Mitochondrial dysfunction and therapeutic approaches in respiratory and limb muscles of cancer cachectic mice

Autores
Fermoselle, Clara; García Arumí, Elena; Puig Vilanova, Ester; Andreu, Antoni L.; Urtreger, Alejandro Jorge; Bal, Elisa Dora; Tejedor, Alberto; Puente Maestu, Luís; Barreiro, Esther
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Fermoselle, Clara. Universitat Pompeu Fabra; España
Fil: García Arumí, Elena. Instituto de Salud Carlos III; España. Centro de Investigacion Biomédica en Red de Enfermedades Raras; España
Fil: Puig Vilanova, Ester. Universitat Pompeu Fabra; España
Fil: Andreu, Antoni L.. Centro de Investigacion Biomédica en Red de Enfermedades Raras; España. Universitari Vall d’Hebron; España
Fil: Urtreger, Alejandro Jorge. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncologia "Angel H. Roffo"; Argentina
Fil: Bal, Elisa Dora. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncologia "Angel H. Roffo"; Argentina
Fil: Tejedor, Alberto. Universidad Complutense de Madrid; España
Fil: Puente Maestu, Luís. Universidad Complutense de Madrid; España
Fil: Barreiro, Esther. Universitat Pompeu Fabra; España
Materia
Lung Cancer Cachexia
Mitochondrial Respiratory Chain
Oxygen Consumption
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/12872
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/12872
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Mitochondrial dysfunction and therapeutic approaches in respiratory and limb muscles of cancer cachectic miceFermoselle, ClaraGarcía Arumí, ElenaPuig Vilanova, EsterAndreu, Antoni L.Urtreger, Alejandro JorgeBal, Elisa DoraTejedor, AlbertoPuente Maestu, LuísBarreiro, EstherLung Cancer CachexiaMitochondrial Respiratory ChainOxygen Consumptionhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Abnormalities 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.Fil: Fermoselle, Clara. Universitat Pompeu Fabra; EspañaFil: García Arumí, Elena. Instituto de Salud Carlos III; España. Centro de Investigacion Biomédica en Red de Enfermedades Raras; EspañaFil: Puig Vilanova, Ester. Universitat Pompeu Fabra; EspañaFil: Andreu, Antoni L.. Centro de Investigacion Biomédica en Red de Enfermedades Raras; España. Universitari Vall d’Hebron; EspañaFil: Urtreger, Alejandro Jorge. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncologia "Angel H. Roffo"; ArgentinaFil: Bal, Elisa Dora. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncologia "Angel H. Roffo"; ArgentinaFil: Tejedor, Alberto. Universidad Complutense de Madrid; EspañaFil: Puente Maestu, Luís. Universidad Complutense de Madrid; EspañaFil: Barreiro, Esther. Universitat Pompeu Fabra; EspañaWiley2013-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/12872Fermoselle, 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; 1349-13650958-0670enginfo:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1113/expphysiol.2013.072496/abstractinfo:eu-repo/semantics/altIdentifier/doi/10.1113/expphysiol.2013.072496info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:22:38Zoai:ri.conicet.gov.ar:11336/12872instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:22:38.707CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Mitochondrial dysfunction and therapeutic approaches in respiratory and limb muscles of cancer cachectic mice
title Mitochondrial dysfunction and therapeutic approaches in respiratory and limb muscles of cancer cachectic mice
spellingShingle Mitochondrial dysfunction and therapeutic approaches in respiratory and limb muscles of cancer cachectic mice
Fermoselle, Clara
Lung Cancer Cachexia
Mitochondrial Respiratory Chain
Oxygen Consumption
title_short Mitochondrial dysfunction and therapeutic approaches in respiratory and limb muscles of cancer cachectic mice
title_full Mitochondrial dysfunction and therapeutic approaches in respiratory and limb muscles of cancer cachectic mice
title_fullStr Mitochondrial dysfunction and therapeutic approaches in respiratory and limb muscles of cancer cachectic mice
title_full_unstemmed Mitochondrial dysfunction and therapeutic approaches in respiratory and limb muscles of cancer cachectic mice
title_sort Mitochondrial dysfunction and therapeutic approaches in respiratory and limb muscles of cancer cachectic mice
dc.creator.none.fl_str_mv Fermoselle, Clara
García Arumí, Elena
Puig Vilanova, Ester
Andreu, Antoni L.
Urtreger, Alejandro Jorge
Bal, Elisa Dora
Tejedor, Alberto
Puente Maestu, Luís
Barreiro, Esther
author Fermoselle, Clara
author_facet Fermoselle, Clara
García Arumí, Elena
Puig Vilanova, Ester
Andreu, Antoni L.
Urtreger, Alejandro Jorge
Bal, Elisa Dora
Tejedor, Alberto
Puente Maestu, Luís
Barreiro, Esther
author_role author
author2 García Arumí, Elena
Puig Vilanova, Ester
Andreu, Antoni L.
Urtreger, Alejandro Jorge
Bal, Elisa Dora
Tejedor, Alberto
Puente Maestu, Luís
Barreiro, Esther
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Lung Cancer Cachexia
Mitochondrial Respiratory Chain
Oxygen Consumption
topic Lung Cancer Cachexia
Mitochondrial Respiratory Chain
Oxygen Consumption
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 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.
Fil: Fermoselle, Clara. Universitat Pompeu Fabra; España
Fil: García Arumí, Elena. Instituto de Salud Carlos III; España. Centro de Investigacion Biomédica en Red de Enfermedades Raras; España
Fil: Puig Vilanova, Ester. Universitat Pompeu Fabra; España
Fil: Andreu, Antoni L.. Centro de Investigacion Biomédica en Red de Enfermedades Raras; España. Universitari Vall d’Hebron; España
Fil: Urtreger, Alejandro Jorge. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncologia "Angel H. Roffo"; Argentina
Fil: Bal, Elisa Dora. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncologia "Angel H. Roffo"; Argentina
Fil: Tejedor, Alberto. Universidad Complutense de Madrid; España
Fil: Puente Maestu, Luís. Universidad Complutense de Madrid; España
Fil: Barreiro, Esther. Universitat Pompeu Fabra; España
description 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.
publishDate 2013
dc.date.none.fl_str_mv 2013-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/12872
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
0958-0670
url http://hdl.handle.net/11336/12872
identifier_str_mv 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
0958-0670
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1113/expphysiol.2013.072496/abstract
info:eu-repo/semantics/altIdentifier/doi/10.1113/expphysiol.2013.072496
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.48226

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