Compartmentalized muscle redox signals controlling exercise metabolism – Current state, future challenges

Henríquez‐Olguín, Carlos; Meneses‐Valdés, Roberto; Jensen, Thomas E.

doi:10.1016/j.redox.2020.101473

Cited by 36 publications

(33 citation statements)

References 95 publications

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“…A potential source of the necessary H 2 O 2 , therefore, continues to operate. Moreover, the vast majority of redox research in an exercise setting recapitulates linear moderate/high intensity work and it could be argued the active recovery employed within this study creates a switch in ATP demand, potentially increasing mitochondrial O 2 ·-/H 2 O 2 production [ 63 ]; this highlights our limited understanding of exercising human in vivo mitochondrial redox dynamics. That is, cyclic fluxes in work done may induce oscillatory mitochondrial superoxide behaviour (i.e., troughs during the bout and peaks during the rest).…”

Section: Discussionmentioning

confidence: 99%

The mitochondria-targeted antioxidant MitoQ, attenuates exercise-induced mitochondrial DNA damage

et al. 2020

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High-intensity exercise damages mitochondrial DNA (mtDNA) in skeletal muscle. Whether MitoQ - a redox active mitochondrial targeted quinone - can reduce exercise-induced mtDNA damage is unknown. In a double-blind, randomized, placebo-controlled design, twenty-four healthy male participants consisting of two groups (placebo; n = 12, MitoQ; n = 12) performed an exercise trial of 4 x 4-min bouts at 90–95% of heart rate max. Participants completed an acute (20 mg MitoQ or placebo 1-h pre-exercise) and chronic (21 days of supplementation) phase. Blood and skeletal muscle were sampled immediately pre- and post-exercise and analysed for nuclear and mtDNA damage, lipid hydroperoxides, lipid soluble antioxidants, and the ascorbyl free radical. Exercise significantly increased nuclear and mtDNA damage across lymphocytes and muscle ( P < 0.05), which was accompanied with changes in lipid hydroperoxides, ascorbyl free radical, and α-tocopherol ( P < 0.05). Acute MitoQ treatment failed to impact any biomarker likely due to insufficient initial bioavailability. However, chronic MitoQ treatment attenuated nuclear ( P < 0.05) and mtDNA damage in lymphocytes and muscle tissue ( P < 0.05). Our work is the first to show a protective effect of chronic MitoQ supplementation on the mitochondrial and nuclear genomes in lymphocytes and human muscle tissue following exercise, which is important for genome stability.

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Section: Discussionmentioning

confidence: 99%

The mitochondria-targeted antioxidant MitoQ, attenuates exercise-induced mitochondrial DNA damage

et al. 2020

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“…SOD1 is located in the cytoplasm, nucleus and outer mitochondrial membrane, while Catalase is a predominantly extramitochondrial protein, but also found in the mitochondrial matrix [ 67 , 70 ]. SOD1 was slightly increased during exercise in hypoxia, facilitating the dismutation of superoxide generated by extramitochondrial oxidases [ 71 ]. This response concurs with the observed increased RONS production during high-intensity exercise in hypoxia [ 3 ], which has a significant cytoplasmatic component [ 66 , 71 ].…”

Section: Discussionmentioning

confidence: 99%

“…SOD1 was slightly increased during exercise in hypoxia, facilitating the dismutation of superoxide generated by extramitochondrial oxidases [ 71 ]. This response concurs with the observed increased RONS production during high-intensity exercise in hypoxia [ 3 ], which has a significant cytoplasmatic component [ 66 , 71 ]. In the presence of higher levels of SOD1, the production of H 2 O 2 is likely increased during exercise in severe hypoxia, requiring a higher amount of Catalase to avoid unchecked oxidative damage.…”

Section: Discussionmentioning

confidence: 99%

“…The latter was accompanied by the expected, although non-statistically significant, changes in the protein expression of Ser 40 Nrf2, Nrf2 total, Nrf2 total/Keap1, and Keap1. The fact that the antioxidant enzymes increased in response to exercise and ischaemia are located mostly outside the mitochondria is compatible with a predominant extramitochondrial production of RONS during exercise [ 71 ], which may be even more marked during exercise in hypoxia and ischaemia.…”

Section: Discussionmentioning

confidence: 99%

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Regulation of Nrf2/Keap1 signalling in human skeletal muscle during exercise to exhaustion in normoxia, severe acute hypoxia and post-exercise ischaemia: Influence of metabolite accumulation and oxygenation

et al. 2020

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The Nrf2 transcription factor is induced by reactive oxygen and nitrogen species and is necessary for the adaptive response to exercise in mice. It remains unknown whether Nrf2 signalling is activated by exercise in human skeletal muscle. Here we show that Nrf2 signalling is activated by exercise to exhaustion with similar responses in normoxia (P I O 2 : 143 mmHg) and severe acute hypoxia (P I O 2 : 73 mmHg). CaMKII and AMPKα phosphorylation were similarly induced in both conditions. Enhanced Nrf2 signalling was achieved by raising Nrf2 total protein and Ser 40 Nrf2 phosphorylation, accompanied by a reduction of Keap1. Keap1 protein degradation is facilitated by the phosphorylation of p62/SQSTM1 at Ser 349 by AMPK, which targets Keap1 for autophagic degradation. Consequently, the Nrf2-to-Keap1 ratio was markedly elevated and closely associated with a 2-3-fold increase in Catalase protein. No relationship was observed between Nrf2 signalling and SOD1 and SOD2 protein levels. Application of ischaemia immediately at the end of exercise maintained these changes, which were reverted within 1 min of recovery with free circulation. While SOD2 did not change significantly during either exercise or ischaemia, SOD1 protein expression was marginally downregulated and upregulated during exercise in normoxia and hypoxia, respectively. We conclude that Nrf2/Keap1/Catalase pathway is rapidly regulated during exercise and recovery in human skeletal muscle. Catalase emerges as an essential antioxidant enzyme acutely upregulated during exercise and ischaemia. Post-exercise ischaemia maintains Nrf2 signalling at the level reached at exhaustion and can be used to avoid early post-exercise recovery, which is O 2 -dependent.

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“…Second, Click PEGylation could be used to assess exercise-induced redox signaling [177][178][179][180][181][182][183][184]. A recent comprehensive review [185] concluded that redox signaling is central to exercise responses and adaptations (e.g., mitochondrial biogenesis [186,187]).…”

Section: Opportunities: How To Use Click Pegylation To Advance Knowlementioning

confidence: 99%

Immunological Techniques to Assess Protein Thiol Redox State: Opportunities, Challenges and Solutions

Cobley

Husi

2020

Antioxidants

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To understand oxidative stress, antioxidant defense, and redox signaling in health and disease it is essential to assess protein thiol redox state. Protein thiol redox state is seldom assessed immunologically because of the inability to distinguish reduced and reversibly oxidized thiols by Western blotting. An underappreciated opportunity exists to use Click PEGylation to realize the transformative power of simple, time and cost-efficient immunological techniques. Click PEGylation harnesses selective, bio-orthogonal Click chemistry to separate reduced and reversibly oxidized thiols by selectively ligating a low molecular weight polyethylene glycol moiety to the redox state of interest. The resultant ability to disambiguate reduced and reversibly oxidized species by Western blotting enables Click PEGylation to assess protein thiol redox state. In the present review, to enable investigators to effectively harness immunological techniques to assess protein thiol redox state we critique the chemistry, promise and challenges of Click PEGylation.

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Compartmentalized muscle redox signals controlling exercise metabolism – Current state, future challenges

Cited by 36 publications

References 95 publications

The mitochondria-targeted antioxidant MitoQ, attenuates exercise-induced mitochondrial DNA damage

The mitochondria-targeted antioxidant MitoQ, attenuates exercise-induced mitochondrial DNA damage

Regulation of Nrf2/Keap1 signalling in human skeletal muscle during exercise to exhaustion in normoxia, severe acute hypoxia and post-exercise ischaemia: Influence of metabolite accumulation and oxygenation

Immunological Techniques to Assess Protein Thiol Redox State: Opportunities, Challenges and Solutions

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