Cells

Research

13 pages, 1543 KiB

Open AccessArticle

Redox Balance Differentially Affects Biomechanics in Permeabilized Single Muscle Fibres—Active and Passive Force Assessments with the Myorobot

by Mena Michael, Larisa Kovbasyuk, Paul Ritter, Michael B. Reid, Oliver Friedrich and Michael Haug

Cells 2022, 11(23), 3715; https://doi.org/10.3390/cells11233715 - 22 Nov 2022

Cited by 2 | Viewed by 1651

Abstract

An oxidizing redox state imposes unique effects on the contractile properties of muscle. Permeabilized fibres show reduced active force generation in the presence of H₂O₂. However, our knowledge about the muscle fibre’s elasticity or flexibility is limited due to [...] Read more.

An oxidizing redox state imposes unique effects on the contractile properties of muscle. Permeabilized fibres show reduced active force generation in the presence of H₂O₂. However, our knowledge about the muscle fibre’s elasticity or flexibility is limited due to shortcomings in assessing the passive stress–strain properties, mostly due to technically limited experimental setups. The MyoRobot is an automated biomechatronics platform that is well-capable of not only investigating calcium responsiveness of active contraction but also features precise stretch actuation to examine the passive stress–strain behaviour. Both were carried out in a consecutive recording sequence on the same fibre for 10 single fibres in total. We denote a significantly diminished maximum calcium-saturated force for fibres exposed to ≥500 µM H₂O₂, with no marked alteration of the pCa50 value. In contrast to active contraction (e.g., maximum isometric force activation), passive restoration stress (force per area) significantly increases for fibres exposed to an oxidizing environment, as they showed a non-linear stress–strain relationship. Our data support the idea that a highly oxidizing environment promotes non-linear fibre stiffening and confirms that our MyoRobot platform is a suitable tool for investigating redox-related changes in muscle biomechanics. Full article

(This article belongs to the Special Issue Redox Control of Cell Signaling in Cardiac and Skeletal Muscle)

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11 pages, 2923 KiB

Open AccessArticle

Patient-Derived Pancreatic Cancer Cells Induce C2C12 Myotube Atrophy by Releasing Hsp70 and Hsp90

by Hong-Yu Wu, Jose G. Trevino, Bing-Liang Fang, Andrea N. Riner, Vignesh Vudatha, Guo-Hua Zhang and Yi-Ping Li

Cells 2022, 11(17), 2756; https://doi.org/10.3390/cells11172756 - 3 Sep 2022

Cited by 10 | Viewed by 2975

Abstract

Pancreatic cancer (PC) patients are highly prone to cachexia, a lethal wasting syndrome featuring muscle wasting with an undefined etiology. Recent data indicate that certain murine cancer cells induce muscle wasting by releasing Hsp70 and Hsp90 through extracellular vesicles (EVs) to activate p38β [...] Read more.

Pancreatic cancer (PC) patients are highly prone to cachexia, a lethal wasting syndrome featuring muscle wasting with an undefined etiology. Recent data indicate that certain murine cancer cells induce muscle wasting by releasing Hsp70 and Hsp90 through extracellular vesicles (EVs) to activate p38β MAPK-mediated catabolic pathways primarily through Toll-like receptor 4 (TLR4). However, whether human PC induces cachexia through releasing Hsp70 and Hsp90 is undetermined. Here, we investigated whether patient-derived PC cells induce muscle cell atrophy directly through this mechanism. We compared cancer cells isolated from patient-derived xenografts (PDX) from three PC patients who had cachexia (PCC) with those of three early-stage lung cancer patients without cachexia (LCC) and two renal cancer patients who were not prone to cachexia (RCC). We observed small increases of Hsp70 and Hsp90 released by LCC and RCC in comparison to non-cancer control cells (NCC). However, PCC released markedly higher levels of Hsp70 and Hsp90 (~ 6-fold on average) than LCC and RCC. In addition, PCC released similarly increased levels of Hsp70/90-containing EVs. In contrast to RCC and LCC, PCC-conditioned media induced a potent catabolic response in C2C12 myotubes including the activation of p38 MAPK and transcription factor C/EBPβ, upregulation of E3 ligases UBR2 and MAFbx, and increase of autophagy marker LC3-II, resulting in the loss of the myosin heavy chain (MHC ~50%) and myotube diameter (~60%). Importantly, the catabolic response was attenuated by Hsp70- and Hsp90-neutralizing antibodies in a dose-dependent manner. These data suggest that human PC cells release high levels of Hsp70 and Hsp90 that induce muscle atrophy through a direct action on muscle cells. Full article

(This article belongs to the Special Issue Redox Control of Cell Signaling in Cardiac and Skeletal Muscle)

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14 pages, 1032 KiB

Open AccessArticle

Reversible Thiol Oxidation Increases Mitochondrial Electron Transport Complex Enzyme Activity but Not Respiration in Cardiomyocytes from Patients with End-Stage Heart Failure

by Ravi A. Kumar, Trace Thome, Omar M. Sharaf, Terence E. Ryan, George J. Arnaoutakis, Eric I. Jeng and Leonardo F. Ferreira

Cells 2022, 11(15), 2292; https://doi.org/10.3390/cells11152292 - 25 Jul 2022

Cited by 3 | Viewed by 2145

Abstract

Cardiomyocyte dysfunction in patients with end-stage heart failure with reduced ejection fraction (HFrEF) stems from mitochondrial dysfunction, which contributes to an energetic crisis. Mitochondrial dysfunction reportedly relates to increased markers of oxidative stress, but the impact of reversible thiol oxidation on myocardial mitochondrial [...] Read more.

Cardiomyocyte dysfunction in patients with end-stage heart failure with reduced ejection fraction (HFrEF) stems from mitochondrial dysfunction, which contributes to an energetic crisis. Mitochondrial dysfunction reportedly relates to increased markers of oxidative stress, but the impact of reversible thiol oxidation on myocardial mitochondrial function in patients with HFrEF has not been investigated. In the present study, we assessed mitochondrial function in ventricular biopsies from patients with end-stage HFrEF in the presence and absence of the thiol-reducing agent dithiothreitol (DTT). Isolated mitochondria exposed to DTT had increased enzyme activity of complexes I (p = 0.009) and III (p = 0.018) of the electron transport system, while complexes II (p = 0.630) and IV (p = 0.926) showed no changes. However, increased enzyme activity did not carry over to measurements of mitochondrial respiration in permeabilized bundles. Oxidative phosphorylation conductance (p = 0.439), maximal respiration (p = 0.312), and ADP sensitivity (p = 0.514) were unchanged by 5 mM DTT treatment. These results indicate that mitochondrial function can be modulated through reversible thiol oxidation, but other components of mitochondrial energy transfer are rate limiting in end-stage HFrEF. Optimal therapies to normalize cardiac mitochondrial respiration in patients with end-stage HFrEF may benefit from interventions to reverse thiol oxidation, which limits complex I and III activities. Full article

(This article belongs to the Special Issue Redox Control of Cell Signaling in Cardiac and Skeletal Muscle)

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17 pages, 3836 KiB

Open AccessArticle

Effects of Omega-3 and Antioxidant Cocktail Supplement on Prolonged Bed Rest: Results from Serum Proteome and Sphingolipids Analysis

by Pietro Barbacini, Dieter Blottner, Daniele Capitanio, Gabor Trautmann, Katharina Block, Enrica Torretta, Manuela Moriggi, Michele Salanova and Cecilia Gelfi

Cells 2022, 11(13), 2120; https://doi.org/10.3390/cells11132120 - 5 Jul 2022

Cited by 5 | Viewed by 2136

Abstract

Physical inactivity or prolonged bed rest (BR) induces muscle deconditioning in old and young subjects and can increase the cardiovascular disease risk (CVD) with dysregulation of the lipemic profile. Nutritional interventions, combining molecules such as polyphenols, vitamins and essential fatty acids, can influence [...] Read more.

Physical inactivity or prolonged bed rest (BR) induces muscle deconditioning in old and young subjects and can increase the cardiovascular disease risk (CVD) with dysregulation of the lipemic profile. Nutritional interventions, combining molecules such as polyphenols, vitamins and essential fatty acids, can influence some metabolic features associated with physical inactivity and decrease the reactive oxidative and nitrosative stress (RONS). The aim of this study was to detect circulating molecules correlated with BR in serum of healthy male subjects enrolled in a 60-day BR protocol to evaluate a nutritional intervention with an antioxidant cocktail as a disuse countermeasure (Toulouse COCKTAIL study). The serum proteome, sphingolipidome and nitrosoproteome were analyzed adopting different mass spectrometry-based approaches. Results in placebo-treated BR subjects indicated a marked decrease of proteins associated with high-density lipoproteins (HDL) involved in lipemic homeostasis not found in the cocktail-treated BR group. Moreover, long-chain ceramides decreased while sphingomyelin increased in the BR cocktail-treated group. In placebo, the ratio of S-nitrosylated/total protein increased for apolipoprotein D and several proteins were over-nitrosylated. In cocktail-treated BR subjects, the majority of protein showed a pattern of under-nitrosylation, except for ceruloplasmin and hemopexin, which were over-nitrosylated. Collectively, data indicate a positive effect of the cocktail in preserving lipemic and RONS homeostasis in extended disuse conditions. Full article

(This article belongs to the Special Issue Redox Control of Cell Signaling in Cardiac and Skeletal Muscle)

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11 pages, 1614 KiB

Open AccessArticle

Activation of Calpain Contributes to Mechanical Ventilation-Induced Depression of Protein Synthesis in Diaphragm Muscle

by Hayden W. Hyatt, Mustafa Ozdemir, Matthew P. Bomkamp and Scott K. Powers

Cells 2022, 11(6), 1028; https://doi.org/10.3390/cells11061028 - 18 Mar 2022

Cited by 6 | Viewed by 2600

Abstract

Mechanical ventilation (MV) is a clinical tool that provides respiratory support to patients unable to maintain adequate alveolar ventilation on their own. Although MV is often a life-saving intervention in critically ill patients, an undesired side-effect of prolonged MV is the rapid occurrence [...] Read more.

Mechanical ventilation (MV) is a clinical tool that provides respiratory support to patients unable to maintain adequate alveolar ventilation on their own. Although MV is often a life-saving intervention in critically ill patients, an undesired side-effect of prolonged MV is the rapid occurrence of diaphragmatic atrophy due to accelerated proteolysis and depressed protein synthesis. Investigations into the mechanism(s) responsible for MV-induced diaphragmatic atrophy reveal that activation of the calcium-activated protease, calpain, plays a key role in accelerating proteolysis in diaphragm muscle fibers. Moreover, active calpain has been reported to block signaling events that promote protein synthesis (i.e., inhibition of mammalian target of rapamycin (mTOR) activation). While this finding suggests that active calpain can depress muscle protein synthesis, this postulate has not been experimentally verified. Therefore, we tested the hypothesis that active calpain plays a key role in the MV-induced depression of both anabolic signaling events and protein synthesis in the diaphragm muscle. MV-induced activation of calpain in diaphragm muscle fibers was prevented by transgene overexpression of calpastatin, an endogenous inhibitor of calpain. Our findings indicate that overexpression of calpastatin averts MV-induced activation of calpain in diaphragm fibers and rescues the MV-induced depression of protein synthesis in the diaphragm muscle. Surprisingly, deterrence of calpain activation did not impede the MV-induced inhibition of key anabolic signaling events including mTOR activation. However, blockade of calpain activation prevented the calpain-induced cleavage of glutaminyl-tRNA synthetase in diaphragm fibers; this finding is potentially important because aminoacyl-tRNA synthetases play a central role in protein synthesis. Regardless of the mechanism(s) responsible for calpain’s depression of protein synthesis, these results provide the first evidence that active calpain plays an important role in promoting the MV-induced depression of protein synthesis within diaphragm fibers. Full article

(This article belongs to the Special Issue Redox Control of Cell Signaling in Cardiac and Skeletal Muscle)

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13 pages, 2537 KiB

Open AccessArticle

X-ROS Signaling Depends on Length-Dependent Calcium Buffering by Troponin

by Sarita Limbu, Benjamin L. Prosser, William J. Lederer, Christopher W. Ward and Mohsin S. Jafri

Cells 2021, 10(5), 1189; https://doi.org/10.3390/cells10051189 - 13 May 2021

Cited by 6 | Viewed by 2432

Abstract

The stretching of a cardiomyocyte leads to the increased production of reactive oxygen species that increases ryanodine receptor open probability through a process termed X-ROS signaling. The stretching of the myocyte also increases the calcium affinity of myofilament Troponin C, which increases its [...] Read more.

The stretching of a cardiomyocyte leads to the increased production of reactive oxygen species that increases ryanodine receptor open probability through a process termed X-ROS signaling. The stretching of the myocyte also increases the calcium affinity of myofilament Troponin C, which increases its calcium buffering capacity. Here, an integrative experimental and modeling study is pursued to explain the interplay of length-dependent changes in calcium buffering by troponin and stretch-activated X-ROS calcium signaling. Using this combination, we show that the troponin C-dependent increase in myoplasmic calcium buffering during myocyte stretching largely offsets the X-ROS-dependent increase in calcium release from the sarcoplasmic reticulum. The combination of modeling and experiment are further informed by the elimination of length-dependent changes to troponin C calcium binding in the presence of blebbistatin. Here, the model suggests that it is the X-ROS signaling-dependent Ca²⁺ release increase that serves to maintain free myoplasmic calcium concentrations during a change in myocyte length. Together, our experimental and modeling approaches have further defined the relative contributions of X-ROS signaling and the length-dependent calcium buffering by troponin in shaping the myoplasmic calcium transient. Full article

(This article belongs to the Special Issue Redox Control of Cell Signaling in Cardiac and Skeletal Muscle)

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Review

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19 pages, 406 KiB

Open AccessReview

Reactive Oxygen and Nitrogen Species (RONS) and Cytokines—Myokines Involved in Glucose Uptake and Insulin Resistance in Skeletal Muscle

by Paola Llanos and Jesus Palomero

Cells 2022, 11(24), 4008; https://doi.org/10.3390/cells11244008 - 11 Dec 2022

Cited by 9 | Viewed by 2566

Abstract

Insulin resistance onset in skeletal muscle is characterized by the impairment of insulin signaling, which reduces the internalization of glucose, known as glucose uptake, into the cell. Therefore, there is a deficit of intracellular glucose, which is the main source for energy production [...] Read more.

Insulin resistance onset in skeletal muscle is characterized by the impairment of insulin signaling, which reduces the internalization of glucose, known as glucose uptake, into the cell. Therefore, there is a deficit of intracellular glucose, which is the main source for energy production in the cell. This may compromise cellular viability and functions, leading to pathological dysfunction. Skeletal muscle fibers continuously generate reactive oxygen and nitrogen species (RONS). An excess of RONS produces oxidative distress, which may evoke cellular damage and dysfunction. However, a moderate level of RONS, which is called oxidative eustress, is critical to maintain, modulate and regulate cellular functions through reversible interactions between RONS and the components of cellular signaling pathways that control those functions, such as the facilitation of glucose uptake. The skeletal muscle releases peptides called myokines that may have endocrine and paracrine effects. Some myokines bind to specific receptors in skeletal muscle fibers and might interact with cellular signaling pathways, such as PI3K/Akt and AMPK, and facilitate glucose uptake. In addition, there are cytokines, which are peptides produced by non-skeletal muscle cells, that bind to receptors at the plasma membrane of skeletal muscle cells and interact with the cellular signaling pathways, facilitating glucose uptake. RONS, myokines and cytokines might be acting on the same signaling pathways that facilitate glucose uptake in skeletal muscle. However, the experimental studies are limited and scarce. The aim of this review is to highlight the current knowledge regarding the role of RONS, myokines and cytokines as potential signals that facilitate glucose uptake in skeletal muscle. In addition, we encourage researchers in the field to lead and undertake investigations to uncover the fundamentals of glucose uptake evoked by RONS, myokines, and cytokines. Full article

(This article belongs to the Special Issue Redox Control of Cell Signaling in Cardiac and Skeletal Muscle)

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11 pages, 571 KiB

Open AccessReview

Deficient Sarcolemma Repair in ALS: A Novel Mechanism with Therapeutic Potential

by Ang Li, Jianxun Yi, Xuejun Li, Li Dong, Lyle W. Ostrow, Jianjie Ma and Jingsong Zhou

Cells 2022, 11(20), 3263; https://doi.org/10.3390/cells11203263 - 17 Oct 2022

Cited by 1 | Viewed by 2422

Abstract

The plasma membrane (sarcolemma) of skeletal muscle myofibers is susceptible to injury caused by physical and chemical stresses during normal daily movement and/or under disease conditions. These acute plasma membrane disruptions are normally compensated by an intrinsic membrane resealing process involving interactions of [...] Read more.

The plasma membrane (sarcolemma) of skeletal muscle myofibers is susceptible to injury caused by physical and chemical stresses during normal daily movement and/or under disease conditions. These acute plasma membrane disruptions are normally compensated by an intrinsic membrane resealing process involving interactions of multiple intracellular proteins including dysferlin, annexin, caveolin, and Mitsugumin 53 (MG53)/TRIM72. There is new evidence for compromised muscle sarcolemma repair mechanisms in Amyotrophic Lateral Sclerosis (ALS). Mitochondrial dysfunction in proximity to neuromuscular junctions (NMJs) increases oxidative stress, triggering MG53 aggregation and loss of its function. Compromised membrane repair further worsens sarcolemma fragility and amplifies oxidative stress in a vicious cycle. This article is to review existing literature supporting the concept that ALS is a disease of oxidative-stress induced disruption of muscle membrane repair that compromise the integrity of the NMJs and hence augmenting muscle membrane repair mechanisms could represent a viable therapeutic strategy for ALS. Full article

(This article belongs to the Special Issue Redox Control of Cell Signaling in Cardiac and Skeletal Muscle)

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18 pages, 1323 KiB

Open AccessReview

Glucose 6-P Dehydrogenase—An Antioxidant Enzyme with Regulatory Functions in Skeletal Muscle during Exercise

by Esther García-Domínguez, Aitor Carretero, Aurora Viña-Almunia, Julio Domenech-Fernandez, Gloria Olaso-Gonzalez, Jose Viña and Mari Carmen Gomez-Cabrera

Cells 2022, 11(19), 3041; https://doi.org/10.3390/cells11193041 - 28 Sep 2022

Cited by 12 | Viewed by 4689

Abstract

Hypomorphic Glucose 6-P dehydrogenase (G6PD) alleles, which cause G6PD deficiency, affect around one in twenty people worldwide. The high incidence of G6PD deficiency may reflect an evolutionary adaptation to the widespread prevalence of malaria, as G6PD-deficient red blood cells (RBCs) are hostile to [...] Read more.

Hypomorphic Glucose 6-P dehydrogenase (G6PD) alleles, which cause G6PD deficiency, affect around one in twenty people worldwide. The high incidence of G6PD deficiency may reflect an evolutionary adaptation to the widespread prevalence of malaria, as G6PD-deficient red blood cells (RBCs) are hostile to the malaria parasites that infect humans. Although medical interest in this enzyme deficiency has been mainly focused on RBCs, more recent evidence suggests that there are broader implications for G6PD deficiency in health, including in skeletal muscle diseases. G6PD catalyzes the rate-limiting step in the pentose phosphate pathway (PPP), which provides the precursors of nucleotide synthesis for DNA replication as well as reduced nicotinamide adenine dinucleotide phosphate (NADPH). NADPH is involved in the detoxification of cellular reactive oxygen species (ROS) and de novo lipid synthesis. An association between increased PPP activity and the stimulation of cell growth has been reported in different tissues including the skeletal muscle, liver, and kidney. PPP activity is increased in skeletal muscle during embryogenesis, denervation, ischemia, mechanical overload, the injection of myonecrotic agents, and physical exercise. In fact, the highest relative increase in the activity of skeletal muscle enzymes after one bout of exhaustive exercise is that of G6PD, suggesting that the activation of the PPP occurs in skeletal muscle to provide substrates for muscle repair. The age-associated loss in muscle mass and strength leads to a decrease in G6PD activity and protein content in skeletal muscle. G6PD overexpression in Drosophila Melanogaster and mice protects against metabolic stress, oxidative damage, and age-associated functional decline, and results in an extended median lifespan. This review discusses whether the well-known positive effects of exercise training in skeletal muscle are mediated through an increase in G6PD. Full article

(This article belongs to the Special Issue Redox Control of Cell Signaling in Cardiac and Skeletal Muscle)

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26 pages, 1840 KiB

Open AccessReview

Impact of Exercise and Aging on Mitochondrial Homeostasis in Skeletal Muscle: Roles of ROS and Epigenetics

by Jialin Li, Zhe Wang, Can Li, Yu Song, Yan Wang, Hai Bo and Yong Zhang

Cells 2022, 11(13), 2086; https://doi.org/10.3390/cells11132086 - 30 Jun 2022

Cited by 21 | Viewed by 7396

Abstract

Aging causes degenerative changes such as epigenetic changes and mitochondrial dysfunction in skeletal muscle. Exercise can upregulate muscle mitochondrial homeostasis and enhance antioxidant capacity and represents an effective treatment to prevent muscle aging. Epigenetic changes such as DNA methylation, histone posttranslational modifications, and [...] Read more.

Aging causes degenerative changes such as epigenetic changes and mitochondrial dysfunction in skeletal muscle. Exercise can upregulate muscle mitochondrial homeostasis and enhance antioxidant capacity and represents an effective treatment to prevent muscle aging. Epigenetic changes such as DNA methylation, histone posttranslational modifications, and microRNA expression are involved in the regulation of exercise-induced adaptive changes in muscle mitochondria. Reactive oxygen species (ROS) play an important role in signaling molecules in exercise-induced muscle mitochondrial health benefits, and strong evidence emphasizes that exercise-induced ROS can regulate gene expression via epigenetic mechanisms. The majority of mitochondrial proteins are imported into mitochondria from the cytosol, so mitochondrial homeostasis is regulated by nuclear epigenetic mechanisms. Exercise can reverse aging-induced changes in myokine expression by modulating epigenetic mechanisms. In this review, we provide an overview of the role of exercise-generated ROS in the regulation of mitochondrial homeostasis mediated by epigenetic mechanisms. In addition, the potential epigenetic mechanisms involved in exercise-induced myokine expression are reviewed. Full article

(This article belongs to the Special Issue Redox Control of Cell Signaling in Cardiac and Skeletal Muscle)

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41 pages, 4505 KiB

Open AccessReview

p66Shc in Cardiovascular Pathology

by Landon Haslem, Jennifer M. Hays and Franklin A. Hays

Cells 2022, 11(11), 1855; https://doi.org/10.3390/cells11111855 - 6 Jun 2022

Cited by 14 | Viewed by 3812

Abstract

p66Shc is a widely expressed protein that governs a variety of cardiovascular pathologies by generating, and exacerbating, pro-apoptotic ROS signals. Here, we review p66Shc’s connections to reactive oxygen species, expression, localization, and discuss p66Shc signaling and mitochondrial functions. Emphasis is placed on recent [...] Read more.

p66Shc is a widely expressed protein that governs a variety of cardiovascular pathologies by generating, and exacerbating, pro-apoptotic ROS signals. Here, we review p66Shc’s connections to reactive oxygen species, expression, localization, and discuss p66Shc signaling and mitochondrial functions. Emphasis is placed on recent p66Shc mitochondrial function discoveries including structure/function relationships, ROS identity and regulation, mechanistic insights, and how p66Shc-cyt c interactions can influence p66Shc mitochondrial function. Based on recent findings, a new p66Shc mitochondrial function model is also put forth wherein p66Shc acts as a rheostat that can promote or antagonize apoptosis. A discussion of how the revised p66Shc model fits previous findings in p66Shc-mediated cardiovascular pathology follows. Full article

(This article belongs to the Special Issue Redox Control of Cell Signaling in Cardiac and Skeletal Muscle)

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14 pages, 1872 KiB

Open AccessReview

Redox Control of Signalling Responses to Contractile Activity and Ageing in Skeletal Muscle

by Malcolm J. Jackson, Natalie Pollock, Caroline Staunton, Samantha Jones and Anne McArdle

Cells 2022, 11(10), 1698; https://doi.org/10.3390/cells11101698 - 20 May 2022

Cited by 13 | Viewed by 2875

Abstract

Research over almost 40 years has established that reactive oxygen species are generated at different sites in skeletal muscle and that the generation of these species is increased by various forms of exercise. Initially, this was thought to be potentially deleterious to skeletal [...] Read more.

Research over almost 40 years has established that reactive oxygen species are generated at different sites in skeletal muscle and that the generation of these species is increased by various forms of exercise. Initially, this was thought to be potentially deleterious to skeletal muscle and other tissues, but more recent data have identified key roles of these species in muscle adaptations to exercise. The aim of this review is to summarise our current understanding of these redox signalling roles of reactive oxygen species in mediating responses of muscle to contractile activity, with a particular focus on the effects of ageing on these processes. In addition, we provide evidence that disruption of the redox status of muscle mitochondria resulting from age-associated denervation of muscle fibres may be an important factor leading to an attenuation of some muscle responses to contractile activity, and we speculate on potential mechanisms involved. Full article

(This article belongs to the Special Issue Redox Control of Cell Signaling in Cardiac and Skeletal Muscle)

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20 pages, 873 KiB

Open AccessReview

Redox Implications of Extreme Task Performance: The Case in Driver Athletes

by Michael B. Reid

Cells 2022, 11(5), 899; https://doi.org/10.3390/cells11050899 - 5 Mar 2022

Cited by 2 | Viewed by 4018

Abstract

Redox homeostasis and redox-mediated signaling mechanisms are fundamental elements of human biology. Physiological levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) modulate a range of functional processes at the cellular, tissue, and systemic levels in healthy humans. Conversely, excess ROS [...] Read more.

Redox homeostasis and redox-mediated signaling mechanisms are fundamental elements of human biology. Physiological levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) modulate a range of functional processes at the cellular, tissue, and systemic levels in healthy humans. Conversely, excess ROS or RNS activity can disrupt function, impairing the performance of daily activities. This article analyzes the impact of redox mechanisms on extreme task performance. Such activities (a) require complex motor skills, (b) are physically demanding, (c) are performed in an extreme environment, (d) require high-level executive function, and (e) pose an imminent risk of injury or death. The current analysis utilizes race car driving as a representative example. The physiological challenges of this extreme task include physical exertion, g loading, vibration, heat exposure, dehydration, noise, mental demands, and emotional factors. Each of these challenges stimulates ROS signaling, RNS signaling, or both, alters redox homeostasis, and exerts pro-oxidant effects at either the tissue or systemic levels. These redox mechanisms appear to promote physiological stress during race car driving and impair the performance of driver athletes. Full article

(This article belongs to the Special Issue Redox Control of Cell Signaling in Cardiac and Skeletal Muscle)

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25 pages, 1312 KiB

Open AccessEditor’s ChoiceReview

Maintenance of NAD+ Homeostasis in Skeletal Muscle during Aging and Exercise

by Li Li Ji and Dongwook Yeo

Cells 2022, 11(4), 710; https://doi.org/10.3390/cells11040710 - 17 Feb 2022

Cited by 22 | Viewed by 9615

Abstract

Nicotinamide adenine dinucleotide (NAD) is a versatile chemical compound serving as a coenzyme in metabolic pathways and as a substrate to support the enzymatic functions of sirtuins (SIRTs), poly (ADP-ribose) polymerase-1 (PARP-1), and cyclic ADP ribose hydrolase (CD38). Under normal physiological conditions, NAD+ [...] Read more.

Nicotinamide adenine dinucleotide (NAD) is a versatile chemical compound serving as a coenzyme in metabolic pathways and as a substrate to support the enzymatic functions of sirtuins (SIRTs), poly (ADP-ribose) polymerase-1 (PARP-1), and cyclic ADP ribose hydrolase (CD38). Under normal physiological conditions, NAD+ consumption is matched by its synthesis primarily via the salvage pathway catalyzed by nicotinamide phosphoribosyltransferase (NAMPT). However, aging and muscular contraction enhance NAD+ utilization, whereas NAD+ replenishment is limited by cellular sources of NAD+ precursors and/or enzyme expression. This paper will briefly review NAD+ metabolic functions, its roles in regulating cell signaling, mechanisms of its degradation and biosynthesis, and major challenges to maintaining its cellular level in skeletal muscle. The effects of aging, physical exercise, and dietary supplementation on NAD+ homeostasis will be highlighted based on recent literature. Full article

(This article belongs to the Special Issue Redox Control of Cell Signaling in Cardiac and Skeletal Muscle)

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Other

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7 pages, 257 KiB

Open AccessOpinion

Athletes’ Mesenchymal Stem Cells Could Be the Best Choice for Cell Therapy in Omicron-Infected Patients

by Mona Saheli, Kayvan Khoramipour, Massoud Vosough, Abbas Piryaei, Masoud Rahmati and Katsuhiko Suzuki

Cells 2022, 11(12), 1926; https://doi.org/10.3390/cells11121926 - 14 Jun 2022

Cited by 3 | Viewed by 2519

Abstract

New severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, Omicron, contains 32 mutations that have caused a high incidence of breakthrough infections or re-infections. These mutations have reduced vaccine protection against Omicron and other new emerging variants. This highlights the need to find [...] Read more.

New severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, Omicron, contains 32 mutations that have caused a high incidence of breakthrough infections or re-infections. These mutations have reduced vaccine protection against Omicron and other new emerging variants. This highlights the need to find effective treatment, which is suggested to be stem cell-based therapy. Stem cells could support respiratory epithelial cells and they could restore alveolar bioenergetics. In addition, they can increase the secretion of immunomodulatory cytokines. However, after transplantation, cell survival and growth rate are low because of an inappropriate microenvironment, and stem cells face ischemia, inflammation, and oxidative stress in the transplantation niche which reduces the cells’ survival and growth. Exercise-training can upregulate antioxidant, anti-inflammatory, and anti-apoptotic defense mechanisms and increase growth signaling, thereby improving transplanted cells’ survival and growth. Hence, using athletes’ stem cells may increase stem-cell therapy outcomes in Omicron-affected patients. Full article

(This article belongs to the Special Issue Redox Control of Cell Signaling in Cardiac and Skeletal Muscle)

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