Effects of intermittent exposure to hypobaric hypoxia and cold on skeletal muscle regeneration: Mitochondrial dynamics, protein oxidation and turnover

• Published in: Free radical biology & medicine 2024-11, Vol.225, p.286-295
• Main Authors: Sánchez-Nuño, Sergio, Santocildes, Garoa, Rebull, Josep, Bardallo, Raquel G., Girabent-Farrés, Montserrat, Viscor, Ginés, Carbonell, Teresa, Torrella, Joan Ramon
• Format: Article
• Language: English
• Subjects: Animals; Cold Temperature; Electron transport chain; Hypoxia - metabolism; Intermittent cold exposure; Intermittent hypobaric hypoxia; Male; Mitochondria, Muscle - metabolism; Mitochondrial Dynamics; Muscle, Skeletal - metabolism; Nitric Oxide Synthase Type III - genetics; Nitric Oxide Synthase Type III - metabolism; Oxidation-Reduction; Proteasome Endopeptidase Complex - metabolism; Protein oxidation; Rats; Rats, Wistar; Redox; Regeneration
• ISSN: 0891-5849; 1873-4596; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2024.09.032

Muscle injuries and the subsequent regeneration events compromise muscle homeostasis at morphological, functional and molecular levels. Among the molecular alterations, those derived from the mitochondrial function are especially relevant. We analysed the mitochondrial dynamics, the redox balance, the protein oxidation and the main protein repairing mechanisms after 9 days of injury in the rat gastrocnemius muscle. During the recovery rats were exposed to intermittent cold exposure (ICE), intermittent hypobaric hypoxia (IHH), and both simultaneous combined stimuli. Non-injured contralateral legs were also analysed to evaluate the specific effects of the three environmental exposures. Our results showed that ICE enhanced mitochondrial adaptation by improving the electron transport chain efficiency during muscle recovery, decreased the expression of regulatory subunit of proteasome and accumulated oxidized proteins. Exposure to IHH did not show mitochondrial compensation or increased protein turnover mechanisms; however, no accumulation of oxidized proteins was observed. Both ICE and IHH, when applied separately, elicited an increased expression of eNOS, which could have played an important role in accelerating muscle recovery. The combined effect of ICE and IHH led to a complex response that could potentially impede optimal mitochondrial function and enhanced the accumulation of protein oxidation. These findings underscore the nuanced role of environmental stressors in the muscle healing process and their implications for optimizing recovery strategies. [Display omitted] •9 days of ICE decrease PARKIN (mitophagy) expression and increase ETC expression.•IHH exposure reduced the expression of complex III (ROS production) of the ETC.•Combined ICE and IHH exposure decreased ETC complexes expression in injured muscle.•ICE and IHH increase ubiquitination of higher molecular weight proteins.•Higher expression of eNOS after ICE and IHH increased vasodilation to injured muscle.