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| Author(s): |
Barbara Moreira Crisol
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Limeira, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Aplicadas |
| Defense date: | 2023-03-13 |
| Examining board members: |
Eduardo Rochete Ropelle;
Adelino Sanchéz Ramos da Silva;
Fernando Moreira Simambuco;
Marcelo Alves Mori;
Ellen Cristini de Freitas
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| Advisor: | Eduardo Rochete Ropelle |
| Abstract | |
Long periods of high-volume and/or high-intensity physical training can experience the so-called overtraining syndrome, originating from several abnormalities in skeletal muscle, including low oxidative capacity and DNA damage. Poly [ADP-ribose] polymerases (PARPs) are proteins involved especially in DNA repair. On the other hand, the activation of PARPs generates an excessive consumption of NAD+, serving the mitochondrial activity. However, the effects of overtraining on the activation of PARPs in skeletal muscle are unknown. Here we combined bioinformatics and molecular analyzes to assess the effects of overtraining on PARP1, mitonuclear imbalance and UPRmt activation in the skeletal muscle of overtrained mice and humans. Overtraining leads to a muscle disorder, increasing PARP1 activity and impairing mitochondrial function. In addition, OT syndrome activated the integrated stress response (ISR) and UPRmt. These results were translated to humans, once volunteers exposed to excessive exercise training for one week presented a tendency to increase global parylation and HSP60 (UPRmt marker) protein contente in the skeletal muscle. Furthermore, PARP1 inhibtion protected against the performance impairment promoted by OT. Specially the pharmacological inhibition, using OLAPARIB, preserved mitochondrial function and reduced UPRmt activation, suggesting lower mitochondrial stress. Collectively, our results prove that OT can be considered a myopathy and we identify a potential target for prevention/treatment of this syndrome (AU) | |
| FAPESP's process: | 18/04192-5 - Evaluation of the Parilation and the Mitonuclear Imbalance and the UPRmt in the Skeletal Musculature of Mice in Overtraining. |
| Grantee: | Barbara Moreira Crisol |
| Support Opportunities: | Scholarships in Brazil - Doctorate |