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

Author(s):Show less -

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]

Affiliation

^[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

• Document type: Journal article
• Source: FASEB JOURNAL; v. 35, n. 7 JUL 2021.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 16/50336-3 - Predicting survival in non-small-cell lung cancer: a link between cancer cachexia, cardiorespiratory fitness and cancer immune surveillance?
• Grantee: Patricia Chakur Brum
• Support type: Regular Research Grants
• FAPESP's process: 16/01478-0 - Molecular mechanisms underlying cancer cachexia: exploring the role of COPS2
• Grantee: Christiano Robles Rodrigues Alves
• Support type: Scholarships abroad - Research Internship - Doctorate (Direct)
• FAPESP's process: 12/25240-1 - Effects of high-intensity interval training on skeletal muscle of Walker 256 tumor-bearing rats
• Grantee: Christiano Robles Rodrigues Alves
• Support type: Scholarships abroad - Research Internship - Master's degree
• FAPESP's process: 16/20187-6 - Caquexia in non-small cell lung cancer patient: physical fitness influence on prognosis
• Grantee: Willian das Neves Silva
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 15/22814-5 - Cancer and heart: new paradigms of diagnosis and treatment
• Grantee: Carlos Eduardo Negrão
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 14/03016-8 - Cancer cachexia: effects of aerobic physical training on skeletal muscle in animal model
• Grantee: Christiano Robles Rodrigues Alves
• Support type: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 12/02528-0 - Effects of high-intensity physical training on skeletal muscle of Walker 256 tumor-bearing rats
• Grantee: Christiano Robles Rodrigues Alves
• Support type: Scholarships in Brazil - Master