Cancer-induced muscle atrophy is determined by intrinsic muscle oxidative capacity

Autor(es):Mostrar menos -

Alves, Christiano R. R. ^{[1, 2]} ; Eichelberger, Eric J. ^[2] ; das Neves, Willian ^[1] ; Ribeiro, Marcio A. C. ^[3] ; Bechara, Luiz R. G. ^[3] ; Voltarelli, Vanessa A. ^[1] ; de Almeida, Ney R. ^[1] ; Hagen, Lars ^{[4, 5, 6]} ; Sharma, Animesh ^{[4, 5, 6]} ; Ferreira, Julio C. B. ^[3] ; Swoboda, Kathryn J. ^[2] ; Slupphaug, Geir ^{[4, 5, 6]} ; Brum, Patricia C. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Phys Educ & Sport, Sao Paulo - Brazil

^[2] Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 - USA

^[3] Univ Sao Paulo, Inst Biomed Sci, Sao Paulo - Brazil

^[4] Cent Norway Reg Hlth Author, Trondheim - Norway

^[5] NTNU Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim - Norway

^[6] NTNU, PROMEC Prote & Mod Expt Core, Trondheim - Norway

• Tipo de documento: Artigo Científico
• Fonte: FASEB JOURNAL; v. 35, n. 7 JUL 2021.
• Citações Web of Science: 0

Resumo

We tested the hypothesis that cancer cachexia progression would induce oxidative post-translational modifications (Ox-PTMs) associated with skeletal muscle wasting, with different responses in muscles with the prevalence of glycolytic and oxidative fibers. We used cysteine-specific isotopic coded affinity tags (OxICAT) and gel-free mass spectrometry analysis to investigate the cysteine Ox-PTMs profile in the proteome of both plantaris (glycolytic) and soleus (oxidative) muscles in tumor-bearing and control rats. Histological analysis revealed muscle atrophy in type II fibers in plantaris muscle, with no changes in plantaris type I fibers and no differences in both soleus type I and II fibers in tumor-bearing rats when compared to healthy controls. Tumor progression altered the Ox-PTMs profile in both plantaris and soleus. However, pathway analysis including the differentially oxidized proteins revealed tricarboxylic acid cycle and oxidative phosphorylation as main affected pathways in plantaris muscle from tumor-bearing rats, while the same analysis did not show main metabolic pathways affected in the soleus muscle. In addition, cancer progression affected several metabolic parameters such as ATP levels and markers of oxidative stress associated with muscle atrophy in plantaris muscle, but not in soleus. However, isolated soleus from tumor-bearing rats had a reduced force production capacity when compared to controls. These novel findings demonstrate that tumor-bearing rats have severe muscle atrophy exclusively in glycolytic fibers. Cancer progression is associated with cysteine Ox-PTMs in the skeletal muscle, but these modifications affect different pathways in a glycolytic muscle compared to an oxidative muscle, indicating that intrinsic muscle oxidative capacity determines the response to cancer cachectic effects. (AU)

• Processo FAPESP: 16/50336-3 - Predicting survival in non-small-cell lung cancer: a link between cancer cachexia, cardiorespiratory fitness and cancer immune surveillance?
• Beneficiário: Patricia Chakur Brum
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/01478-0 - Mecanismos moleculares da caquexia do câncer: explorando o papel da COPS2
• Beneficiário: Christiano Robles Rodrigues Alves
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado Direto
• Processo FAPESP: 12/25240-1 - Efeitos do treinamento físico aeróbio intervalado em alta intensidade no músculo esquelético de ratos inoculados com o tumor Walker 256
• Beneficiário: Christiano Robles Rodrigues Alves
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Mestrado
• Processo FAPESP: 16/20187-6 - Caquexia em pacientes com carcinoma pulmonar de células não pequenas: influência da aptidão física sobre o prognóstico
• Beneficiário: Willian das Neves Silva
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 15/22814-5 - Câncer e coração: novos paradigmas de diagnóstico e tratamento
• Beneficiário: Carlos Eduardo Negrão
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 14/03016-8 - Caquexia do câncer: efeitos do treinamento físico aeróbio sobre o músculo esquelético em modelo animal
• Beneficiário: Christiano Robles Rodrigues Alves
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 12/02528-0 - Efeitos do treinamento físico aeróbio intervalado em alta intensidade no músculo esquelético de ratos inoculados com o tumor Walker 256
• Beneficiário: Christiano Robles Rodrigues Alves
• Modalidade de apoio: Bolsas no Brasil - Mestrado