{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T17:08:08Z","timestamp":1765040888281,"version":"build-2065373602"},"reference-count":42,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2018,12,31]],"date-time":"2018-12-31T00:00:00Z","timestamp":1546214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cardiac dysfunction secondary to cancer may exert a negative impact in patients\u2019 tolerance to therapeutics, quality of life, and survival. The aim of this study was to evaluate the potential therapeutic effect of exercise training on the heart in the setting of cancer, after diagnosis. Thus, the molecular pathways harbored in heart mitochondria from a murine model of chemically-induced urothelial carcinoma submitted to 8-weeks of high intensity treadmill exercise were characterized using mass spectrometry-based proteomics. Data highlight the protective effects of high intensity exercise training in preventing left ventricle diastolic dysfunction, fibrosis, and structural derangement observed in tumor-bearing mice. At the mitochondrial level, exercise training counteracted the lower ability to produce ATP observed in the heart of animals with urothelial carcinoma and induced the up-regulation of fatty acid oxidation and down-regulation of the biological process \u201ccardiac morphogenesis\u201d. Taken together, our data support the prescription of exercise training after cancer diagnosis for the management of disease-related cardiac dysfunction.<\/jats:p>","DOI":"10.3390\/ijms20010127","type":"journal-article","created":{"date-parts":[[2018,12,31]],"date-time":"2018-12-31T07:22:30Z","timestamp":1546240950000},"page":"127","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Exercise Training Impacts Cardiac Mitochondrial Proteome Remodeling in Murine Urothelial Carcinoma"],"prefix":"10.3390","volume":"20","author":[{"given":"Rita","family":"Ferreira","sequence":"first","affiliation":[{"name":"QOPNA-Qu\u00edmica Org\u00e2nica, Produtos Naturais e Agroalimentares, Departamento de Qu\u00edmica, Universidade de Aveiro, Campus Universit\u00e1rio de Santiago, 3810-193 Aveiro, Portugal"}]},{"given":"Maria Jo\u00e3o","family":"Neuparth","sequence":"additional","affiliation":[{"name":"CIAFEL-Centro de Investiga\u00e7\u00e3o em Actividade F\u00edsica, Sa\u00fade e Lazer, Faculdade de Desporto, Universidade do Porto, R. Dr. Pl\u00e1cido da Costa 91, 4200-450 Porto, Portugal"}]},{"given":"Rita","family":"Nogueira-Ferreira","sequence":"additional","affiliation":[{"name":"iBiMED-Institute of Biomedicine, Departamento de Ci\u00eancias M\u00e9dicas, Universidade de Aveiro, Agra do Crasto, 3810-193 Aveiro, Portugal"},{"name":"Departamento de Cirurgia e Fisiologia, Faculdade de Medicina, Universidade do Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"given":"Sandra","family":"Magalh\u00e3es","sequence":"additional","affiliation":[{"name":"iBiMED-Institute of Biomedicine, Departamento de Ci\u00eancias M\u00e9dicas, Universidade de Aveiro, Agra do Crasto, 3810-193 Aveiro, Portugal"}]},{"given":"Miguel","family":"Aroso","sequence":"additional","affiliation":[{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4020-135 Porto, Portugal"},{"name":"INEB-Instituto de Engenharia Biom\u00e9dica, Universidade do Porto, Rua Alfredo Allen, 208, 4200-180 Porto, Portugal"}]},{"given":"Jos\u00e9 Ant\u00f3nio","family":"Bovolini","sequence":"additional","affiliation":[{"name":"CIAFEL-Centro de Investiga\u00e7\u00e3o em Actividade F\u00edsica, Sa\u00fade e Lazer, Faculdade de Desporto, Universidade do Porto, R. Dr. Pl\u00e1cido da Costa 91, 4200-450 Porto, Portugal"}]},{"given":"L\u00facio","family":"Lara Santos","sequence":"additional","affiliation":[{"name":"Grupo de Patologia e Terap\u00eautica Experimental, Instituto Portugu\u00eas de Oncologia, R. Dr. Ant\u00f3nio Bernardino de Almeida, 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9519-4044","authenticated-orcid":false,"given":"Paula","family":"Oliveira","sequence":"additional","affiliation":[{"name":"CITAB-Centre for the Research and Technology of Agro-Environmental and Biological Sciences, Departamento de Ci\u00eancias Veterin\u00e1rias, Universidade de Tr\u00e1s-os-Montes e Alto Douro, Quinta de Prados, 5001-911 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3636-5805","authenticated-orcid":false,"given":"Rui","family":"Vitorino","sequence":"additional","affiliation":[{"name":"iBiMED-Institute of Biomedicine, Departamento de Ci\u00eancias M\u00e9dicas, Universidade de Aveiro, Agra do Crasto, 3810-193 Aveiro, Portugal"},{"name":"Departamento de Cirurgia e Fisiologia, Faculdade de Medicina, Universidade do Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"given":"Daniel","family":"Moreira-Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"CIAFEL-Centro de Investiga\u00e7\u00e3o em Actividade F\u00edsica, Sa\u00fade e Lazer, Faculdade de Desporto, Universidade do Porto, R. Dr. Pl\u00e1cido da Costa 91, 4200-450 Porto, Portugal"},{"name":"Departamento de Cirurgia e Fisiologia, Faculdade de Medicina, Universidade do Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2018,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1093\/annonc\/mdu085","article-title":"Early recognition of malnutrition and cachexia in the cancer patient: A position paper of a European School of Oncology Task Force","volume":"25","author":"Aapro","year":"2014","journal-title":"Ann. Oncol"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1038\/nrc3829","article-title":"Cancer cachexia: Understanding the molecular basis","volume":"14","author":"Argiles","year":"2014","journal-title":"Nat. Rev. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1016\/j.ijcard.2013.03.133","article-title":"Cardioncology: State of the heart","volume":"168","author":"Todaro","year":"2013","journal-title":"Int. J. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1038\/ncponc1226","article-title":"Cancer fatigue syndrome reflects clinically non-overt heart failure: An approach towards onco-cardiology","volume":"5","author":"Schunemann","year":"2008","journal-title":"Nat. Clin. Pract. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.abb.2014.12.026","article-title":"Endurance training prevents TWEAK but not myostatin-mediated cardiac remodelling in cancer cachexia","volume":"567","author":"Padrao","year":"2015","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_6","first-page":"1321","article-title":"Evidence for cardiac atrophic remodeling in cancer-induced cachexia in mice","volume":"39","author":"Tian","year":"2011","journal-title":"Int. J. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/nrc990","article-title":"The endothelin axis: Emerging role in cancer","volume":"3","author":"Nelson","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1874","DOI":"10.1136\/heartjnl-2015-307848","article-title":"Cardiovascular biomarkers in patients with cancer and their association with all-cause mortality","volume":"101","author":"Pavo","year":"2015","journal-title":"Heart"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1159\/000011957","article-title":"Human small cell lung cancer cells produce brain natriuretic peptide","volume":"56","author":"Ohsaki","year":"1999","journal-title":"Oncology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1016\/j.clinbiochem.2013.04.029","article-title":"Highly-sensitive troponin I is increased in patients with gynecological cancers","volume":"46","author":"Danese","year":"2013","journal-title":"Clin. Biochem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.pcad.2014.10.001","article-title":"Exercise Training in Patients with Heart Disease: Review of Beneficial Effects and Clinical Recommendations","volume":"57","author":"Gielen","year":"2015","journal-title":"Prog. Cardiovasc. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1007\/s00395-014-0454-5","article-title":"Unraveling the exercise-related proteome signature in heart","volume":"110","author":"Ferreira","year":"2015","journal-title":"Basic Res. Cardiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.molmed.2018.06.002","article-title":"Exercise Training as Therapy for Cancer-Induced Cardiac Cachexia","volume":"24","author":"Antunes","year":"2018","journal-title":"Trends Mol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.abb.2018.03.013","article-title":"Exercise training protects against cancer-induced cardiac remodeling in an animal model of urothelial carcinoma","volume":"645","author":"Vitorino","year":"2018","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1021\/pr4011926","article-title":"Lifelong exercise training modulates cardiac mitochondrial phosphoproteome in rats","volume":"13","author":"Ferreira","year":"2014","journal-title":"J. Proteome Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Brailoiu, E., Deliu, E., Sporici, R.A., and Brailoiu, G.C. (2015). Irisin evokes bradycardia by activating cardiac-projecting neurons of nucleus ambiguus. Physiol. Rep., 3.","DOI":"10.14814\/phy2.12419"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.yjmcc.2014.04.004","article-title":"S-nitrosylation of TRIM72 mends the broken heart: A molecular modifier-mediated cardioprotection","volume":"72","author":"Wang","year":"2014","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_18","first-page":"2","article-title":"Experimental bladder carcinogenesis-rodent models","volume":"28","author":"Oliveira","year":"2006","journal-title":"Exp. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1016\/j.biocel.2013.04.014","article-title":"Bladder cancer-induced skeletal muscle wasting: Disclosing the role of mitochondria plasticity","volume":"45","author":"Padrao","year":"2013","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.lfs.2010.12.010","article-title":"Myocardial dysfunction in an animal model of cancer cachexia","volume":"88","author":"Xu","year":"2011","journal-title":"Life Sci."},{"key":"ref_21","first-page":"347","article-title":"Cardiac alterations in cancer-induced cachexia in mice","volume":"37","author":"Tian","year":"2010","journal-title":"Int. J. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/B978-0-12-800180-6.00003-7","article-title":"New Insights into the Roles of Xin Repeat-Containing Proteins in Cardiac Development, Function, and Disease","volume":"310","author":"Wang","year":"2014","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2566","DOI":"10.2741\/4072","article-title":"Xin proteins and intercalated disc maturation, signaling and diseases","volume":"17","author":"Wang","year":"2012","journal-title":"Front. Biosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.yexcr.2016.09.008","article-title":"Sarcomeric lesions and remodeling proximal to intercalated disks in overload-induced cardiac hypertrophy","volume":"348","author":"Kebir","year":"2016","journal-title":"Exp. Cell Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.talanta.2013.04.026","article-title":"Mitochondria proteome profiling: A comparative analysis between gel- and gel-free approaches","volume":"115","author":"Ferreira","year":"2013","journal-title":"Talanta"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.jprot.2011.04.025","article-title":"Characterization of mitochondrial proteome in a severe case of ETF-QO deficiency","volume":"75","author":"Rocha","year":"2011","journal-title":"J. Proteomics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2625","DOI":"10.1161\/CIRCULATIONAHA.111.060376","article-title":"Can exercise teach us how to treat heart disease?","volume":"126","author":"Mann","year":"2012","journal-title":"Circulation"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.metabol.2018.07.004","article-title":"Sugar or fat: The metabolic choice of the trained heart","volume":"87","author":"Ferreira","year":"2018","journal-title":"Metabolism"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1161\/CIRCHEARTFAILURE.114.001469","article-title":"Energy metabolic reprogramming in the hypertrophied and early stage failing heart: A multisystems approach","volume":"7","author":"Lai","year":"2014","journal-title":"Circ. Heart Fail."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"H144","DOI":"10.1152\/ajpheart.01278.2008","article-title":"Exercise training induces a cardioprotective phenotype and alterations in cardiac subsarcolemmal and intermyofibrillar mitochondrial proteins","volume":"297","author":"Kavazis","year":"2009","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.1249\/MSS.0000000000000664","article-title":"Updating ACSM\u2019s Recommendations for Exercise Preparticipation Health Screening","volume":"47","author":"Riebe","year":"2015","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Vasconcelos-Nobrega, C., Pinto-Leite, R., Arantes-Rodrigues, R., Ferreira, R., Brochado, P., Cardoso, M.L., Palmeira, C., Salvador, A., Guedes-Teixeira, C.I., and Colaco, A. (2013). In vivo and in vitro effects of RAD001 on bladder cancer. Urol. Oncol.","DOI":"10.1016\/j.urolonc.2011.11.002"},{"key":"ref_33","unstructured":"Snedecor, G.W., and Cochran, W.G. (1989). Statistical Methods, Iowa State University Press. [8th ed.]."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1152\/japplphysiol.00231.2002","article-title":"Intensity-controlled treadmill running in mice: Cardiac and skeletal muscle hypertrophy","volume":"93","author":"Kemi","year":"2002","journal-title":"J. Appl. Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3885","DOI":"10.1113\/JP270685","article-title":"Intermittent cardiac overload results in adaptive hypertrophy and provides protection against left ventricular acute pressure overload insult","volume":"593","author":"Fonseca","year":"2015","journal-title":"J. Physiol."},{"key":"ref_36","unstructured":"Forbes, D.B.H., Kostomitsopulos, N., Moore, G., and Perretta, G. (2018, December 29). Euroguide: On the Accommodation and Care of Animals Used for Experimental and Other Scientific Purposes. Available online: http:\/\/www.felasa.eu\/about-us\/library\/."},{"key":"ref_37","first-page":"3221","article-title":"The effects of sirolimus on urothelial lesions chemically induced in ICR mice by BBN","volume":"29","author":"Oliveira","year":"2009","journal-title":"Anticancer Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1007\/s00421-011-2100-3","article-title":"Effect of lifestyle on age-related mitochondrial protein oxidation in mice cardiac muscle","volume":"112","author":"Padrao","year":"2012","journal-title":"Eur. J. Appl. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/sj.bjp.0705038","article-title":"Tacrolimus and sirolimus decrease oxidative phosphorylation of isolated rat kidney mitochondria","volume":"138","author":"Simon","year":"2003","journal-title":"Br. J. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1042\/bj1250115","article-title":"Regulation of adipose tissue pyruvate dehydrogenase by insulin and other hormones","volume":"125","author":"Coore","year":"1971","journal-title":"Biochem. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/227680a0","article-title":"Cleavage of structural proteins during the assembly of the head of bacteriophage T4","volume":"227","author":"Laemmli","year":"1970","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1074\/mcp.M500061-MCP200","article-title":"Exponentially modified protein abundance index (emPAI) for estimation of absolute protein amount in proteomics by the number of sequenced peptides per protein","volume":"4","author":"Ishihama","year":"2005","journal-title":"Mol. Cell Proteomics"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/1\/127\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:36:47Z","timestamp":1760197007000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/1\/127"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,31]]},"references-count":42,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,1]]}},"alternative-id":["ijms20010127"],"URL":"https:\/\/doi.org\/10.3390\/ijms20010127","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2018,12,31]]}}}