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dc.contributor.author
Fermoselle, Clara
dc.contributor.author
García Arumí, Elena
dc.contributor.author
Puig Vilanova, Ester
dc.contributor.author
Andreu, Antoni L.
dc.contributor.author
Urtreger, Alejandro Jorge
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dc.contributor.author
Bal, Elisa Dora
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dc.contributor.author
Tejedor, Alberto
dc.contributor.author
Puente Maestu, Luís
dc.contributor.author
Barreiro, Esther
dc.date.available
2017-02-10T19:29:39Z
dc.date.issued
2013-09
dc.identifier.citation
Fermoselle, Clara; García Arumí, Elena; Puig Vilanova, Ester; Andreu, Antoni L.; Urtreger, Alejandro Jorge; et al.; Mitochondrial dysfunction and therapeutic approaches in respiratory and limb muscles of cancer cachectic mice; Wiley; Experimental Physiology.; 98; 9; 9-2013; 1349-1365
dc.identifier.issn
0958-0670
dc.identifier.uri
http://hdl.handle.net/11336/12872
dc.description.abstract
Abnormalities in mitochondrial content, morphology, and function were reported in several muscle wasting conditions. We specifically explored whether experimental cancer-induced cachexia may alter mitochondrial respiratory chain (MRC) complexes and oxygen uptake in respiratory and peripheral muscles, and whether signaling pathways, proteasome, and oxidative stress may influence that process. We evaluated complex I, II, and IV enzyme activities (specific activity assays) and MRC oxygen consumption (polarographic measurements) in diaphragm and gastrocnemius of cachectic mice bearing the LP07 lung tumor with and without treatment with N-acetylcysteine, bortezomib, and nuclear factor (NF)-kB (sulfasalazine) and mitogen-activated protein kinases (MAPK, U0126) inhibitors, n=10/group, all groups. Whole body and muscle weights and limb muscle force were also assessed in all rodents at baseline and after one month. Compared to controls, cancer cachectic mice showed a significant reduction in body weight gain, smaller sizes of diaphragm and gastrocnemius, lower muscle strength, and decreased activity of complexes I, II, and IV, and oxygen consumption in both muscles. Blockade of NF-kB and MAPK actions restored muscle mass loss and force, and MRC dysfunction in both muscles, while partly reducing tumor burden. Antioxidants improved mitochondrial oxygen uptake without eliciting significant effects on muscle mass loss and force or tumor size, whereas the proteasome inhibitor reduced tumor burden without significantly influencing muscle mass and strength or mitochondrial function. In conclusion, NF-kb and MAPK signaling pathways modulate muscle mass and performance and MRC function of respiratory and limb muscles in this model of experimental cancer cachexia, thus offering targets for therapeutic intervention.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Wiley
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Lung Cancer Cachexia
dc.subject
Mitochondrial Respiratory Chain
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Oxygen Consumption
dc.subject.classification
Otros Tópicos Biológicos
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dc.subject.classification
Ciencias Biológicas
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dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
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dc.title
Mitochondrial dysfunction and therapeutic approaches in respiratory and limb muscles of cancer cachectic mice
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-02-09T18:22:50Z
dc.journal.volume
98
dc.journal.number
9
dc.journal.pagination
1349-1365
dc.journal.pais
Reino Unido
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dc.journal.ciudad
Londres
dc.description.fil
Fil: Fermoselle, Clara. Universitat Pompeu Fabra; España
dc.description.fil
Fil: García Arumí, Elena. Instituto de Salud Carlos III; España. Centro de Investigacion Biomédica en Red de Enfermedades Raras; España
dc.description.fil
Fil: Puig Vilanova, Ester. Universitat Pompeu Fabra; España
dc.description.fil
Fil: Andreu, Antoni L.. Centro de Investigacion Biomédica en Red de Enfermedades Raras; España. Universitari Vall d’Hebron; España
dc.description.fil
Fil: Urtreger, Alejandro Jorge. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncologia "Angel H. Roffo"; Argentina
dc.description.fil
Fil: Bal, Elisa Dora. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncologia "Angel H. Roffo"; Argentina
dc.description.fil
Fil: Tejedor, Alberto. Universidad Complutense de Madrid; España
dc.description.fil
Fil: Puente Maestu, Luís. Universidad Complutense de Madrid; España
dc.description.fil
Fil: Barreiro, Esther. Universitat Pompeu Fabra; España
dc.journal.title
Experimental Physiology.
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1113/expphysiol.2013.072496/abstract
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1113/expphysiol.2013.072496
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