Excessive exercise elicits poly (ADP-ribose) Polymerase-1 activation and global protein PARylation driving muscle dysfunction and performance impairment
Excessive exercise combined with inadequate recovery time may trigger fatigue, performance impairment, and ultimately the overtraining syndrome. The intramyocellular mechanisms involved in the overtraining syndrome remain only partially known. Here, we combined multi-omics analyses from isogenic BXD...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-06-01
|
| Series: | Molecular Metabolism |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877825000420 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849324072551317504 |
|---|---|
| author | Barbara M. Crisol Matheus B. Rocha Beatriz Franco Ana Paula Morelli Carlos K. Katashima Scylas J.A. Junior Fernanda S. Carneiro Renata R. Braga Rafael S. Brícola Graciana de Azambuja Raul Gobato Costa Andrea M. Esteves Marcelo A. Mori Maria C.G. Oliveira Dennys E. Cintra José R. Pauli Filip J. Larsen Adelino S.R. da Silva Eduardo R. Ropelle |
| author_facet | Barbara M. Crisol Matheus B. Rocha Beatriz Franco Ana Paula Morelli Carlos K. Katashima Scylas J.A. Junior Fernanda S. Carneiro Renata R. Braga Rafael S. Brícola Graciana de Azambuja Raul Gobato Costa Andrea M. Esteves Marcelo A. Mori Maria C.G. Oliveira Dennys E. Cintra José R. Pauli Filip J. Larsen Adelino S.R. da Silva Eduardo R. Ropelle |
| author_sort | Barbara M. Crisol |
| collection | DOAJ |
| description | Excessive exercise combined with inadequate recovery time may trigger fatigue, performance impairment, and ultimately the overtraining syndrome. The intramyocellular mechanisms involved in the overtraining syndrome remain only partially known. Here, we combined multi-omics analyses from isogenic BXD mouse strains with a mouse model of overtraining and excessive exercise protocol in mice and humans to evaluate the molecular mechanism involved in the performance impairment induced by excessive exercise. We identified that BXD mouse strains with elevated levels of Parp1 gene expression in the skeletal muscle displayed features like overtraining syndrome and abnormal muscle genetic signature. High PARP1 protein content and aberrant PARylation of proteins were detected in the skeletal muscle of overtrained, but not in trained mice. Overtraining syndrome reduced mitochondrial function promoted by exercise training, induced muscle hyperalgesia, reduced muscle fiber size and promoted a similar gene signature of myopathy and atrophy models. Short periods of excessive exercise also increased PARylation in the skeletal muscle of mice and healthy subjects. The pharmacological inhibition of PARP1, using Olaparib, and genetic Parp1 ablation, preserved muscle fiber morphology and protected against physical performance impairment and other symptoms of the overtraining syndrome in mice. In conclusion, PARP1 excessive activation is related to muscle abnormalities led by long or short periods of excessive exercise, and here we suggest that PARP1 is a potential target in the treatment and prevention of overtraining syndrome. |
| format | Article |
| id | doaj-art-79bd0ccb904d4e399ab423704dadbc7b |
| institution | Kabale University |
| issn | 2212-8778 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj-art-79bd0ccb904d4e399ab423704dadbc7b2025-08-20T03:48:50ZengElsevierMolecular Metabolism2212-87782025-06-019610213510.1016/j.molmet.2025.102135Excessive exercise elicits poly (ADP-ribose) Polymerase-1 activation and global protein PARylation driving muscle dysfunction and performance impairmentBarbara M. Crisol0Matheus B. Rocha1Beatriz Franco2Ana Paula Morelli3Carlos K. Katashima4Scylas J.A. Junior5Fernanda S. Carneiro6Renata R. Braga7Rafael S. Brícola8Graciana de Azambuja9Raul Gobato Costa10Andrea M. Esteves11Marcelo A. Mori12Maria C.G. Oliveira13Dennys E. Cintra14José R. Pauli15Filip J. Larsen16Adelino S.R. da Silva17Eduardo R. Ropelle18Laboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Limeira, SP, 13484-350, BrazilLaboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Limeira, SP, 13484-350, BrazilSchool of Applied Sciences, University of Campinas, Limeira, SP, BrazilLaboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Limeira, SP, 13484-350, BrazilLaboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Limeira, SP, 13484-350, BrazilLaboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Limeira, SP, 13484-350, BrazilLaboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Limeira, SP, 13484-350, BrazilLaboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Limeira, SP, 13484-350, BrazilLaboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Limeira, SP, 13484-350, BrazilSchool of Applied Sciences, University of Campinas, Limeira, SP, BrazilDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), BrazilSchool of Applied Sciences, University of Campinas, Limeira, SP, BrazilDepartment of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), BrazilSchool of Applied Sciences, University of Campinas, Limeira, SP, BrazilLaboratory of Nutritional Genomic, School of Applied Sciences, University of Campinas (UNICAMP), Limeira, SP, 13484-350, Brazil; Obesity and Comorbidities Research Center, University of Campinas (UNICAMP), BrazilLaboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Limeira, SP, 13484-350, Brazil; School of Applied Sciences, University of Campinas, Limeira, SP, Brazil; Obesity and Comorbidities Research Center, University of Campinas (UNICAMP), BrazilThe Swedish School of Sport and Health Sciences, GIH, Åstrand Laboratory, Department of Physiology, Nutrition and Biomechanics, Stockholm, 114 33, SwedenPostgraduate Program in Rehabilitation and Functional Performance, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto, SP, Brazil; School of Physical Education and Sport of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, BrazilLaboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Limeira, SP, 13484-350, Brazil; School of Applied Sciences, University of Campinas, Limeira, SP, Brazil; Obesity and Comorbidities Research Center, University of Campinas (UNICAMP), Brazil; Corresponding author. University of Campinas Laboratory of Molecular Biology of Exercise, 13484-350, Limeira, SP, Brazil.Excessive exercise combined with inadequate recovery time may trigger fatigue, performance impairment, and ultimately the overtraining syndrome. The intramyocellular mechanisms involved in the overtraining syndrome remain only partially known. Here, we combined multi-omics analyses from isogenic BXD mouse strains with a mouse model of overtraining and excessive exercise protocol in mice and humans to evaluate the molecular mechanism involved in the performance impairment induced by excessive exercise. We identified that BXD mouse strains with elevated levels of Parp1 gene expression in the skeletal muscle displayed features like overtraining syndrome and abnormal muscle genetic signature. High PARP1 protein content and aberrant PARylation of proteins were detected in the skeletal muscle of overtrained, but not in trained mice. Overtraining syndrome reduced mitochondrial function promoted by exercise training, induced muscle hyperalgesia, reduced muscle fiber size and promoted a similar gene signature of myopathy and atrophy models. Short periods of excessive exercise also increased PARylation in the skeletal muscle of mice and healthy subjects. The pharmacological inhibition of PARP1, using Olaparib, and genetic Parp1 ablation, preserved muscle fiber morphology and protected against physical performance impairment and other symptoms of the overtraining syndrome in mice. In conclusion, PARP1 excessive activation is related to muscle abnormalities led by long or short periods of excessive exercise, and here we suggest that PARP1 is a potential target in the treatment and prevention of overtraining syndrome.http://www.sciencedirect.com/science/article/pii/S2212877825000420ExerciseMusclePARP1overtraining |
| spellingShingle | Barbara M. Crisol Matheus B. Rocha Beatriz Franco Ana Paula Morelli Carlos K. Katashima Scylas J.A. Junior Fernanda S. Carneiro Renata R. Braga Rafael S. Brícola Graciana de Azambuja Raul Gobato Costa Andrea M. Esteves Marcelo A. Mori Maria C.G. Oliveira Dennys E. Cintra José R. Pauli Filip J. Larsen Adelino S.R. da Silva Eduardo R. Ropelle Excessive exercise elicits poly (ADP-ribose) Polymerase-1 activation and global protein PARylation driving muscle dysfunction and performance impairment Molecular Metabolism Exercise Muscle PARP1 overtraining |
| title | Excessive exercise elicits poly (ADP-ribose) Polymerase-1 activation and global protein PARylation driving muscle dysfunction and performance impairment |
| title_full | Excessive exercise elicits poly (ADP-ribose) Polymerase-1 activation and global protein PARylation driving muscle dysfunction and performance impairment |
| title_fullStr | Excessive exercise elicits poly (ADP-ribose) Polymerase-1 activation and global protein PARylation driving muscle dysfunction and performance impairment |
| title_full_unstemmed | Excessive exercise elicits poly (ADP-ribose) Polymerase-1 activation and global protein PARylation driving muscle dysfunction and performance impairment |
| title_short | Excessive exercise elicits poly (ADP-ribose) Polymerase-1 activation and global protein PARylation driving muscle dysfunction and performance impairment |
| title_sort | excessive exercise elicits poly adp ribose polymerase 1 activation and global protein parylation driving muscle dysfunction and performance impairment |
| topic | Exercise Muscle PARP1 overtraining |
| url | http://www.sciencedirect.com/science/article/pii/S2212877825000420 |
| work_keys_str_mv | AT barbaramcrisol excessiveexerciseelicitspolyadpribosepolymerase1activationandglobalproteinparylationdrivingmuscledysfunctionandperformanceimpairment AT matheusbrocha excessiveexerciseelicitspolyadpribosepolymerase1activationandglobalproteinparylationdrivingmuscledysfunctionandperformanceimpairment AT beatrizfranco excessiveexerciseelicitspolyadpribosepolymerase1activationandglobalproteinparylationdrivingmuscledysfunctionandperformanceimpairment AT anapaulamorelli excessiveexerciseelicitspolyadpribosepolymerase1activationandglobalproteinparylationdrivingmuscledysfunctionandperformanceimpairment AT carloskkatashima excessiveexerciseelicitspolyadpribosepolymerase1activationandglobalproteinparylationdrivingmuscledysfunctionandperformanceimpairment AT scylasjajunior excessiveexerciseelicitspolyadpribosepolymerase1activationandglobalproteinparylationdrivingmuscledysfunctionandperformanceimpairment AT fernandascarneiro excessiveexerciseelicitspolyadpribosepolymerase1activationandglobalproteinparylationdrivingmuscledysfunctionandperformanceimpairment AT renatarbraga excessiveexerciseelicitspolyadpribosepolymerase1activationandglobalproteinparylationdrivingmuscledysfunctionandperformanceimpairment AT rafaelsbricola excessiveexerciseelicitspolyadpribosepolymerase1activationandglobalproteinparylationdrivingmuscledysfunctionandperformanceimpairment AT gracianadeazambuja excessiveexerciseelicitspolyadpribosepolymerase1activationandglobalproteinparylationdrivingmuscledysfunctionandperformanceimpairment AT raulgobatocosta excessiveexerciseelicitspolyadpribosepolymerase1activationandglobalproteinparylationdrivingmuscledysfunctionandperformanceimpairment AT andreamesteves excessiveexerciseelicitspolyadpribosepolymerase1activationandglobalproteinparylationdrivingmuscledysfunctionandperformanceimpairment AT marceloamori excessiveexerciseelicitspolyadpribosepolymerase1activationandglobalproteinparylationdrivingmuscledysfunctionandperformanceimpairment AT mariacgoliveira excessiveexerciseelicitspolyadpribosepolymerase1activationandglobalproteinparylationdrivingmuscledysfunctionandperformanceimpairment AT dennysecintra excessiveexerciseelicitspolyadpribosepolymerase1activationandglobalproteinparylationdrivingmuscledysfunctionandperformanceimpairment AT joserpauli excessiveexerciseelicitspolyadpribosepolymerase1activationandglobalproteinparylationdrivingmuscledysfunctionandperformanceimpairment AT filipjlarsen excessiveexerciseelicitspolyadpribosepolymerase1activationandglobalproteinparylationdrivingmuscledysfunctionandperformanceimpairment AT adelinosrdasilva excessiveexerciseelicitspolyadpribosepolymerase1activationandglobalproteinparylationdrivingmuscledysfunctionandperformanceimpairment AT eduardorropelle excessiveexerciseelicitspolyadpribosepolymerase1activationandglobalproteinparylationdrivingmuscledysfunctionandperformanceimpairment |