scholarly journals Antioxidant Treatment Reduces Formation of Structural Cores and Improves Muscle Function in RYR1Y522S/WTMice

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Antonio Michelucci ◽  
Alessandro De Marco ◽  
Flavia A. Guarnier ◽  
Feliciano Protasi ◽  
Simona Boncompagni
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Muscle Function ◽  
Structural Damage ◽  
Mitochondrial Damage ◽  
Mitochondrial Activity ◽  
Release Channel ◽  
Fiber Damage ◽  
Human Mutation

Central core disease (CCD) is a congenital myopathy linked to mutations in the ryanodine receptor type 1 (RYR1), the sarcoplasmic reticulum Ca2+release channel of skeletal muscle. CCD is characterized by formation of amorphouscoreswithin muscle fibers, lacking mitochondrial activity. In skeletal muscle of RYR1Y522S/WTknock-in mice, carrying a human mutation in RYR1 linked to malignant hyperthermia (MH) withcores, oxidative stress is elevated and fibers present severe mitochondrial damage andcores. We treated RYR1Y522S/WTmice with N-acetylcysteine (NAC), an antioxidant providedad libitumin drinking water for either 2 or 6 months. Our results show that 2 months of NAC treatment starting at 2 months of age, when mitochondrial and fiber damage was still minimal, (i) reduce formation ofunstructuredandcontracture cores, (ii) improve muscle function, and (iii) decrease mitochondrial damage. The beneficial effect of NAC treatment is also evident following 6 months of treatment starting at 4 months of age, when structural damage was at an advanced stage. NAC exerts its protective effect likely by lowering oxidative stress, as supported by the reduction of 3-NT and SOD2 levels. This work suggests that NAC administration is beneficial to prevent mitochondrial damage and formation ofcoresand improve muscle function in RYR1Y522S/WTmice.

scholarly journals Fourteen days of smoking cessation improves muscle fatigue resistance and reverses markers of systemic inflammation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mohammad Z. Darabseh ◽  
Thomas M. Maden-Wilkinson ◽  
George Welbourne ◽  
Rob C. I. Wüst ◽  
Nessar Ahmed ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Smoking Cessation ◽  
Muscle Fatigue ◽  
Fatigue Resistance ◽  
Systemic Inflammation ◽  
Muscle Function ◽  
Low Grade ◽  
Skeletal Muscle Function ◽  
Tnf Α

AbstractCigarette smoking has a negative effect on respiratory and skeletal muscle function and is a risk factor for various chronic diseases. To assess the effects of 14 days of smoking cessation on respiratory and skeletal muscle function, markers of inflammation and oxidative stress in humans. Spirometry, skeletal muscle function, circulating carboxyhaemoglobin levels, advanced glycation end products (AGEs), markers of oxidative stress and serum cytokines were measured in 38 non-smokers, and in 48 cigarette smokers at baseline and after 14 days of smoking cessation. Peak expiratory flow (p = 0.004) and forced expiratory volume in 1 s/forced vital capacity (p = 0.037) were lower in smokers compared to non-smokers but did not change significantly after smoking cessation. Smoking cessation increased skeletal muscle fatigue resistance (p < 0.001). Haemoglobin content, haematocrit, carboxyhaemoglobin, total AGEs, malondialdehyde, TNF-α, IL-2, IL-4, IL-6 and IL-10 (p < 0.05) levels were higher, and total antioxidant status (TAS), IL-12p70 and eosinophil numbers were lower (p < 0.05) in smokers. IL-4, IL-6, IL-10 and IL-12p70 had returned towards levels seen in non-smokers after 14 days smoking cessation (p < 0.05), and IL-2 and TNF-α showed a similar pattern but had not yet fully returned to levels seen in non-smokers. Haemoglobin, haematocrit, eosinophil count, AGEs, MDA and TAS did not significantly change with smoking cessation. Two weeks of smoking cessation was accompanied with an improved muscle fatigue resistance and a reduction in low-grade systemic inflammation in smokers.

Oxidative Stress in Skeletal Muscle Function and Dysfunction

2014 ◽  
pp. 373-390
Author(s):  
Carlos da Justa Pinheiro ◽  
Marco Salomão Fortes ◽  
Rui Curi
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Muscle Function ◽  
Skeletal Muscle Function

Impaired Function and Altered Morphology in the Skeletal Muscles of Adult Men and Women with Type 1 Diabetes

2021 ◽  
Author(s):  
Athan G Dial ◽  
Cynthia M F Monaco ◽  
Grace K Grafham ◽  
Tirth P Patel ◽  
Mark A Tarnopolsky ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Type 1 Diabetes ◽  
Muscle Function ◽  
Morphological Changes ◽  
Venous Blood ◽  
Accelerated Aging ◽  
Myosin Heavy Chain Isoforms ◽  
Hybrid Fibers ◽  
Skeletal Muscle Function

Abstract Context Previous investigations on skeletal muscle health in type 1 diabetes (T1D) has generally focused on later stages of disease progression where comorbidities are present and are posited as a primary mechanism of muscle dysfunction. Objective To investigate skeletal muscle function and morphology across the adult lifespan in those with and without T1D. Design Participants underwent maximal contraction (MVC) testing, resting muscle biopsy and venous blood sampling. Setting Procedures in this study were undertaken at the McMaster University Medical Centre. Participants Sixty-five healthy adult (18-78 years old) men/males and women/females [T1D=34; control=31] matched for age/biological sex/body mass index (BMI)/self-reported physical activity levels were included. Main Outcome Measures Our primary measure in this study was MVC, with supporting histological/immunofluorescent measures. Results After 35 years of age (‘older adults’), MVC declined quicker in T1D subjects compared to controls. Loss of strength in T1D was accompanied by morphological changes associated with accelerated aging. Type 1 myofiber grouping was higher in T1D, and the groups were larger and more numerous than in controls. Older T1D females exhibited more myofibers expressing multiple myosin heavy chain isoforms (hybrid fibers) than controls, another feature of accelerated aging. Conversely, T1D males exhibited a shift towards type 2 fibers, with less evidence of myofiber grouping or hybrid fibers. Conclusions These data suggest impairments to skeletal muscle function and morphology exist in T1D. The decline in strength with T1D is accelerated after 35 years of age and may be responsible for the earlier onset of frailty which characterizes those with diabetes.

scholarly journals Age-induced oxidative stress: how does it influence skeletal muscle quantity and quality?

2016 ◽  
Vol 121 (5) ◽  
pp. 1047-1052 ◽  
Author(s):  
Cory W. Baumann ◽  
Dongmin Kwak ◽  
Haiming M. Liu ◽  
LaDora V. Thompson
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Muscle Function ◽  
Strength Loss ◽  
Muscle Quality ◽  
Muscle Size ◽  
Nitrogen Species ◽  
Skeletal Muscle Function ◽  
Protein Balance ◽  
Ec Coupling

With advancing age, skeletal muscle function declines as a result of strength loss. These strength deficits are largely due to reductions in muscle size (i.e., quantity) and its intrinsic force-producing capacity (i.e., quality). Age-induced reductions in skeletal muscle quantity and quality can be the consequence of several factors, including accumulation of reactive oxygen and nitrogen species (ROS/RNS), also known as oxidative stress. Therefore, the purpose of this mini-review is to highlight the published literature that has demonstrated links between aging, oxidative stress, and skeletal muscle quantity or quality. In particular, we focused on how oxidative stress has the potential to reduce muscle quantity by shifting protein balance in a deficit, and muscle quality by impairing activation at the neuromuscular junction, excitation-contraction (EC) coupling at the ryanodine receptor (RyR), and cross-bridge cycling within the myofibrillar apparatus. Of these, muscle weakness due to EC coupling failure mediated by RyR dysfunction via oxidation and/or nitrosylation appears to be the strongest candidate based on the publications reviewed. However, it is clear that age-associated oxidative stress has the ability to alter strength through several mechanisms and at various locations of the muscle fiber.

240 FUNCTIONAL TRAITS OF CAT SPERM DURING DISTINCT MATURATION STATUS

2011 ◽  
Vol 23 (1) ◽  
pp. 218
Author(s):  
E. G. A. Perez ◽  
M. Nichi ◽  
C. A. Baptista Sobrinho ◽  
P. A. A. Góes ◽  
A. Dalmazzo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Structural Damage ◽  
Membrane Integrity ◽  
Domestic Cat ◽  
Lower Percentage ◽  
Mitochondrial Activity ◽  
Computer Assisted ◽  
Suitable Model ◽  
Sperm Analysis

Sperm recovery from the caudae epididymides can be advantageous for preserving semen of endangered animal species. In this context, the domestic cat is a suitable model for the study of sperm physiology in endangered feline species and the research on epididymal sperm preservation combined with the use of reproductive biotechnologies including intracytoplasmic sperm injection (ICSI). The aim of the present study was to examine the sperm collected from the cauda and caput of the cat epididymis using functional tests. Testicles and epididymides from 5 adult tomcats were collected by orchiectomy and maintained at 4°C for 4 h, until semen collection. Semen samples were collected from the epididymal tail and head by careful dissection. Samples were then analysed for motility by computer assisted sperm analysis (CASA; only for the caudal sperm). The 3-3′ diaminobenzidine stain was used as an index of mitochondrial activity, the eosin nigrosin stain as an index of membrane integrity, the simple stain (fast green/Bengal rose) as an index of acrosome integrity, and the measurement of thiobarbituric acid reactive substances (TBARS) as an index of lipid peroxidation. Statistical analysis was performed using the SAS System for Windows (SAS Institute Inc., Cary, NC, USA; least significant differences test and Spearman correlation; P < 0.05). No motility was observed in samples collected from the epididymal head, whereas samples from the tail showed 50.0 ± 4.2% motile spermatozoa. Surprisingly, more spermatozoa with high mitochondrial activity were found in the epididymal head than in samples from the tail (74.0 ± 3.5 v. 50.0 ± 4.3%, respectively). Similarly, samples collected from the head showed a higher susceptibility against the attack of ROS (31.9 ± 5.5 v. 16.3 ± 7.1 ng of TBARS/106 sperm, respectively). Furthermore, epididymal head sperm showed a lower percentage of sperm with intact membrane and a higher percentage of sperm with intact acrosome (44.9 ± 3.3 and 78.4 ± 1.8 v. 66.4 ± 4.2 and 56.7 ± 4.4%, respectively). Our results demonstrate that, during maturation, feline sperm are subjected to high oxidative stress, as shown by the lipid peroxidation assay, which would lead to structural damage to biomolecules, DNA, lipids, carbohydrates and proteins, as well as other cellular components, such as mitochondria, and acrosomal impairment. Similar results were found in humans, in which higher levels of oxidative stress occurred in the post-testicular environment. The plasma membrane seems to be more resistant to damages. This may be due to the described rearrangement in the lipid profile occurring during maturation, but studies to test this hypothesis are still underway.

239 POSSIBLE MECHANISMS OF SPERM DAMAGE CAUSED BY HEAT STRESS IN EUROPEAN BULLS RAISED IN TROPICAL ENVIRONMENTS

2011 ◽  
Vol 23 (1) ◽  
pp. 218
Author(s):  
M. Nichi ◽  
R. P. Bertolla ◽  
T. B. Soler ◽  
C. N. M. Cortada ◽  
R. M. Zuge ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heat Stress ◽  
Structural Damage ◽  
Membrane Integrity ◽  
Rank Test ◽  
Mitochondrial Activity ◽  
Enzymatic Antioxidants ◽  
High Positive Correlation ◽  
Positive Correlation ◽  
Tropical Environments

Previous studies have indicated that semen of heat-stressed bulls shows impaired mitochondrial activity and high levels of oxidative stress, which may cause structural damage to biomolecules, DNA, lipids, carbohydrates and proteins, as well as other cellular components (Nichi et al. 2006 Theriogenology 66, 822–828). Disruption of the sperm mitochondria could have a potential damaging effect not only on an individual sperm cell but also on the surrounding cells, especially regarding the sperm membrane, possibly due to the release of a high amount of reactive oxygen species (ROS) produced in this environment (rich in electrons) that would then lead to oxidative stress. To test this hypothesis, semen samples of 11 Simmental bulls kept in tropical environments were collected during the summer months. Semen was evaluated as follows: the 3-3′ diaminobenzidine stain (DAB) as an index of mitochondrial activity, the hypo-osmotic swelling test (HOST) as an index of membrane integrity, measurement of thiobarbituric acid reactive substances (TBARS) as an index of lipid peroxidation, and measurement of the enzymatic antioxidants superoxide dismutase, catalase and glutathione peroxidase activities. For correlation analysis, the Pearson test was used (variables were transformed when necessary), and for nonparametric variables, the Spearman rank test was used. A high positive correlation was found between sperm cells with highly active mitochondria (DAB class I) and the percentage of cells with intact membrane by HOST (r = 0.93; P < 0.05), and a negative correlation between the latter and the percentage of inactive mitochondria (r = –0.91; P < 0.05), indicating that the higher the percentage of cells showing impaired mitochondrial activity, the higher the percentage of cells with damaged membrane. There was also a positive correlation between TBARS and the percentage of cells with disrupted mitochondria (r = 0.86; P < 0.05), indicating that the higher the percentage of sperm with impaired mitochondrial activity, the higher the oxidative stress. No correlation existed between the enzymatic antioxidants and any of the variables studied. The results indicate that heat stress may lead to an increase in testicular ROS levels, overcoming the seminal antioxidant protection. This, in turn, may cause damage of the mitochondria and a subsequent release of more pro-oxidative substances, and an exponential increase of oxidative stress. Understanding these mechanisms may lead to more tailored antioxidant therapies in the future. The authors thank FAPESP for the scholarship and financial support.

scholarly journals Deficiency of triad junction and contraction in mutant skeletal muscle lacking junctophilin type 1

2001 ◽  
Vol 154 (5) ◽  
pp. 1059-1068 ◽  
Author(s):  
Koichi Ito ◽  
Shinji Komazaki ◽  
Kazushige Sasamoto ◽  
Morikatsu Yoshida ◽  
Miyuki Nishi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Plasma Membrane ◽  
Physiological Role ◽  
Mutant Mice ◽  
Functional Coupling ◽  
Release Channel ◽  
Signal Conversion ◽  
Triad Junction ◽  
Triad Junctions

In skeletal muscle excitation–contraction (E–C) coupling, the depolarization signal is converted from the intracellular Ca2+ store into Ca2+ release by functional coupling between the cell surface voltage sensor and the Ca2+ release channel on the sarcoplasmic reticulum (SR). The signal conversion occurs in the junctional membrane complex known as the triad junction, where the invaginated plasma membrane called the transverse-tubule (T-tubule) is pinched from both sides by SR membranes. Previous studies have suggested that junctophilins (JPs) contribute to the formation of the junctional membrane complexes by spanning the intracellular store membrane and interacting with the plasma membrane (PM) in excitable cells. Of the three JP subtypes, both type 1 (JP-1) and type 2 (JP-2) are abundantly expressed in skeletal muscle. To examine the physiological role of JP-1 in skeletal muscle, we generated mutant mice lacking JP-1. The JP-1 knockout mice showed no milk suckling and died shortly after birth. Ultrastructural analysis demonstrated that triad junctions were reduced in number, and that the SR was often structurally abnormal in the skeletal muscles of the mutant mice. The mutant muscle developed less contractile force (evoked by low-frequency electrical stimuli) and showed abnormal sensitivities to extracellular Ca2+. Our results indicate that JP-1 contributes to the construction of triad junctions and that it is essential for the efficiency of signal conversion during E–C coupling in skeletal muscle.

scholarly journals Potential Therapeutic Role of L-Carnitine in Skeletal Muscle Oxidative Stress and Atrophy Conditions

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Anna Montesano ◽  
Pamela Senesi ◽  
Livio Luzi ◽  
Stefano Benedini ◽  
Ileana Terruzzi
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Morphological Changes ◽  
Ubiquitin Proteasome System ◽  
Skeletal Muscle Atrophy ◽  
C2c12 Myotubes ◽  
Mitochondrial Activity ◽  
Potential Therapeutic Role ◽  
Essential Nutrient

The targeting of nutraceutical treatment to skeletal muscle damage is an emerging area of research, driven by the need for new therapies for a range of muscle-associated diseases. L-Carnitine (CARN) is an essential nutrient and plays a key role in mitochondrialβ-oxidation and in the ubiquitin-proteasome system regulation. As a dietary supplement to improve athletic performance, CARN has been studied for its potential to enhanceβ-oxidation. However, CARN effects on myogenesis, mitochondrial activity, and hypertrophy process are not completely elucidated. Thisin vitrostudy aims to investigate CARN role on skeletal muscle remodeling, differentiation process, and myotubes formation. We analyzed muscle differentiation and morphological features in C2C12 myoblasts exposed to 5 mM CARN. Our results showed that CARN was able to accelerate C2C12 myotubes formation and induce morphological changes, characterizing the start of hypertrophy process. In addition, CARN improved AKT activation and downstream cellular signaling pathways involved in skeletal muscle atrophy process prevention. Also, CARN positively regulated the pathways involved in oxidative stress defense. In this work, we provide an interesting novel mechanism of the potential therapeutic use of CARN to treat pathological conditions characterized by skeletal muscle morphological and functional impairment, oxidative stress production, and atrophy process in aging.

scholarly journals Nicotinic acid–adenine dinucleotide phosphate activates the skeletal muscle ryanodine receptor

2002 ◽  
Vol 367 (2) ◽  
pp. 423-431 ◽  
Author(s):  
Martin HOHENEGGER ◽  
Josef SUKO ◽  
Regina GSCHEIDLINGER ◽  
Helmut DROBNY ◽  
Andreas ZIDAR
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Nicotinic Acid ◽  
Ryanodine Receptor ◽  
Spatial Information ◽  
Single Channel ◽  
Reversal Potential ◽  
Open Probability ◽  
Release Channel

Calcium is a universal second messenger. The temporal and spatial information that is encoded in Ca2+-transients drives processes as diverse as neurotransmitter secretion, axonal outgrowth, immune responses and muscle contraction. Ca2+-release from intracellular Ca2+ stores can be triggered by diffusible second messengers like InsP3, cyclic ADP-ribose or nicotinic acid—adenine dinucleotide phosphate (NAADP). A target has not yet been identified for the latter messenger. In the present study we show that nanomolar concentrations of NAADP trigger Ca2+-release from skeletal muscle sarcoplasmic reticulum. This was due to a direct action on the Ca2+-release channel/ryanodine receptor type-1, since in single channel recordings, NAADP increased the open probability of the purified channel protein. The effects of NAADP on Ca2+-release and open probability of the ryanodine receptor occurred over a similar concentration range (EC5030nM) and were specific because (i) they were blocked by Ruthenium Red and ryanodine, (ii) the precursor of NAADP, NADP, was ineffective at equimolar concentrations, (iii) NAADP did not affect the conductance and reversal potential of the ryanodine receptor. Finally, we also detected an ADP-ribosyl cyclase activity in the sarcoplasmic reticulum fraction of skeletal muscle. This enzyme was not only capable of synthesizing cyclic GDP-ribose but also NAADP, with an activity of 0.25nmol/mg/min. Thus, we conclude that NAADP is generated in the vicinity of type 1 ryanodine receptor and leads to activation of this ion channel.

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