Evaluation of the Parilation and the Mitonuclear Imbalance and the UPRmt in the Skeletal Musculature of Mice in Overtraining.

• Grant number: 18/04192-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2018
• End date: March 31, 2023
• Field of knowledge: Biological Sciences - Physiology - Physiology of Effort
• Principal Investigator: Eduardo Rochete Ropelle
• Grantee: Barbara Moreira Crisol
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
• Associated scholarship(s): 19/22512-0 - Effects of calorie restriction and exercise in the skeletal muscle protein aggregration, BE.EP.DR

Abstract

Long periods of high volume physical training and / or intensity may trigger the so-called overtraining syndrome in athletes. The loss of the body's ability to recover between training sessions can contribute significantly to the development of overtainment.During the overtraining process, skeletal musculature has several abnormalities, including damage to various cellular structures, including DNA, increased oxidative stress and reduced oxidative capacity and energy production, leading athletes to significant performance decrease. Poly [ADP-ribose] polymerases (PARPs) are proteins involved especially in DNA repair. When activated in response to DNA damage, PARPs induce the parulation of several proteins involved in DNA repair. However, the activation of the PARPs generates an excessive consumption of NAD +, generating several deleterious effects for the eukaryotic cells, mainly with respect to energy production.Recent studies have shown that PARP inhibitors generate abundance of NAD + levels inducing potent signals to mitochondria, promoting increased oxidative capacity and increased mitochondrial biogenesis, among which the following stand out: "mitonuclear imbalance" induction and activation of UPRmt, of the English mitochondrial unfolded protein response. Mitunuclear imbalance" and UPRmt are highly conserved mechanisms among species and essential for reestablishing proteasy within mitochondria, allowing the cells to survive under stress. In this scenario, we hypothesized that muscle damage generated by excessive physical training could stimulate the activation of PARPs, reducing the availability of NAD + as well as the ability of muscle cells to respond to stress through "mitonuclear imbalance" and activation of UPRmt in the skeletal muscles. Thus, the aim of the current project will be to evaluate the activation of PARP1, "mitonuclear imbalance" and UPRmt in the skeletal muscle of overtreated mice.

Scientific publications

(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)

KATASHIMA, CARLOS KIYOSHI; MICHELETTI, THAYANA DE OLIVEIRA; BRAGA, RENATA ROSSETO; GASPAR, RODRIGO STELLZER; GOEMINNE, LUDGER J. E.; MOURA-ASSIS, ALEXANDRE; CRISOL, BARBARA MOREIRA; BRICOLA, RAFAEL S.; SILVA, VAGNER RAMON R.; RAMOS, CAMILA DE OLIVEIRA; et al. Evidence for a neuromuscular circuit involving hypothalamic interleukin-6 in the control of skeletal muscle metabolism. SCIENCE ADVANCES, v. 8, n. 30, p. 14-pg., 2022-07-29. (12/23006-1, 19/21709-4, 13/26053-3, 18/04192-5)

Academic Publications

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

CRISOL, Barbara Moreira. Evaluation of parylation, mitonuclear imbalance, and UPRmt in the skeletal muscle of mice in overtraining. 2023. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Aplicadas Limeira, SP.