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DC Field | Value | Language |
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dc.contributor | Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP | |
dc.contributor.author | ALVES, Christiano R. R. | |
dc.contributor.author | NEVES, Willian das | |
dc.contributor.author | ALMEIDA, Ney R. de | |
dc.contributor.author | EICHELBERGER, Eric J. | |
dc.contributor.author | JANNIG, Paulo R. | |
dc.contributor.author | VOLTARELLI, Vanessa A. | |
dc.contributor.author | TOBIAS, Gabriel C. | |
dc.contributor.author | BECHARA, Luiz R. G. | |
dc.contributor.author | FARIA, Daniele de Paula | |
dc.contributor.author | ALVES, Maria J. N. | |
dc.contributor.author | HAGEN, Lars | |
dc.contributor.author | SHARMA, Animesh | |
dc.contributor.author | SLUPPHAUG, Geir | |
dc.contributor.author | MOREIRA, Jose B. N. | |
dc.contributor.author | WISLOFF, Ulrik | |
dc.contributor.author | HIRSHMAN, Michael F. | |
dc.contributor.author | NEGRAO, Carlos E. | |
dc.contributor.author | CASTRO JR., Gilberto de | |
dc.contributor.author | CHAMMAS, Roger | |
dc.contributor.author | SWOBODA, Kathryn J. | |
dc.contributor.author | RUAS, Jorge L. | |
dc.contributor.author | GOODYEAR, Laurie J. | |
dc.contributor.author | BRUM, Patricia C. | |
dc.date.accessioned | 2020-10-15T14:32:53Z | |
dc.date.available | 2020-10-15T14:32:53Z | |
dc.date.issued | 2020 | |
dc.identifier.citation | MOLECULAR METABOLISM, v.39, article ID 101012, 17p, 2020 | |
dc.identifier.issn | 2212-8778 | |
dc.identifier.uri | https://observatorio.fm.usp.br/handle/OPI/37713 | |
dc.description.abstract | Objective: We tested the hypothesis that exercise training would attenuate metabolic impairment in a model of severe cancer cachexia. Methods: We used multiple in vivo and in vitro methods to explore the mechanisms underlying the beneficial effects induced by exercise training in tumor-bearing rats. Results: Exercise training improved running capacity, prolonged lifespan, reduced oxidative stress, and normalized muscle mass and contractile function in tumor-bearing rats. An unbiased proteomic screening revealed COP9 signalosome complex subunit 2 (COPS2) as one of the most downregulated proteins in skeletal muscle at the early stage of cancer cachexia. Exercise training normalized muscle COPS2 protein expression in tumor-bearing rats and mice. Lung cancer patients with low endurance capacity had low muscle COPS2 protein expression as compared to agematched control subjects. To test whether decrease in COPS2 protein levels could aggravate or be an intrinsic compensatory mechanism to protect myotubes from cancer effects, we performed experiments in vitro using primary myotubes. COPS2 knockdown in human myotubes affected multiple cellular pathways, including regulation of actin cytoskeleton. Incubation of cancer-conditioned media in mouse myotubes decreased F-actin expression, which was partially restored by COPS2 knockdown. Direct repeat 4 (DR4) response elements have been shown to positively regulate gene expression. COPS2 overexpression decreased the DR4 activity in mouse myoblasts, and COPS2 knockdown inhibited the effects of cancer-conditioned media on DR4 activity. Conclusions: These studies demonstrated that exercise training may be an important adjuvant therapy to counteract cancer cachexia and uncovered novel mechanisms involving COPS2 to regulate myotube homeostasis in cancer cachexia. (C) 2020 The Author(s). | eng |
dc.description.sponsorship | FAPESP, Sao Paulo, BrazilFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2016/01478-0, 2014/03016-8, 2012/25240-1, 2012/02528-0, 2016/20187-6] | |
dc.description.sponsorship | Conselho Nacional de Pesquisa e Desenvolvimento (CNPq)National Council for Scientific and Technological Development (CNPq) [306261/2016-2] | |
dc.description.sponsorship | FAPESPFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [Sprint 16/50336-3, 2015/22814-5] | |
dc.description.sponsorship | Norwegian Health Association and the Research Council of Norway [275714] | |
dc.description.sponsorship | Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)National Council for Scientific and Technological Development (CNPq) [303573/2015-5] | |
dc.description.sponsorship | NICHDUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) [R01HD054599] | |
dc.description.sponsorship | BiogenBiogen | |
dc.description.sponsorship | Cure SMA | |
dc.description.sponsorship | NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01DK099511, R01DK101043] | |
dc.description.sponsorship | Joslin Diabetes Center DRC [P30 DK36836] | |
dc.description.sponsorship | Faculty of Medicine at the Norwegian University of Science and Technology (NTNU) | |
dc.description.sponsorship | Central Norway Regional Health Authority | |
dc.description.sponsorship | Norwegian research data archival system (NIRD)/Notur project [NN9036K] | |
dc.language.iso | eng | |
dc.publisher | ELSEVIER | eng |
dc.relation.ispartof | Molecular Metabolism | |
dc.rights | openAccess | eng |
dc.subject | Cancer cachexia | eng |
dc.subject | Muscle wasting | eng |
dc.subject | Atrophy | eng |
dc.subject | Endurance exercise | eng |
dc.subject | Response elements | eng |
dc.subject.other | heart-failure | eng |
dc.subject.other | skeletal-muscle | eng |
dc.subject.other | mitochondrial dysfunction | eng |
dc.subject.other | metabolic dysfunction | eng |
dc.subject.other | murine model | eng |
dc.subject.other | cachexia | eng |
dc.subject.other | heterodimers | eng |
dc.subject.other | atrophy | eng |
dc.subject.other | protein | eng |
dc.subject.other | members | eng |
dc.title | Exercise training reverses cancer-induced oxidative stress and decrease in muscle COPS2/ TRIP15/ALIEN | eng |
dc.type | article | eng |
dc.rights.holder | Copyright ELSEVIER | eng |
dc.identifier.doi | 10.1016/j.molmet.2020.101012 | |
dc.identifier.pmid | 32408015 | |
dc.subject.wos | Endocrinology & Metabolism | eng |
dc.type.category | original article | eng |
dc.type.version | publishedVersion | eng |
hcfmusp.author.external | ALVES, Christiano R. R.:Univ Sao Paulo, Sch Phys Educ & Sport, Sao Paulo, Brazil; Harvard Med Sch, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02115 USA; Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA | |
hcfmusp.author.external | ALMEIDA, Ney R. de:Univ Sao Paulo, Sch Phys Educ & Sport, Sao Paulo, Brazil | |
hcfmusp.author.external | EICHELBERGER, Eric J.:Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA | |
hcfmusp.author.external | JANNIG, Paulo R.:Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden | |
hcfmusp.author.external | VOLTARELLI, Vanessa A.:Univ Sao Paulo, Sch Phys Educ & Sport, Sao Paulo, Brazil | |
hcfmusp.author.external | TOBIAS, Gabriel C.:Univ Sao Paulo, Sch Phys Educ & Sport, Sao Paulo, Brazil | |
hcfmusp.author.external | BECHARA, Luiz R. G.:Univ Sao Paulo, Sch Phys Educ & Sport, Sao Paulo, Brazil | |
hcfmusp.author.external | HAGEN, Lars:Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway; NTNU, PROMEC, Prote & Modom Expt Core, Stjordal, Norway; Cent Norway Reg Hlth Author, Stjordal, Norway | |
hcfmusp.author.external | SHARMA, Animesh:Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway; NTNU, PROMEC, Prote & Modom Expt Core, Stjordal, Norway; Cent Norway Reg Hlth Author, Stjordal, Norway | |
hcfmusp.author.external | SLUPPHAUG, Geir:Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway; NTNU, PROMEC, Prote & Modom Expt Core, Stjordal, Norway; Cent Norway Reg Hlth Author, Stjordal, Norway | |
hcfmusp.author.external | MOREIRA, Jose B. N.:Norwegian Univ Sci & Technol, Dept Circulat & Med Imaging, KG Jebsen Ctr Exercise Med, Trondheim, Norway | |
hcfmusp.author.external | WISLOFF, Ulrik:Norwegian Univ Sci & Technol, Dept Circulat & Med Imaging, KG Jebsen Ctr Exercise Med, Trondheim, Norway | |
hcfmusp.author.external | HIRSHMAN, Michael F.:Harvard Med Sch, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02115 USA | |
hcfmusp.author.external | SWOBODA, Kathryn J.:Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA | |
hcfmusp.author.external | RUAS, Jorge L.:Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden | |
hcfmusp.author.external | GOODYEAR, Laurie J.:Harvard Med Sch, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02115 USA | |
hcfmusp.author.external | BRUM, Patricia C.:Univ Sao Paulo, Sch Phys Educ & Sport, Sao Paulo, Brazil | |
hcfmusp.description.articlenumber | 101012 | |
hcfmusp.description.volume | 39 | |
hcfmusp.origem | WOS | |
hcfmusp.origem.id | WOS:000562967300003 | |
hcfmusp.origem.id | 2-s2.0-85085761815 | |
hcfmusp.publisher.city | AMSTERDAM | eng |
hcfmusp.publisher.country | NETHERLANDS | eng |
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dc.description.index | MEDLINE | eng |
hcfmusp.citation.scopus | 20 | - |
hcfmusp.scopus.lastupdate | 2024-03-29 | - |
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