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Role of PARP activity in lung cancer-induced cachexia: Effects on muscle oxidative stress, proteolysis, anabolic markers, and phenotype

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dc.contributor.author Chacón Cabrera, Alba, 1988-
dc.contributor.author Mateu-Jimenez, Mercè
dc.contributor.author Langohr, Klaus
dc.contributor.author Fermoselle Pérez, Clara, 1985-
dc.contributor.author García-Arumí, Elena
dc.contributor.author Andreu, Antoni
dc.contributor.author Yélamos López, José
dc.contributor.author Barreiro Portela, Esther
dc.date.accessioned 2018-03-14T09:27:19Z
dc.date.issued 2017
dc.identifier.citation Chacon-Cabrera A, Mateu-Jimenez M, Langohr K, Fermoselle C, García-Arumí E, Andreu AL. Et al. Role of PARP activity in lung cancer-induced cachexia: Effects on muscle oxidative stress, proteolysis, anabolic markers, and phenotype. J Cell Physiol. 2017 Dec;232(12):3744-61. DOI: 10.1002/jcp.25851
dc.identifier.issn 1097-4652
dc.identifier.uri http://hdl.handle.net/10230/34097
dc.description.abstract Strategies to treat cachexia are still at its infancy. Enhanced muscle protein breakdown and ubiquitin-proteasome system are common features of cachexia associated with chronic conditions including lung cancer (LC). Poly(ADP-ribose) polymerases (PARP), which play a major role in chromatin structure regulation, also underlie maintenance of muscle metabolism and body composition. We hypothesized that protein catabolism, proteolytic markers, muscle fiber phenotype, and muscle anabolism may improve in respiratory and limb muscles of LC-cachectic Parp-1-deficient (Parp-1-/- ) and Parp-2-/- mice. In diaphragm and gastrocnemius of LC (LP07 adenocarcinoma) bearing mice (wild type, Parp-1-/- , and Parp-2-/- ), PARP activity (ADP-ribose polymers, pADPr), redox balance, muscle fiber phenotype, apoptotic nuclei, tyrosine release, protein ubiquitination, muscle-specific E3 ligases, NF-κB signaling pathway, markers of muscle anabolism (Akt, mTOR, p70S6K, and mitochondrial DNA) were evaluated along with body and muscle weights, and limb muscle force. Compared to wild type cachectic animals, in both respiratory and limb muscles of Parp-1-/- and Parp-2-/- cachectic mice: cancer induced-muscle wasting characterized by increased PARP activity, protein oxidation, tyrosine release, and ubiquitin-proteasome system (total protein ubiquitination, atrogin-1, and 20S proteasome C8 subunit) were blunted, the reduction in contractile myosin and atrophy of the fibers was attenuated, while no effects were seen in other structural features (inflammatory cells, internal or apoptotic nuclei), and markers of muscle anabolism partly improved. Activation of either PARP-1 or -2 is likely to play a role in muscle protein catabolism via oxidative stress, NF-κB signaling, and enhanced proteasomal degradation in cancer-induced cachexia. Therapeutic potential of PARP activity inhibition deserves attention
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Wiley
dc.relation.ispartof Journal of Cellular Physiology. 2017 Dec;232(12):3744-61
dc.rights This is the peer reviewed version of the following article: Chacon-Cabrera A, Mateu-Jimenez M, Langohr K, Fermoselle C, García-Arumí E, Andreu AL. Et al. Role of PARP activity in lung cancer-induced cachexia: Effects on muscle oxidative stress, proteolysis, anabolic markers, and phenotype. J Cell Physiol. 2017 Dec;232(12):3744-3761, which has been published in final form at http://dx.doi.org/10.1002/jcp.25851. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
dc.subject.other Caquèxia
dc.subject.other Pulmons -- Càncer
dc.subject.other Fenotip
dc.title Role of PARP activity in lung cancer-induced cachexia: Effects on muscle oxidative stress, proteolysis, anabolic markers, and phenotype
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1002/jcp.25851
dc.subject.keyword PARP activity
dc.subject.keyword Parp-1−/− and Parp-2−/− mice
dc.subject.keyword Cancer-induced cachexia
dc.subject.keyword Muscle anabolism and catabolism and mitochondrial content
dc.subject.keyword Muscle atrophy and myosin loss
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/acceptedVersion

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