New Functions of Reactive Oxygen Species in Skeletal Muscle: From Regulatory Activities to Pathophysiological Conditions

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "ROS, RNS and RSS".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 13714

Special Issue Editor


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Guest Editor
Institute of Physiology and Pathophysiology, Physiology of School of Medicine, Heidelberg University Hospital, 69120 Heidelberg, Germany
Interests: skeletal muscle; cardiac muscle; calcium transient; nitric oxide; oxidative stress; Duchenne muscular dystrophy; skeletal muscle tissue engineering

Special Issue Information

Dear Colleagues,

Skeletal muscles have interesting and diversified roles in the body, starting from the most fundamental such as movement up to the most complex such as metabolism and regulation of temperature. Each general muscle function is well defined and regulated by specific signaling pathways, such as muscle growth and development with PI3K-Akt-mTOR; muscle contraction with excitation–contraction coupling, the neuro-muscular junction, the L-type calcium channel, the ryanodine receptor, and sarco-endoplasmic calcium ATPase; exercise with nuclear factor kappa B and peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha; and metabolism with glucose. These signaling pathways are modulated by reactive oxygen species (ROS) and reactive nitrogen species (RNS) and, despite the great advancements achieved in recent decades, ROS and RNS functions are mainly associated with several altered muscle functions during pathological conditions.

Therefore, in this Special Issue of Antioxidants, the aim is to collect impressive and outstanding original manuscripts or high-quality reviews about the state-of-the-art functions of ROS and RNS in skeletal muscles under normal and pathophysiological conditions.

Dr. Matias Mosqueira
Guest Editor

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Keywords

  • skeletal muscle
  • reactive oxygen species
  • reactive nitrogen species
  • EC coupling
  • metabolism
  • nitric oxide
  • nitric oxide synthase
  • exercise
  • concentric contraction
  • eccentric contraction

Published Papers (5 papers)

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Research

14 pages, 1275 KiB  
Article
Circulating Nrf2, Glutathione, and Malondialdehyde Correlate with Disease Severity in Duchenne Muscular Dystrophy
by Tomas Almeida-Becerril, Maricela Rodríguez-Cruz, Judith Villa-Morales, Christian Ricardo Sánchez-Mendoza and Jose Emilio Galeazzi-Aguilar
Antioxidants 2023, 12(4), 871; https://doi.org/10.3390/antiox12040871 - 3 Apr 2023
Cited by 1 | Viewed by 1499
Abstract
Oxidative stress (OS) plays an essential role in the pathophysiology of Duchenne muscular dystrophy (DMD). However, the actors that regulate OS need to be better studied. We aimed to evaluate whether NFE2-like bZIP transcription factor 2 (Nrf2), glutathione, malondialdehyde (MDA), and protein carbonyl [...] Read more.
Oxidative stress (OS) plays an essential role in the pathophysiology of Duchenne muscular dystrophy (DMD). However, the actors that regulate OS need to be better studied. We aimed to evaluate whether NFE2-like bZIP transcription factor 2 (Nrf2), glutathione, malondialdehyde (MDA), and protein carbonyl concentrations change according to the disease severity in DMD patients. Moreover, we assessed whether OS correlated with muscle injury, clinical characteristics, physical activity, and antioxidant food consumption (AFC). A total of 28 DMD patients participated in this study. OS markers, metabolic indicators, and enzymatic markers of muscle injury were measured in circulation. Muscle injury was measured with clinical scales, and physical activity and AFC were evaluated with questionnaires. Nrf2 concentration was lower (p ≤ 0.01), and malondialdehyde concentration was higher (p < 0.05) in non-ambulatory patients than in ambulatory patients. Nrf2 correlated with age (rho = −0.387), Vignos scale (rho = −0.328), GMFCS scale (rho = −0.399), and Brooke scale scores (rho = −0.371) (p < 0.05). MDA correlated with Vignos (rho = 0.317) and Brooke scale scores (rho = 0.414) (p ≤ 0.05). In conclusion, DMD patients with the worst muscle function had more significant oxidative damage and lower antioxidant function than DMD patients with better muscle function. Full article
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24 pages, 3144 KiB  
Article
High-Intensity Exercise Training Alters the Effect of N-Acetylcysteine on Exercise-Related Muscle Ionic Shifts in Men
by Anders K. Lemminger, Matteo Fiorenza, Kasper Eibye, Jens Bangsbo and Morten Hostrup
Antioxidants 2023, 12(1), 53; https://doi.org/10.3390/antiox12010053 - 27 Dec 2022
Cited by 3 | Viewed by 3454
Abstract
This study investigated whether high-intensity exercise training alters the effect of N-acetylcysteine (a precursor of antioxidant glutathione) on exercise-related muscle ionic shifts. We assigned 20 recreationally-active men to 6 weeks of high-intensity exercise training, comprising three weekly sessions of 4–10 × 20-s [...] Read more.
This study investigated whether high-intensity exercise training alters the effect of N-acetylcysteine (a precursor of antioxidant glutathione) on exercise-related muscle ionic shifts. We assigned 20 recreationally-active men to 6 weeks of high-intensity exercise training, comprising three weekly sessions of 4–10 × 20-s all-out bouts interspersed by 2 min recovery (SET, n = 10), or habitual lifestyle maintenance (n = 10). Before and after SET, we measured ionic shifts across the working muscle, using leg arteriovenous balance technique, during one-legged knee-extensor exercise to exhaustion with and without N-acetylcysteine infusion. Furthermore, we sampled vastus lateralis muscle biopsies for analyses of metabolites, mitochondrial respiratory function, and proteins regulating ion transport and antioxidant defense. SET lowered exercise-related H+, K+, lactate, and Na+ shifts and enhanced exercise performance by ≈45%. While N-acetylcysteine did not affect exercise-related ionic shifts before SET, it lowered H+, HCO3, and Na+ shifts after SET. SET enhanced muscle mitochondrial respiratory capacity and augmented the abundance of Na+/K+-ATPase subunits (α1 and β1), ATP-sensitive K+ channel subunit (Kir6.2), and monocarboxylate transporter-1, as well as superoxide dismutase-2 and glutathione peroxidase-1. Collectively, these findings demonstrate that high-intensity exercise training not only induces multiple adaptations that enhance the ability to counter exercise-related ionic shifts but also potentiates the effect of N-acetylcysteine on ionic shifts during exercise. Full article
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11 pages, 1963 KiB  
Article
Adding High-Intensity Interval Training to Classical Resistance Training Does Not Impede the Recovery from Inactivity-Induced Leg Muscle Weakness
by Tomas Venckunas, Marius Brazaitis, Audrius Snieckus, Mantas Mickevicius, Nerijus Eimantas, Andrejus Subocius, Dalia Mickeviciene, Håkan Westerblad and Sigitas Kamandulis
Antioxidants 2023, 12(1), 16; https://doi.org/10.3390/antiox12010016 - 22 Dec 2022
Viewed by 1613
Abstract
Inactivity is known to induce muscle weakness, and chronically increased levels of reactive oxygen species (ROS) are proposed to have a central causative role in this process. Intriguingly, high-intensity interval training (HIIT), which involves bursts of high ROS production, can have positive effects [...] Read more.
Inactivity is known to induce muscle weakness, and chronically increased levels of reactive oxygen species (ROS) are proposed to have a central causative role in this process. Intriguingly, high-intensity interval training (HIIT), which involves bursts of high ROS production, can have positive effects in pathological conditions with chronically increased ROS. Here, young male volunteers were exposed to 3 weeks of unloading of the dominant leg followed by 3 weeks of resistance training without (Ctrl group) or with the addition of all-out cycling HIIT. Changes in muscle thickness were assessed by ultrasonography, and contractile function was studied by measuring the torque during maximal voluntary contractions (MVC). The results show an ~6% decrease in vastus lateralis thickness after the unloading period, which was fully restored after the subsequent training period in both the Ctrl and HIIT groups. MVC torque was decreased by ~11% after the unloading period and recovered fully during the subsequent training period in both groups. All-out cycling performance was improved by the 3 weeks of HIIT. In conclusion, the decline in muscle size and function after 3 weeks of unloading was restored by 3 weeks of resistance training regardless of whether it was combined with HIIT. Full article
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16 pages, 2708 KiB  
Article
The Prevention of Ischemia-Reperfusion Injury in Elderly Rats after Lower Limb Tourniquet Use
by Borja Herrero de la Parte, Javier Roa-Esparza, Iñigo Cearra, Inmaculada Ruiz Montesinos, Daniel Alonso-Alconada, Ana Alonso-Varona, Carmen Mar Medina, Sira Iturrizaga Correcher and Ignacio García-Alonso
Antioxidants 2022, 11(10), 1936; https://doi.org/10.3390/antiox11101936 - 28 Sep 2022
Cited by 6 | Viewed by 1538
Abstract
Background: Lower limb ischemia-reperfusion injury (IRI-LL) is a common major complication of orthopedic surgery, especially in elderly patients. It has previously been demonstrated that folinic acid (FA) reduced IRI-LL damage in 3–4-month-old rats. This current work analyses the effect of FA in the [...] Read more.
Background: Lower limb ischemia-reperfusion injury (IRI-LL) is a common major complication of orthopedic surgery, especially in elderly patients. It has previously been demonstrated that folinic acid (FA) reduced IRI-LL damage in 3–4-month-old rats. This current work analyses the effect of FA in the prevention of IRI-LL in elderly animals. Methods: Forty-two 18-month-old male WAG/RijHsd rats were subjected to 3 h of ischemia. Eighteen animals received FA (2.5 mg/kg, ip) 20 min before the end of the ischemia period, while the other half received the same volume of saline solution. The animals were sacrificed after 3 h, 24 h, and 14 days of reperfusion for biochemical (tissue damage markers and electrolytes), histopathological studies of the gastrocnemius muscle and the daily assessment of the limb function by the Rota Rod test, respectively. Results: The administration of FA prior to the end of the ischemia period reduced the increase in LDH and CK observed in non-treated animals by 30–40% (p < 0.0001). When the histological sections were analyzed, FA was found to have reduced the number of damaged muscle fibers per field by 20% (60 ± 17.1 vs. 80.7 ± 16.4, p < 0.0001). The functional test revealed that FA also led to an improvement in the muscle function, assessed by the length of time that the animals kept running on the rod, compared to untreated animals. Conclusions: The administration of FA, prior to the end of the ischemic period, decreases the damage induced by IRI-LL, also achieving a faster recovery of mobility. Full article
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15 pages, 2242 KiB  
Article
Taurine Administration Counteracts Aging-Associated Impingement of Skeletal Muscle Regeneration by Reducing Inflammation and Oxidative Stress
by Alessandra Barbiera, Silvia Sorrentino, Damon Fard, Elisa Lepore, Gigliola Sica, Gabriella Dobrowolny, Luca Tamagnone and Bianca Maria Scicchitano
Antioxidants 2022, 11(5), 1016; https://doi.org/10.3390/antiox11051016 - 21 May 2022
Cited by 10 | Viewed by 4952
Abstract
Sarcopenia, which occurs during aging, is characterized by the gradual loss of skeletal muscle mass and function, resulting in a functional decline in physical abilities. Several factors contribute to the onset of sarcopenia, including reduced regenerative capacity, chronic low-grade inflammation, mitochondrial dysfunction, and [...] Read more.
Sarcopenia, which occurs during aging, is characterized by the gradual loss of skeletal muscle mass and function, resulting in a functional decline in physical abilities. Several factors contribute to the onset of sarcopenia, including reduced regenerative capacity, chronic low-grade inflammation, mitochondrial dysfunction, and increased oxidative stress, leading to the activation of catabolic pathways. Physical activity and adequate protein intake are considered effective strategies able to reduce the incidence and severity of sarcopenia by exerting beneficial effects in improving the muscular anabolic response during aging. Taurine is a non-essential amino acid that is highly expressed in mammalian tissues and, particularly, in skeletal muscle where it is involved in the regulation of biological processes and where it acts as an antioxidant and anti-inflammatory factor. Here, we evaluated whether taurine administration in old mice counteracts the physiopathological effects of aging in skeletal muscle. We showed that, in injured muscle, taurine enhances the regenerative process by downregulating the inflammatory response and preserving muscle fiber integrity. Moreover, taurine attenuates ROS production in aged muscles by maintaining a proper cellular redox balance, acting as an antioxidant molecule. Although further studies are needed to better elucidate the molecular mechanisms responsible for the beneficial effect of taurine on skeletal muscle homeostasis, these data demonstrate that taurine administration ameliorates the microenvironment allowing an efficient regenerative process and attenuation of the catabolic pathways related to the onset of sarcopenia. Full article
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