Molecular mechanisms involved in the process of muscle wasting : human and animal studies

Mostra el registre complet Registre parcial de l'ítem

• dc.contributor.author Fermoselle Pérez, Clara
• dc.contributor.other Barreiro Portela, Esther
• dc.contributor.other Universitat Pompeu Fabra. Departament de Ciències Experimentals i de la Salut
• dc.date.accessioned 2024-03-16T02:34:03Z
• dc.date.available 2024-03-16T02:34:03Z
• dc.date.issued 2013-06-18T15:41:48Z
• dc.date.issued 2013-06-18T15:41:48Z
• dc.date.issued 2012-11-26
• dc.date.modified 2024-03-15T10:57:17Z
• dc.description.abstract Muscle dysfunction and muscle wasting are major systemic manifestations of chronic conditions such as Chronic Obstructive Pulmonary Disease (COPD) and cancer. Several biological mechanisms contribute to such a dysfunction. Our objectives were to identify cellular and molecular mechanisms involved in the respiratory and peripheral muscle dysfunction of cachexia models associated with chronic respiratory conditions. The diaphragm and gastrocnemius of mice [emphysema and lung cancer (LC) models] and the vastus lateralis of severe COPD patients were studied with their respective healthy controls. Muscle structure was analyzed in the animal LC model and in the COPD human model. Several biological markers were studied: proteolysis markers, signaling pathways related to proteolysis, redox balance and inflammation. Mitochondrial respiratory chain was also explored in the LC mice model. In all three models the cachectic subjects were identified using total body weight. In patients, fat-free mass index was also identified. In the mouse models, muscle weights were also determined. They were decreased in all cachectic animals compared to the controls. Muscle structure was affected in the cachectic subjects: LC cachectic mice showed a decrease in both type I and II fibers size, while muscle-wasted COPD patients showed a decrease in type II fiber sizes and in proportions of type I fibers. Proportions of myofiber abnormalities were greater in both LC cachectic animals and muscle-wasted COPD patients. Only LC cachectic mice showed higher levels of IFNγ in the diaphragm. Oxidative stress, proteolysis markers and NFκB pathway were enhanced in the muscles of the cachectic subjects in the three models. Mitogen-activated protein kinases (MAPK) and forkhead box (FoxO) signaling pathways were enhanced in the muscles of the cachectic mice. Myogenin levels were reduced in the muscles of all three models. Myostatin levels were greater in the muscles of the cachectic mice. Mitochondrial function was depressed in both respiratory and limb muscles of the LC cachectic mice. We conclude that enhanced protein catabolism and mitochondrial dysfunction occurs in the muscles of these cachexia models (both patients and animals). Major signaling pathways such as NF-kB and FoxO are involved in this process. These findings offer future therapeutic strategies in cachexia associated with chronic respiratory conditions.
• dc.description.abstract Programa de doctorat en Biomedicina
• dc.format 77 p.
• dc.format application/pdf
• dc.format application/pdf
• dc.identifier http://hdl.handle.net/10803/116734
• dc.identifier B. 16714-2013
• dc.identifier.uri http://hdl.handle.net/10230/20688
• dc.language.iso eng
• dc.publisher Universitat Pompeu Fabra
• dc.rights ADVERTIMENT. L'accés als continguts d'aquesta tesi doctoral i la seva utilització ha de respectar els drets de la persona autora. Pot ser utilitzada per a consulta o estudi personal, així com en activitats o materials d'investigació i docència en els termes establerts a l'art. 32 del Text Refós de la Llei de Propietat Intel·lectual (RDL 1/1996). Per altres utilitzacions es requereix l'autorització prèvia i expressa de la persona autora. En qualsevol cas, en la utilització dels seus continguts caldrà indicar de forma clara el nom i cognoms de la persona autora i el títol de la tesi doctoral. No s'autoritza la seva reproducció o altres formes d'explotació efectuades amb finalitats de lucre ni la seva comunicació pública des d'un lloc aliè al servei TDX. Tampoc s'autoritza la presentació del seu contingut en una finestra o marc aliè a TDX (framing). Aquesta reserva de drets afecta tant als continguts de la tesi com als seus resums i índexs.
• dc.rights info:eu-repo/semantics/openAccess
• dc.source TDX (Tesis Doctorals en Xarxa)
• dc.subject.keyword COPD
• dc.subject.keyword Lung cancer
• dc.subject.keyword Cachexia
• dc.subject.keyword Muscle wasting
• dc.subject.keyword MAPK
• dc.subject.keyword NFKB
• dc.subject.keyword Myostatin
• dc.subject.keyword Mitochondrial dysfunction
• dc.subject.keyword EPOC
• dc.subject.keyword Cáncer de pulmón
• dc.subject.keyword Caquéxia
• dc.subject.keyword Desgaste muscular
• dc.subject.keyword Miostatina
• dc.subject.keyword Disfunción mitocondrial
• dc.subject.keyword 616.2
• dc.title Molecular mechanisms involved in the process of muscle wasting : human and animal studies
• dc.type info:eu-repo/semantics/doctoralThesis
• dc.type info:eu-repo/semantics/publishedVersion