., Temple University Libraries, 2018. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/490584.
Full textPh.D.
Heart disease has been the leading cause of death in the United States for more than 90 years. The leading cause of death in individuals aged 65 and older has remained diseases of the heart from 1950 to the current time. According to the CDC, once diagnosed with heart disease, individuals have an approximately 50% chance of dying within 5 years, regardless of race. Mortality related to heart disease increased dramatically from the start of the 1900s to 1921, but subsequently experienced a steady decline from the mid-1960’s to 2000. However, when the decrease in heart disease is examined at the level of race it is clear that the decrease is not equally shared. While the leading cause of death among both Caucasian American men and women and African American men and women remains heart disease, the decrease in incidence of coronary heart disease among African American men was only half of the decrease in incidence among Caucasian American men. Genetic variants in BAG3 (Bcl-2 associated athanogene 3), a highly evolutionarily conserved gene that has recently emerged as a major dilated cardiomyopathy locus, are prevalent in isolated populations. This led us to hypothesize that variants in BAG3 might contribute to the increased prevalence of IDC in individuals of African ancestry. Expressed predominantly in the heart, the skeletal muscle and in many cancers, BAG3 has pleotropic effects in the heart. It inhibits apoptosis by binding to Bcl-2, facilitates protein quality control by binding to both large and small heat shock proteins, mediates adrenergic responsiveness by coupling the β-adrenergic receptor and the L-type Ca2+ channel, and maintains the integrity of the sarcomere by anchoring actin filaments to the Z disc. However, a paucity of subjects of African ancestry have been included in cohorts of probands with familial dilated cardiomyopathy whose exomes or genomes have been sequenced. Based on our previous observations and reports from other groups we postulated: 1) that mice with haplo-insufficiency of BAG3 will re-capitulate disease seen in humans and serve as a model for studying the pathogenesis of BAG3. 2) The prevalence or identification of specific BAG3 variants will differ by race and/or ethnicity. 3) SNVs of BAG3 may contribute to disease progression and thereby be pathogenic. Our study points out that we cannot understand population-based differences without enhancing the diversity of populations included in genomic studies. Similarly, in the era of big data, efforts must be undertaken to assess the genetic profile of both probands and their family members as without the ability to measure segregation, penetrance and plasticity we can only ascribe associations to functional genetic variants.
Temple University--Theses
Engelmann, Ines. "Änderung der Stoffwechselaktivität von BaF3-Zellen durch die Expression von BCR/ABL." Doctoral thesis, Universitätsbibliothek Leipzig, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-163535.
Full textKorniat, Agathe. "Etude fonctionnelle des variants moléculaires du gène BAG3 associés à la cardiomyopathie dilatée humaine." Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066716.
Full textThe BAG3 gene was identified as a novel gene responsible for dilated cardiomyopathy (DCM), a major cause of heart failure (HF). The BAG3 protein is a co-chaperone that participates in the control of protein homeostasis via its role in autophagy, protecting cells against the proteotoxicity induced by degraded or misfolded proteins. The hypothesis that inactivation of the autophagic pathway controlled by BAG3 would induce cardiomyocyte proteotoxicity behind the CMD appears particularly attractive and is the central hypothesis of this work. Our results indicate that BAG3 mutations abolish the interaction with the chaperone HSP70, a central actor of the protein quality control. We observed cytotoxicity of BAG3 mutants, an impaired HSP70-dependent chaperone function and absence of autophagic response under stress conditions (starvation, heat shock, expression of a pro-aggregating protein). In vivo (zebrafish model) the extinction of BAG3 expression or mutants overexpression lead to the occurrence of a heart failure phenotype (pericardial edema) in injected embryos. Through genomic edition, we also develop a model of iPS-derived cardiomyocytes carrying or not the mutation in order to further explore the contractile function of these cells. Our results confirm the role of BAG3 in DCM and indicate that the alteration of the proteostasis function is the cause of the disease. This new pathophysiological pathway in DCM may prove to be more generally, a central line in the IC
Manchen, Steven T. "Characterization and subcellular localization of the human BAT3 protein." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp05/MQ62248.pdf.
Full textIsaksen, Katja. "Consumer culture, branding and British adolescents : a vicious cycle? : a comparison between high and low-income adolescents." Thesis, University of Manchester, 2010. https://www.research.manchester.ac.uk/portal/en/theses/consumer-culture-branding-and-british-adolescents-a-vicious-cycle-a-comparison-between-high-and-lowincome-adolescents(94a6b8e2-c339-447b-ba93-110b4dc22755).html.
Full textPeña, Oyarzún Daniel. "Rol de BAG3 en la regulación del metabolismo muscular esquelético." Tesis, Universidad de Chile, 2014. http://repositorio.uchile.cl/handle/2250/134613.
Full textAutor no autoriza el acceso a texto completo de su documento hasta diciembre de 2015
La proteína co-chaperona Bag3 es un factor clave en el control de la autofagia selectiva, un proceso de degradación de proteínas y organelos activado en respuesta a distintos estresores, en tejidos altamente diferenciados, como el músculo esquelético. Este último tejido transforma la energía química del ATP en energía mecánica para la contracción, por lo que el control del metabolismo de la glucosa resulta fundamental para mantener su función fisiológica. En este sentido, insulina, a través de sus efectores intracelulares Akt y mTORC1, promueve el ingreso y metabolismo de la glucosa. No obstante, en condiciones de estrés nutricional la proteína AMPK activa la autofagia para aumentar el metabolismo celular por degradación de diversas macromoléculas. Prueba de esta relación funcional entre metabolismo y autofagia es que la inhibición de la autofagia lleva a resistencia a la insulina en células musculares esqueléticas. Por otro lado, existe evidencia que los ratones knock-out para Bag3 presentan una disminución en los niveles de glucosa e insulina circulantes, y mueren a las 3 semanas de nacimiento con deterioro muscular progresivo. Sin embargo, hasta hoy se desconoce si Bag3 regula el metabolismo energético de la célula, y si las vías que controlan ese metabolismo se relacionan con la autofagia. En vista de estos antecedentes, se investigó si Bag3 altera la señalización de la vía Akt-AMPK-mTORC1, produciendo efectos metabólicos y de autofagia en miotubos L6 (línea celular: músculo esquelético de rata). A través de ensayos de captura de 3H-2-desoxiglucosa, consumo de oxígeno y detección densitométrica de GLUT4-myc en superficie, se determinó que las células con niveles reducidos de Bag3 (RNA interferente) y sin insulina en el sistema, incorporaron mayor cantidad de glucosa por un incremento de transportadores Glut-4 en la membrana celular junto con una mayor capacidad oxidativa mitocondrial. Lo anterior es debido a un aumento de la activación basal de Akt, evidenciado por Western blot contra Fosfo-Ser-473. Además, estas células presentaron una menor capacidad de activar la autofagia debido a un procesamiento disminuido de LC3, además de una menor activación de AMPK (Fosfo-Thr-172) y una sobre-activación de mTORC1 (Fosfo-Ser-2448). Finalmente, en presencia de insulina (100 nM, 20 min), las células con niveles reducidos de Bag3 presentaron una incorporación deficiente de glucosa para la cantidad de transportador Glut-4 exportado a la membrana, y una menor capacidad oxidativa mitocondrial. En estas condiciones, Akt se activó de forma normal ante insulina, observándose sin embargo que AMPK y mTORC1 se activó e inactivó, respectivamente; comportamiento inverso respecto a lo normal. Con estos datos, se propone a Bag3 como un novedoso regulador del metabolismo y la autofagia muscular esquelética
The co-chaperone protein Bag3 is a key factor for the control of selective autophagy, a degradation process of proteins and organelles activated in response to stress, in highly differentiated tissues, as the skeletal muscle. The role of the latter is to transform the chemical energy from ATP into mechanical energy for contraction, thus the metabolism control of glucose is important to keep its biological function. In that way, the hormone insulin, by its intracellular effectors Akt and mTORC1, promotes the uptake and metabolism of glucose. However, in nutritional stress conditions the AMPK protein activate autophagy in order to increase cellular metabolism by macromolecular degradation. Proof of this functional relationship between metabolism and autophagy is that autophagy abrogation leads to insulin resistance in muscle cells. On the other hand, there is evidence that shows that Bag3 Knock-out mice present diminished glucose and insulin in blood, and die after 3 weeks from birth with progressive muscle wasting. However, it is not known yet whether Bag3 regulates energy metabolism in the cell, nor whether the pathways that control that metabolism are related with Bag3 mediated autophagy. With this in mind, we decided to determine if Bag3 was able to alter the Akt-AMPK-mTORC1 signaling pathway, leading to metabolic and autophagy effects, in L6 myotubes (cell line: skeletal muscle from rat). By 3H-2-desoxyglucose uptake, oxygen consumption and GLUT4-myc surface detection assays, we were able to determine that cells with reduced levels of Bag3 (interference RNA), and without insulin in the system, had increased glucose uptake because of an augmented Glut-4 translocation to the cell membrane, along with an enhanced mitochondrial oxidative capacity. This is explained by an increased Akt basal activation, evidenced by Phospho-Ser-473 western blot. Furthermore, these cells showed a diminished capacity to produce autophagy, because of a decreased LC3 processing, along with a diminished activation of AMPK (Phospho-Thr-172) and an over activation of mTORC1 (Phospho-Ser-2448). Finally, in the presence of insulin (100 nM, 20 minutes), cells with diminished levels of Bag3 showed a deficient glucose uptake for the amount of Glut-4 transporter exported to cell membrane, and a decreased mitochondrial oxidative capacity. Under these conditions, Akt protein increased its activation, as normal, but AMPK was activated and mTORC1 was inactivated, an inverted behavior with respect to normal metabolism. With these data, we propose Bag3 as a novel regulator of metabolism and autophagy in muscle
Schröter, Thomas. "Charakterisierung der ba3 Chinoloxidase aus Paracoccus denitrificans." [S.l. : s.n.], 2000. http://deposit.ddb.de/cgi-bin/dokserv?idn=961246944.
Full textSebti, Salwa. "Rôle de la protéine BAT3 dans la signalisation cellulaire de l'autophagie." Thesis, Montpellier 1, 2013. http://www.theses.fr/2013MON1T028.
Full textAutophagy, literally meaning self-eating, is a highly evolutionary conserved process in eukaryotes in which parts of the cytoplasm (organelles, macromolecules) are degraded by lysosomes. Basal autophagy is a quality control mechanism allowing the renewal of the cytoplasm but autophagy is also induced by cellular stress (starvation, hypoxia…) to improve cell survival. Autophagy has been implicated in several physiopathologies such as cancer or neurodegenerative diseases. Deregulations of autophagy may profoundly affect homeostasis.The purpose of my thesis is to explore the role of the nucleo-cytoplasmic shuttling protein BAT3 in autophagy and the mechanism of BAT3-dependent autophagy.Also known as BAG6 or Scythe, this 150 kDa protein is composed of various domain (UBL, Prolin-Rich, NLS, BAG) by which BAT3 interacts with multiple partners. The major of role BAT3 seems to be the protein quality control but BAT3 is also implicated in immunity and apoptosis. Our work demonstrates that the protein BAT3 is essential for basal and starvation-induced autophagy. We show that BAT3 regulation of autophagy is mediated by the modulation of p300 acetyltransferase intracellular localization and acetylation of two subtrates: p53 and the autophagy-related protein ATG7. Indeed, Bat3 allows: (i) the limitation of p300 into cytosol resulting in (ii) the maintenance of a low level of ATG7 acetylation and (iii) the increase of the starvation-induced p53 autophagy leading to the induction of autophagy
Wördehoff, Judith Friederike [Verfasser]. "Regulation des Cochaperons BAG3 durch Phosphorylierung und Dephosphorylierung / Judith Friederike Wördehoff." Bonn : Universitäts- und Landesbibliothek Bonn, 2020. http://d-nb.info/1225793106/34.
Full textRodríguez, Villarroel Andrea Elizabeth. "Estudio de los mecanismos de regulación de la autofagia por BAG3." Tesis, Universidad de Chile, 2015. http://repositorio.uchile.cl/handle/2250/136770.
Full textAutor no autoriza el acceso a texto completo de su documento
La macroautofagia (autofagia) es una vía de reciclaje caracterizada por la formación de vesículas de doble membrana denominadas autofagosomas que secuestran estructuras citoplasmáticas marcadas para su degradación. La formación del autofagosoma requiere la actividad de proteínas relacionadas con la autofagia (Atg) que median algunas de las cuatro etapas principales de la autofagia: iniciación, nucleación, expansión y cierre. La proteína MAP1LC3B (referida sólo como LC3) es una de las Atg más importantes ya que ayuda a elongar la membrana y reclutar al cargo. Su forma lipidada (LC3-II) se encuentra en ambas superficies del autofagosoma (externa e interna) donde se degrada con su cargo cuando el autofagosoma se fusiona con el lisosoma. La autofagia se regula principalmente por modificaciones post-traduccionales y modificaciones lipídicas de las proteínas Atg. Además, en algunos escenarios, la inducción de la autofagia se acompaña de aumentos en los niveles de mRNA de ciertos genes asociados a la autofagia, como LC3, ATG5 o ATG12. Sin embargo, prácticamente se desconocen los mecanismos que controlan la traducción de las proteínas Atg. Estudios recientes con la cochaperona Bag3 han mostrado controlar la degradación selectiva de proteínas mal plegadas a través de autofagia, incluyendo huntingtina con expansiones de poli-Q y SOD1 mutante. El mecanismo involucra la asociación de Bag3 a dineína y microtúbulos para el transporte de proteínas mal plegadas a los agresomas, facilitando su eliminación por la autofagia. Además del papel en el plegamiento y degradación de proteínas, recientemente se ha descrito que la chaperona Hsp70 regula la traducción de proteínas. Los últimos trabajos muestran que Bag3 es una proteína que induce la lipidación LC3 pero no hay antecedentes sobre el mecanismo utilizado. En esta tesis se estudió cómo Bag3 controla la autofagia en células HeLa. Para este fin Bag3 se silenció con un siRNA ó shRNA, o se expresó con plasmidios. Los niveles de mRNA, proteínas y estado de fosforilación de varias proteínas Atg, particularmente de LC3I y LC3II, mTOR y AMPK. Además, se determinó si Bag3 es necesaria para la inducción de la autofagia en condiciones de estrés como la privación de nutrientes e inhibición del proteasoma. Los resultados mostraron que Bag3 mantiene los niveles basales de la proteína LC3 en células HeLa, controlando la traducción de su mRNA. El efecto de Bag3 es aparentemente específico para LC3 dado que otras proteínas Atg no fueron afectadas. De hecho, la conversión de LC3I a LC3II por inductores autofagia, como la privación de nutrientes y la inhibición del proteosoma, no se observó afectada. Se concluye que Bag3 regula niveles proteicos totales de LC3, manteniendo su traducción
Macroautophagy (autophagy) is a recycling pathway characterized by the formation of double-membrane vesicles called autophagosomes, which sequester cytoplasmic structures targeted for destruction. Autophagosome formation requires the activity of autophagy-related proteins (Atg), which are shown to participate in the four major steps: initiation, nucleation, expansion and closure. MAP1LC3B (referred only as LC3) is most important Atg protein, aiding to elongate the membrane and recruit the cargo. The lipidated form of LC3 (LC3-II) lies on both surfaces of autophagosome (external and internal) where it degrades with its cargo when the autophagosome fuses with the lysosome. Autophagy is mainly regulated by post-translational modifications and lipid modifications of Atg proteins. Moreover, in some scenarios, the induction of autophagy is accompanied by an increase in the mRNA levels of certain genes associated to autophagy, such as LC3, ATG5 or ATG12. However, less work has done on the study of mechanisms controlling translation of the Atg proteins. In recent studies, Bag3 has shown to control the selective degradation of misfolded proteins by autophagy, including polyQ-expanded huntingtin and mutant SOD1. The mechanism involves Bag3 association to dynein and microtubules to transport misfolded proteins to the aggresomes and facilitates their clearance by autophagy. Besides the role in folding and degradation of proteins, recently has shown a role of the Hsp70 chaperone in the regulation of the translation of proteins. The last reports show that Bag3 is a protein that induces LC3 lipidation but little is known about the mechanisms used. In the present work, we study how Bag3 controls the autophagy pathway in HeLa cells. Bag3 was knockdown with siRNA or shRNA, or expressed with plasmids. mRNA levels, protein levels and phosphorylation status of several Atg, particularly of LC3I and LC3II, mTOR and AMPK were evaluated. In addition, it was determined whether Bag3 is required for the induction of autophagy in stress conditions such as nutrient deprivation and inhibition of the proteasome. Our results showed that Bag3 maintains the basal protein levels of LC3 in HeLa cells, controlling the translation of its mRNA. This effect was apparently specific for LC3 because the levels of other Atg proteins remained unchanged. The LC3I conversion to LC3II did not alter by autophagy inductors such as nutrient deprivation or proteasome inhibition. We concluded that Bag3 maintains the basal protein levels of LC3, controlling the translation of its mRNA
Conicyt Fondecyt Fondap Proyecto Anillo ACT 1111
Guerriero, Luana. "Studio del ruolo della proteina anti-apoptotica BAG3 nel melanoma umano." Doctoral thesis, Universita degli studi di Salerno, 2016. http://hdl.handle.net/10556/2350.
Full textBAG3 protein, a member of BAG family of co-chaperones, has a pro-survival role in several tumor types. BAG3 anti-apoptotic properties rely on its characteristic to bind several intracellular partners, thereby modulating crucial events such as apoptosis, differentiation, cell motility and autophagy. In human melanomas, BAG3 positivity is correlated with the aggressiveness of the tumor cells and can sustain IKK-γ levels, allowing a sustained activation of NF-B. Furthermore, BAG3 is able to modulate BRAFV600E levels and activity in thyroid carcinomas. BRAFV600E mutation is the most frequent detected in malignant melanomas and is targeted by Vemurafenib, a molecule used for the treatment of advanced melanoma. However a subset of patients resulted not sensitive or acquired resistance to this molecule. Here we confirmed that BAG3 expression is significantly enhanced in metastasis in respect to primary tumors, than we demonstrated that BAG3 protein expression was significantly enhanced in metastasis of patients carring BRAFV600E mutation. Furthermore we found a significant correlation between BAG3 positivity and patients’ overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS) from surgery in patients with melanoma metastatic lymph nodes. Moreover here we show that BAG3 down-modulation interferes with BRAF levels in melanoma cells and sensitizes them to Vemurafenib treatment. Furthermore, in an in vitro model of acquired resistance to Vemurafenib, we demonstrated that the down-modulation of BAG3 protein can resensitize this cells to BRAFV600E specific inhibition interfering with BRAF pathway, causing reduction of ERK and its targets phosphorylation. Further studies will be focused in demonstrating our hypothesis that the molecular interactions between BAG3 and mutated BRAF can represent a target for novel multi-drugs treatment design and that BAG3 expression could contribute to prognosis and patient stratification for specific therapeutic approaches. [edited by Author]
XIV n.s.
Korniat, Agathe. "Étude fonctionnelle des variants moléculaires du gène BAG3 associés à la cardiomyopathie dilatée humaine." Electronic Thesis or Diss., Paris 6, 2015. http://www.theses.fr/2015PA066716.
Full textThe BAG3 gene was identified as a novel gene responsible for dilated cardiomyopathy (DCM), a major cause of heart failure (HF). The BAG3 protein is a co-chaperone that participates in the control of protein homeostasis via its role in autophagy, protecting cells against the proteotoxicity induced by degraded or misfolded proteins. The hypothesis that inactivation of the autophagic pathway controlled by BAG3 would induce cardiomyocyte proteotoxicity behind the CMD appears particularly attractive and is the central hypothesis of this work. Our results indicate that BAG3 mutations abolish the interaction with the chaperone HSP70, a central actor of the protein quality control. We observed cytotoxicity of BAG3 mutants, an impaired HSP70-dependent chaperone function and absence of autophagic response under stress conditions (starvation, heat shock, expression of a pro-aggregating protein). In vivo (zebrafish model) the extinction of BAG3 expression or mutants overexpression lead to the occurrence of a heart failure phenotype (pericardial edema) in injected embryos. Through genomic edition, we also develop a model of iPS-derived cardiomyocytes carrying or not the mutation in order to further explore the contractile function of these cells. Our results confirm the role of BAG3 in DCM and indicate that the alteration of the proteostasis function is the cause of the disease. This new pathophysiological pathway in DCM may prove to be more generally, a central line in the IC
Zeidler, Claudia [Verfasser]. "Functional Characterization of Interaction Partners of the Co-Chaperone BAG3 / Claudia Zeidler." Bonn : Universitäts- und Landesbibliothek Bonn, 2018. http://d-nb.info/116059452X/34.
Full textSchwarz, Mario [Verfasser]. "Untersuchung autophagischer Prozesse mit Fokus auf BAG3 und seine Interaktoren. / Mario Schwarz." Mainz : Universitätsbibliothek der Johannes Gutenberg-Universität Mainz, 2021. http://d-nb.info/1225796059/34.
Full textEngelmann, Ines [Verfasser], Thoralf [Akademischer Betreuer] Lange, and Michael [Akademischer Betreuer] Cross. "Änderung der Stoffwechselaktivität von BaF3-Zellen durch die Expression von BCR/ABL : Änderung der Stoffwechselaktivität von BaF3-Zellen durch die Expression von BCR/ABL / Ines Engelmann ; Thoralf Lange, Michael Cross." Leipzig : Universitätsbibliothek Leipzig, 2015. http://d-nb.info/1239564937/34.
Full textRusso, Alessandra. "Design, synthesis and biological activity of new target selective antitumoral agents." Doctoral thesis, Universita degli studi di Salerno, 2018. http://hdl.handle.net/10556/3037.
Full textCancer development is a complex pathological process that exploits a variety of biological actors. The identification of new molecular entities able to interfere with new biological targets, involved in tumorigenesis, is strongly needed, both for the development of new promising drug candidates, and, as chemical probes useful to further investigate less understood biological aspects. Two main targets, involved at different levels, in cancer development, have been thoroughly investigated: Macrodomain proteins, MacroD1 and MacroD2, and the Bcl-2 associated athanogene 3, BAG3 protein... [edited by Author]
XXX ciclo
Lanoue, Vanessa. "Rôle du récepteur BAI3 dans le développement neuronal - Études in vitro et in vivo -." Phd thesis, Université Pierre et Marie Curie - Paris VI, 2012. http://tel.archives-ouvertes.fr/tel-00865692.
Full textKnezevic, Tijana. "TRANSLATIONAL APPROACH TO INVESTIGATE INVOLVEMENT OF BAG3 IN PROTEIN QUALITY CONTROL AND HEART FAILURE." Diss., Temple University Libraries, 2016. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/374885.
Full textPh.D.
Heart failure continues to be a global problem, even with all the drugs currently available, leading to a need of new therapeutics to decrease incidence of heart failure. Heart failure is the inability of the heart muscle to pump sufficient blood and oxygen to the rest of the body. One of the causes of heart failure is cardiomyopathy, where cardiac muscle becomes larger and weaker. Genetic mutations in genes encoding sarcomeric, structural and cytoskeletal proteins were found in families that developed cardiomyopathy. Our laboratory has indentified a family with heart failure in whom a novel mutation in the BCL2-associated athanogene 3 (BAG3) has been characterized. Among other cardiomyopathy-causing BAG3 mutations reported in various laboratories. Several BAG3 mutations in humans are known to cause familial dilated cardiomyopathy, myofibrilar myopathy, and giant axonal neuropathy. BAG3 is a stress induced co-chaperone protein that interacts with several heat shock proteins and acts as an important regulator of protein quality control. Expression of BAG3 is high in cardiac, skeletal and smooth muscle. BAG3 is localized at the z-disk of cardiomyocytes and was shown to be essential in keeping a normal assembly of z-disk proteins during mechanical stretch. Interaction of BAG3 with actin capping protein CapZbeta1 prevents degradation of CapZbeta1 via proteasome system and maintains the integrity of the z-disk. BAG3 was shown to promote clearance of misfolded proteins, such as filamin C, via autophagy. Not only that BAG3 is able to promote clearance of dysfunctional filamin C, but it was found to enhance synthesis of the new filamin. BAG3 deficient mice develop fulminant myopathy and cardiomyopathy with disorganization of z-disk and die after one month of age. Not only that BAG3 is involved in myofibrilar stability in the cardiomyocytes and that patients with BAG3 mutations develop cardiomyopathy, but our lab showed that patients with heart failure have decrease levels of BAG3. Since heart failure patients have decreased levels of BAG3, the therapy where BAG3 levels are restored to normal levels may improve heart function. Here, I show that in mouse model of heart failure after MI left ventricle function is restored after administration of AAV9 BAG3. BAG3 overexpression in mouse heart helped the stability of z-disk proteins after mechanical stress and myocardial infarction. Overexpressed BAG3 localizes to z-disk and is also able to increase autophagy in cardiomyocytes and help with clearance of misfolded proteins. Taken together, this study shows that BAG3 is a valid and promising new therapeutic target for heart failure patients. BAG3 overexpression is able to induce autophagy and help the heart cope better with stress. Also, AAV9 vector is robustly expressed in the heart after systemic administration, and is a promising vector for gene delivery in the patient heart.
Temple University--Theses
Iorio, Vittoria. "Determinazione del ruolo della proteina BAG3 nelle isole del Langerhans e suo coinvolgimento nel meccanismo di secrezione dell’insulina." Doctoral thesis, Universita degli studi di Salerno, 2015. http://hdl.handle.net/10556/2041.
Full textDiabetes is a metabolic alteration due to a decrease in activity of insulin. In particular, it may be a consequence of a reduced availability of this hormone, of an impediment to its normal action, or of a combination of these two factors. The secretion of insulin is a specialized activity of t β cells of the Langerhans islets that are functional endocrine pancreatic part. Diabetes is a widespread disease, particularly in so-called affluent countries, where some risk factors promotes the onset. Actually, it should be considered a syndrome more complex than the simple hyperglycemia. In fact, it is associated to lipid metabolism abnormalities, and increased blood pressure, that, together with abdominal obesity and alterations in glucose homeostasis constitute the so called 'metabolic syndrome': a multifactorial disease that increases the risk of cardiovascular disease. Given to the wide prevalence of this disease, it is therefore necessary a deeper understanding of the normal physiology of β cells and a complete characterization of the molecules involved in the mechanism of insulin secretion. Recently, there has been much progress in this direction, but much remains to be clarified. BAG3 is a protein involved in some of the most important biological processes, such as apoptosis, autophagy, adhesion, migration, and cell invasion. The strong positivity of BAG3 protein in Langerhans islets, recently found in our laboratory, has prompted us to analyze the role of this protein in the β cells physiological functions. To this end, we analyzed BAG3 expression and subcellular localization in the murine insulinoma cell line β TC 6. BAG3 has an apparent mass of 74kDa and is localized in the cytoplasm, here has been shown the presence of a 60 kDa BAG3 form in the insulin- containing granules. The presence in this fraction can be explained by the fact that BAG3 appears to be associated with proteins constitutely expressed on the granules membranes involved in their exocytosis. Indeed, in this work, has been shown the physical interaction of BAG3 protein with t - SNARE SNAP -25 / Syntaxin, which mediate the fusion and exocytosis of insulin vesicles to the plasma membrane. In particular, BAG3 appears to regulate the assembly of the complex allowing a regulated secretion of insulin. In addition, we have shown that BAG3 interacts with the focal adhesion complex FAK / Paxilllin, involved in glucose induced F – actin remodeling. The interaction with FAK, induced by high glucose concentrations, appears to be essential for the phosphorylation of BAG3 by such kinases. BAG3 is also able to sustain ERK phosphorylation, contributing to the destruction of the actin cytoskeleton and increased secretion of insulin. All together these findings disclose a role for BAG3 in regulating insulin release by islet β- cell. [edited by author]
XII n.s.
Piedallu, Océane. "Physiopathologie d'un modèle murin knock-in d'une mutation du gène BAG3 responsable d'insuffisance cardiaque humaine." Electronic Thesis or Diss., Sorbonne université, 2024. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2024SORUL079.pdf.
Full textWe have successfully generated a new mouse model recapitulating dilated cardiomyopathy phenotype, including gender-dependant severity observed in humans, without the limitations associated with the previous similar model. This full knock-in model, expressing the hypomorphic V473M mutation of the BAG domain in Bag3, orthologous to the V468M mutation causing DCM in humans, enabled us to study the pathomechanisms involved both in the onset and later stage of the disease. The mutant mice were deficient in basal macroautophagy yet showed activation upon starvation-induced stimulation, indicating an alteration of specific rather than bulk macroautophagy. Co-expressing a proteotoxic pro-aggregative mutant desmin in Bag3-V473M mice unexpectedly improved cardiac function and increased desmin ubiquitinylation rather than exacerbate DCM features. This suggests that normal Bag3 function may worsen mutant-desmin associated proteotoxicity through aggrephagic pathway overload, while HSP70-interacting deficient V473M mutant may be incompetent in desmin aggregates cargo processing. Proteomic and transcriptomic analyses confirmed proteostasis dysregulation in mutant mice but also witness an early metabolic alteration consistent with a cardiac shift in energy supply from fatty-acids to glucose as an early event in the onset of the disease, supported by in vivo and cardiac lipidomic analyses. To conclude, our results shows that Bag3 BAG domain mutation impaired specific macroautophagy resulting in early cardiac metabolic dysregulation
Séguin, Samuel. "Le chaperon HSPB8 coopère avec BAG3 pour stimuler la dégradation des protéines à polyglutamine par macroautophagie." Thesis, Université Laval, 2008. http://www.theses.ulaval.ca/2008/25531/25531.pdf.
Full textWegehaupt, Oliver Philipp [Verfasser], and Michael [Akademischer Betreuer] Köttgen. "BAG2, BAT3, DNAJB11, GNB2L1 und SERPINH1 interagieren in einem Netzwerk mit dem Polycystin-1-TRPP2-Signalmodul." Freiburg : Universität, 2016. http://d-nb.info/1122647816/34.
Full textYu, Yanhua. "Functional characterization of AvrBs3/PthA effectors in Xanthomonas oryzae pv. oryzae strain BAI3 from West-Africa." Thesis, Montpellier 2, 2010. http://www.theses.fr/2010MON20231.
Full textXanthomonas oryzae pv. oryzae (Xoo) is the causal agent of Bacterial Leaf Blight (BLB) on rice, a serious disease causing important yield losses in the main rice growing regions including Africa. The virulence of Asian Xoo strains mainly depends on the type III effectors of avrBs3/pthA gene family, namely TAL (for Transcription Activator Like) effectors. In depth studies on the function of TAL effectors revealed that the virulence and/or the avirulence activities conferred by these effectors requires the binding and the induction of the corresponding S and/or R genes. African Xoo strains was shown to harbor 8 TAL effectors in their genomes. However, the contribution of these TAL effectors to Xoo virulence is still unknown. This work reports on the identification and characterization of TAL effectors in the African Xoo strain BAI3R. A random mutagenesis based on homologous recombination in the genes encoding TAL effector was conducted in Xoo str ain BAI3R and led to the identification of talC. TalC harbors 21.5 repeats in its central domain and is phylogenetically more related to TAL effectors of Xanthomonas oryzae pv. oryzicola (Xoc). The BAI3RΔtalC mutant is seriously impaired in its virulence on susceptible rice varieties. Interestingly, bacteria are still able to grow at wild-type levels in the apex of the leaf, suggesting a requirement of talc for vascular colonization. Potential direct host targets were identified by conducting a transcriptomic analysis of rice leaves challenged with Xoo strain BAI3R vs. BAI3RΔtalC. Among the identified targets, the rice gene Os11N3 was found to be highly induced upon infection by the wild type strain but not the mutant one. A DNA target box for TalC was located in the Os11N3 upstream region and proved to be functional using GUS assays. We also show that the Os11N3 341-bp upstream region is transcriptionnally activated by TalC. Our results demonstrated for the first time that TAL effectors play an important role in the virulence of Xoo strain BAI3R. Our work will contribute to better improve rice for resistance to bacterial leaf blight
Elders, Christopher Frank. "Caledonian tectonics from stratigraphy and isotope geochemistry of lower palaeozoic successions." Thesis, University of Oxford, 1987. http://ora.ox.ac.uk/objects/uuid:bf48a950-7ffb-4b58-bae3-915a2f7b5a94.
Full textDylan, Huw. "The Joint Intelligence Bureau : economic, topographic, and scientific intelligence for Britain's Cold War, 1946-1964." Thesis, Aberystwyth University, 2010. http://hdl.handle.net/2160/6338ec52-6154-47ca-ba92-c6bf092281bf.
Full textOliver, Jacob B. "Birthing Attila." Thesis, Aberystwyth University, 2015. http://hdl.handle.net/2160/3a37bc8b-6a4a-470d-ba90-452dfb823617.
Full textBeattie, Melissa. "Travelling Torchwood(s) : national and transnational identities, glocalisation and the pseudo-reflexive audience." Thesis, Aberystwyth University, 2017. http://hdl.handle.net/2160/d019a8ca-5018-4cb3-ba9f-47304fa78910.
Full textModh, Sandra Violeta. "Lamaholot of East Flores : a study of a boundary community." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:b7693f46-3a18-4b1a-ba96-0f17e91f0282.
Full textRoberts, Thomas C. "Duchenne muscular dystrophy : RNA-based therapeutics and microRNA biology." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:f53ea1f3-92db-4f90-ba95-01f2a56eae8f.
Full textAhmed, Farrah. "Religious autonomy and the personal law system." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:e8d532c3-be53-4823-ba9d-bb78a9aaefcc.
Full textBozhilov, Yavor. "Analysis of a gain-of-function mutation that produces a new transcriptional unit in the α-globin locus." Thesis, University of Oxford, 2017. http://ora.ox.ac.uk/objects/uuid:c6979237-b318-47a6-ba03-8aab85c33d63.
Full textRazak, Huzaifah Haritsah Abdul. "Wetting behaviour of colloid-polymer mixtures in confinement." Thesis, University of Oxford, 2017. https://ora.ox.ac.uk/objects/uuid:e75a8463-fe02-46f3-ba95-7d7b40c955cb.
Full textScaber, Jakub. "The pathophysiological role of TDP-43 in amyotrophic lateral sclerosis due to C9orf72 mutations." Thesis, University of Oxford, 2017. https://ora.ox.ac.uk/objects/uuid:c5dd8dcf-c3e0-4ff7-ba9d-bfd3cb9914e8.
Full textMan, James K. C. "Characterisation of a novel animal model for obsessive-compulsive disorder." Thesis, University of Bristol, 2005. http://hdl.handle.net/1983/6cec00ce-f3c1-4d07-ba98-54c137b7524a.
Full textStamatopoulou, Despina. "Aesthetic experience and self-esteem in adolescents." Thesis, University of Bristol, 1993. http://hdl.handle.net/1983/f2b2f32f-0c56-4a7b-baa3-c593aebf2292.
Full textEllenrieder, Thomas Jochen. "Investigation of the dynamic wake of a model rotor." Thesis, University of Bristol, 1995. http://hdl.handle.net/1983/13c5bb18-5952-41ae-ba03-08d8d2040d12.
Full textDodds, Klaus-John. "Critical geopolitics and the writing of foreign policy." Thesis, University of Bristol, 1993. http://hdl.handle.net/1983/54c2c69d-717d-4def-ba92-eff80f4d13c6.
Full textPatsios, Demetrios. "Modelling the dynamic relationship between formal and informal long-term care between 1980 and 1995 in Britain : a multilevel approach." Thesis, University of Bristol, 2001. http://hdl.handle.net/1983/2897487e-5e0d-41e0-ba03-ad3f5d9a8641.
Full textHayward, Robert C. "The significance of withdrawal in a multidisciplinary profile of tobacco dependence." Thesis, University of Bristol, 2003. http://hdl.handle.net/1983/fecadd04-2154-439a-baa3-7ba3fa983ecc.
Full textDobnik, Simon. "Teaching mobile robots to use spatial words." Thesis, University of Oxford, 2009. http://ora.ox.ac.uk/objects/uuid:d3e8d606-212b-4a8e-ba9b-9c59cfd3f485.
Full textThan, Manuel E. "Röntgenstrukturanalyse der Ba3-Cytochrom-c-Oxidase aus Thermus thermophilus und ihres Substrates Cytochrom-c552." [S.l. : s.n.], 2000. http://deposit.ddb.de/cgi-bin/dokserv?idn=959982051.
Full textFelzen, Vanessa [Verfasser]. "Regulation and function of autophagy in stress resistance and under pathophysiological conditions involves the co-chaperone BAG3 / Vanessa Felzen." Mainz : Universitätsbibliothek Mainz, 2016. http://d-nb.info/110992111X/34.
Full textDavies, A. C. L. "Accountability : a public law analysis of National Health Service contracts." Thesis, University of Oxford, 1999. https://ora.ox.ac.uk/objects/uuid:7fa277f4-ba95-46e6-bd82-81ab2236acd5.
Full textKatsaroumpas, Ioannis. "Collective labour law in times of economic crisis : theoretical and comparative perspectives." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:1f8bb178-12db-45e6-ba90-0fdcac45429b.
Full textMöller, Stephanie. "Synthese und Untersuchung von Derivaten des Azobenzols mit Silananker zur Darstellung photoschaltbarer Oberflächen." Doctoral thesis, Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2013. http://hdl.handle.net/11858/00-1735-0000-0001-BAB3-A.
Full textSchweinhardt, Petra. "Neural correlates of clinical pain processing in neuropathic and inflammatory pain patients and comparison with experimental pain." Thesis, University of Oxford, 2006. http://ora.ox.ac.uk/objects/uuid:12e71d31-24f8-47e8-ba83-129575007644.
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