Emerging role of rev-erb-alpha in molecular adaptations to different physical exercise models

• Grant number: 17/12765-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2018
• End date: February 28, 2022
• Field of knowledge: Health Sciences - Physical Education
• Principal Investigator: Adelino Sanchez Ramos da Silva
• Grantee: Alisson Luiz da Rocha
• Host Institution: Escola de Educação Física e Esporte de Ribeirão Preto (EEFERP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Recently, the nuclear receptor rev-erb-alpha has been considered to play an important role in the skeletal muscle oxidative capacity adaptation, modulating the AMP-activated Protein Kinase (AMPK) signaling pathway. Classically, endurance physical exercise is able to activate this signaling pathway, but the effects of this and other physical exercise models (i.e., resistance and exhaustive) on rev-erb-alpha remain unknown. Besides the transcriptional regulation of this signaling pathway, rev-erb-alpha is also capable to regulate negatively the autophagy pathway in skeletal muscle and the dopamine biosynthesis in hippocampus. It is suggested in the literature that dopamine, together with serotonin, play a role in Central Nervous System (CNS) fatigue development. Briefly, rev-erb-alpha is candidate to modulate the molecular adaptations that regulate physical performance, CNS fatigue and autophagy. Thus, the main aim of the present project is to investigate the role of rev-erb-alpha in the molecular adaptations that regulate physical performance, CNS fatigue and autophagy after different exercise models. Mice will be divided into 5 groups: control (CT, sedentary); endurance I (END1, submitted to aerobic physical exercise protocol 1); endurance II (END2, submitted to aerobic physical exercise protocol 2); resistance (RES, submitted to strength physical exercise protocol) and exhaustive (OT; submitted to downhill overtraining protocol). As a translational characteristic, we will compare the messenger RNA of rev-erb-alpha and autophagic genes among sedentary and trained individuals. The following methodologies will be used: immunoblotting, real-time Polymerase Chain Reaction (qPCR), immunofluorescence and HPLC. According to the statistical data distribution, parametric or nonparametric tests will be used to compare the investigated parameters between the experimental groups. The level of significance of p < 0.05 will be adopted. (AU)

Scientific publications

(12)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PINTO, ANA P.; DA ROCHA, ALISSON L.; CABRERA, ELISA M. B.; MARAFON, BRUNO B.; KOHAMA, EIKE B.; ROVINA, RAFAEL L.; SIMABUCO, FERNANDO M.; BUENO JUNIOR, CARLOS R.; DE MOURA, LEANDRO P.; PAULI, JOSE R.; et al. Role of interleukin-6 in inhibiting hepatic autophagy markers in exercised mice. CYTOKINE, v. 130, JUN 2020. (17/09038-1, 18/14818-9, 18/12519-4, 17/19869-8, 17/12765-2, 19/10875-0)

DA ROCHA, ALISSON L.; PINTO, ANA P.; KOHAMA, EIKE B.; PAULI, JOSE R.; DE MOURA, LEANDRO P.; CINTRA, DENNYS E.; ROPELLE, EDUARDO R.; DA SILVA, ADELINO S. R.. The proinflammatory effects of chronic excessive exercise. CYTOKINE, v. 119, p. 57-61, JUL 2019. (12/23258-0, 13/19985-7, 17/12765-2, 14/25459-9, 10/08239-4, 13/22737-5, 15/08013-0, 13/20591-3, 17/19869-8, 11/02652-0, 17/09038-1)

PINTO, ANA P.; DA ROCHA, ALISSON L.; TEIXEIRA, GIOVANA R.; ROVINA, RAFAEL L.; VERAS, ALLICE S. C.; FRANTZ, FABIANI; PAULI, JOSE R.; DE MOURA, LEANDRO P.; CINTRA, DENNYS E.; ROPELLE, EDUARDO R.; et al. Rapamycin did not prevent the excessive exercise-induced hepatic fat accumulation. Life Sciences, v. 306, p. 12-pg., 2022-07-15. (17/12765-2, 19/17058-8, 17/09038-1, 19/00137-2, 19/15428-2, 17/19869-8)

PINTO, ANA P.; DA ROCHA, ALISSON L.; MARAFON, BRUNO B.; ROVINA, RAFAEL L.; MUNOZ, VITOR R.; DA SILVA, LILIAN E. C. M.; PAULI, JOSE R.; DE MOURA, LEANDRO P.; CINTRA, DENNYS E.; ROPELLE, EDUARDO R.; et al. Impact of Different Physical Exercises on the Expression of Autophagy Markers in Mice. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 22, n. 5, MAR 2021. (17/09038-1, 17/19869-8, 19/10875-0, 17/12765-2)

ROVINA, RAFAEL L.; PINTO, ANA P.; MUNOZ, VITOR R.; DA ROCHA, ALISSON L.; REBELO, MACARIO A.; TEIXEIRA, GIOVANA R.; TAVARES, MARIA EDUARDA A.; PAULI, JOSE R.; DE MOURA, LEANDRO P.; CINTRA, DENNYS E.; et al. Genetic deletion of IL-6 increases CK-MB, a classic cardiac damage marker, and decreases UPRmt genes after exhaustive exercise. Cell Biochemistry and Function, v. 40, n. 4, p. 10-pg., 2022-04-12. (17/19869-8, 17/09038-1, 19/17058-8, 17/12765-2)

ROVINA, RAFAEL L.; DA ROCHA, ALISSON L.; MARAFON, BRUNO B.; PAULI, JOSE R.; DE MOURA, LEANDRO P.; CINTRA, DENNYS E.; ROPELLE, EDUARDO R.; DA SILVA, ADELINO S. R.. One Bout of Aerobic Exercise Can Enhance the Expression of Nr1d1 in Oxidative Skeletal Muscle Samples. FRONTIERS IN PHYSIOLOGY, v. 12, FEB 1 2021. (17/12765-2, 18/12519-4, 17/09038-1)

DE VICENTE, LARISSA G.; PINTO, ANA P.; MUNOZ, VITOR R.; ROVINA, RAFAEL L.; DA ROCHA, ALISSON L.; GASPAR, RAFAEL C.; DA SILVA, LILIAN E. C. M.; SIMABUCO, FERNANDO M.; FRANTZ, FABIANI G.; PAULI, JOSE R.; et al. Tlr4 participates in the responses of markers of apoptosis, inflammation, and ER stress to different acute exercise intensities in mice hearts. Life Sciences, v. 240, JAN 1 2020. (12/13558-7, 17/09038-1, 18/14818-9, 18/12519-4, 17/19869-8, 17/12765-2)

PINTO, ANA P.; MUNOZ, VITOR R.; DA ROCHA, ALISSON L.; ROVINA, RAFAEL L.; FERRARI, GUSTAVO D.; ALBERICI, LUCIANE C.; SIMABUCO, FERNANDO M.; TEIXEIRA, GIOVANA R.; PAULI, JOSE R.; DE MOURA, LEANDRO P.; et al. IL-6 deletion decreased REV-ERB alpha protein and influenced autophagy and mitochondrial markers in the skeletal muscle after acute exercise. FRONTIERS IN IMMUNOLOGY, v. 13, p. 13-pg., 2022-10-13. (21/06291-3, 21/08693-1, 19/11820-5, 17/12765-2, 19/21709-4, 21/08692-5, 20/13443-1, 18/14818-9)

DA ROCHA, ALISSON L.; PINTO, ANA P.; BEDO, BRUNO L. S.; MORAIS, GUSTAVO P.; OLIVEIRA, LUCIANA C.; CAROLINO, RUITHER O. G.; PAULI, JOSE R.; SIMABUCO, FERNANDO M.; DE MOURA, LEANDRO P.; ROPELLE, EDUARDO R.; et al. Exercise alters the circadian rhythm of REV-ERB-alpha and downregulates autophagy-related genes in peripheral and central tissues. SCIENTIFIC REPORTS, v. 12, n. 1, p. 13-pg., 2022-11-21. (21/08693-1, 19/17532-1, 17/25492-4, 19/11820-5, 17/19869-8, 17/12765-2)

DA ROCHA, ALISSON L.; PINTO, ANA P.; MORAIS, GUSTAVO P.; MARAFON, BRUNO B.; ROVINA, RAFAEL L.; VERAS, ALLICE S. C.; TEIXEIRA, GIOVANA R.; PAULI, JOSE R.; DE MOURA, LEANDRO P.; CINTRA, DENNYS E.; et al. Moderate, but Not Excessive, Training Attenuates Autophagy Machinery in Metabolic Tissues. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 21, n. 22, NOV 2020. (17/17646-1, 17/19869-8, 19/00855-2, 17/09038-1, 17/12765-2)

NOGUEIRA, JONATAS E.; AMORIM, MATEUS R.; PINTO, ANA P.; DA ROCHA, ALISSON L.; DA SILVA, ADELINO S. R.; BRANCO, LUIZ G. S.. Molecular hydrogen downregulates acute exhaustive exercise-induced skeletal muscle damage. Canadian Journal of Physiology and Pharmacology, v. 99, n. 8, p. 812-820, AUG 2021. (17/09878-0, 16/17681-9, 17/19869-8, 17/12765-2)

PINTO, ANA P.; DA ROCHA, ALISSON L.; KOHAMA, EIKE B.; GASPAR, RAFAEL C.; SIMABUCO, FERNANDO M.; FRANTZ, FABIANI G.; DE MOURA, LEANDRO P.; PAULI, JOSE R.; CINTRA, DENNYS E.; ROPELLE, EDUARDO R.; et al. Exhaustive acute exercise-induced ER stress is attenuated in IL-6-knockout mice. Journal of Endocrinology, v. 240, n. 2, p. 181-193, FEB 2019. (17/19869-8, 12/13558-7, 17/12765-2, 17/09038-1)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

ROCHA, Alisson Luiz da. Emerging role of rev-erb-α in molecular adaptations to different physical exercise models. 2022. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.