Overexpression of manganese superoxide dismutase mitigates ACL injury-induced muscle atrophy, weakness and oxidative damage.

Autor: Latham CM; Center for Muscle Biology, University of Kentucky, Lexington, KY, USA; Department of Athletic Training and Clinical Nutrition, College of Health Sciences, University of Kentucky, Lexington, KY, USA., Balawender PJ; Center for Muscle Biology, University of Kentucky, Lexington, KY, USA., Thomas NT; Center for Muscle Biology, University of Kentucky, Lexington, KY, USA; Department of Athletic Training and Clinical Nutrition, College of Health Sciences, University of Kentucky, Lexington, KY, USA., Keeble AR; Center for Muscle Biology, University of Kentucky, Lexington, KY, USA; Department of Athletic Training and Clinical Nutrition, College of Health Sciences, University of Kentucky, Lexington, KY, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY, USA., Brightwell CR; Center for Muscle Biology, University of Kentucky, Lexington, KY, USA; Department of Athletic Training and Clinical Nutrition, College of Health Sciences, University of Kentucky, Lexington, KY, USA., Ismaeel A; Center for Muscle Biology, University of Kentucky, Lexington, KY, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY, USA., Wen Y; Center for Muscle Biology, University of Kentucky, Lexington, KY, USA; Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY, USA; Division of Biomedical Informatics, Department of Internal Medicine, College of Medicine, University of Kentucky, Lexington, KY, USA., Fry JL; Center for Muscle Biology, University of Kentucky, Lexington, KY, USA; Department of Athletic Training and Clinical Nutrition, College of Health Sciences, University of Kentucky, Lexington, KY, USA., Sullivan PG; Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY, USA., Johnson DL; Department of Orthopaedic Surgery and Sports Medicine, College of Medicine, University of Kentucky, Lexington, KY, USA., Noehren B; Center for Muscle Biology, University of Kentucky, Lexington, KY, USA; Department of Orthopaedic Surgery and Sports Medicine, College of Medicine, University of Kentucky, Lexington, KY, USA; Department of Physical Therapy, College of Health Sciences, University of Kentucky, Lexington, KY, USA., Owen AM; Center for Muscle Biology, University of Kentucky, Lexington, KY, USA; Department of Athletic Training and Clinical Nutrition, College of Health Sciences, University of Kentucky, Lexington, KY, USA. Electronic address: allison.owen@uky.edu., Fry CS; Center for Muscle Biology, University of Kentucky, Lexington, KY, USA; Department of Athletic Training and Clinical Nutrition, College of Health Sciences, University of Kentucky, Lexington, KY, USA. Electronic address: christopher.fry@uky.edu.
Jazyk: angličtina
Zdroj: Free radical biology & medicine [Free Radic Biol Med] 2024 Feb 20; Vol. 212, pp. 191-198. Date of Electronic Publication: 2023 Dec 26.
DOI: 10.1016/j.freeradbiomed.2023.12.037
Abstrakt: Oxidative stress has been implicated in the etiology of skeletal muscle weakness following joint injury. We investigated longitudinal patient muscle samples following knee injury (anterior cruciate ligament tear). Following injury, transcriptomic analysis revealed downregulation of mitochondrial metabolism-related gene networks, which were supported by reduced mitochondrial respiratory flux rates. Additionally, enrichment of reactive oxygen species (ROS)-related pathways were upregulated in muscle following knee injury, and further investigation unveiled marked oxidative damage in a progressive manner following injury and surgical reconstruction. We then investigated whether antioxidant protection is effective in preventing muscle atrophy and weakness after knee injury in mice that overexpress Mn-superoxide dismutase (MnSOD +/- ). MnSOD +/- mice showed attenuated oxidative damage, atrophy, and muscle weakness compared to wild type littermate controls following ACL transection surgery. Taken together, our results indicate that ROS-related damage is a causative mechanism of muscle dysfunction after knee injury, and that mitochondrial antioxidant protection may hold promise as a therapeutic target to prevent weakness and development of disability.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Christopher Fry reports financial support was provided by University of Kentucky. Christopher Fry reports a relationship with University of Kentucky that includes: funding grants.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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