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International Journal of Molecular... Aug 2021The weight of skeletal muscle accounts for approximately 40% of the whole weight in a healthy individual, and the normal metabolism and motor function of the muscle are... (Review)
Review
The weight of skeletal muscle accounts for approximately 40% of the whole weight in a healthy individual, and the normal metabolism and motor function of the muscle are indispensable for healthy life. In addition, the skeletal muscle of the maxillofacial region plays an important role not only in eating and swallowing, but also in communication, such as facial expressions and conversations. In recent years, skeletal muscle atrophy has received worldwide attention as a serious health problem. However, the mechanism of skeletal muscle atrophy that has been clarified at present is insufficient, and a therapeutic method against skeletal muscle atrophy has not been established. This review provides views on the importance of skeletal muscle in the maxillofacial region and explains the differences between skeletal muscles in the maxillofacial region and other regions. We summarize the findings to change in gene expression in muscle remodeling and emphasize the advantages and disadvantages of denervation-induced skeletal muscle atrophy model. Finally, we discuss the newly discovered beneficial effects of natural compounds on skeletal muscle atrophy.
Topics: Animals; Biological Products; Denervation; Humans; Muscle, Skeletal; Muscular Atrophy
PubMed: 34361076
DOI: 10.3390/ijms22158310 -
American Journal of Physiology. Heart... Oct 2022Cardiac cachexia is a catabolic muscle-wasting syndrome observed in approximately 1 in 10 patients with heart failure. Increased skeletal muscle atrophy leads to frailty... (Review)
Review
Cardiac cachexia is a catabolic muscle-wasting syndrome observed in approximately 1 in 10 patients with heart failure. Increased skeletal muscle atrophy leads to frailty and limits mobility, which impacts quality of life, exacerbates clinical care, and is associated with higher rates of mortality. Heart failure is known to exhibit a wide range of prevalence and severity when examined across individuals of different ages and with comorbidities related to diabetes, renal failure, and pulmonary dysfunction. It is also recognized that men and women exhibit striking differences in the pathophysiology of heart failure, as well as skeletal muscle homeostasis. Given that both skeletal muscle and heart failure physiology are in part sex-dependent, the diagnosis and treatment of cachexia in patients with heart failure may depend on a comprehensive examination of how these organs interact. In this review, we explore the potential for sex-specific differences in cardiac cachexia. We summarize advantages and disadvantages of clinical methods used to measure muscle mass and function and provide alternative measurements that should be considered in preclinical studies. In addition, we summarize sex-dependent effects on muscle wasting in preclinical models of heart failure, disuse, and cancer. Lastly, we discuss the endocrine function of the heart and outline unanswered questions that could directly impact patient care.
Topics: Cachexia; Female; Heart Failure; Humans; Male; Muscle, Skeletal; Muscular Atrophy; Quality of Life
PubMed: 35960634
DOI: 10.1152/ajpheart.00187.2022 -
Journal of Cellular Physiology Sep 2017Skeletal muscle atrophy is the consequence of protein degradation exceeding protein synthesis. This arises for a multitude of reasons including the unloading of muscle... (Review)
Review
Skeletal muscle atrophy is the consequence of protein degradation exceeding protein synthesis. This arises for a multitude of reasons including the unloading of muscle during microgravity, post-surgery bedrest, immobilization of a limb after injury, and overall disuse of the musculature. The development of therapies prior to skeletal muscle atrophy settings to diminish protein degradation is scarce. Mitochondrial dysfunction is associated with skeletal muscle atrophy and contributes to the induction of protein degradation and cell apoptosis through increased levels of ROS observed with the loss of organelle function. ROS binds mtDNA, leading to its degradation and decreasing functionality. Mitochondrial transcription factor A (TFAM) will bind and coat mtDNA, protecting it from ROS and degradation while increasing mitochondrial function. Exercise stimulates cell signaling pathways that converge on and increase PGC-1α, a well-known activator of the transcription of TFAM and mitochondrial biogenesis. Therefore, in the present review we are proposing, separately, exercise and TFAM treatments prior to atrophic settings (muscle unloading or disuse) alleviate skeletal muscle atrophy through enhanced mitochondrial adaptations and function. Additionally, we hypothesize the combination of exercise and TFAM leads to a synergistic effect in targeting mitochondrial function to prevent skeletal muscle atrophy. J. Cell. Physiol. 232: 2348-2358, 2017. © 2016 The Authors. Journal of Cellular Physiology Published by © 2016 Wiley Periodicals, Inc.
Topics: Animals; Apoptosis; DNA, Mitochondrial; DNA-Binding Proteins; Exercise; Humans; Mitochondria, Muscle; Mitochondrial Proteins; Muscle Contraction; Muscle, Skeletal; Muscular Atrophy; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Protein Biosynthesis; Proteolysis; Reactive Oxygen Species; Signal Transduction; Transcription Factors
PubMed: 27966783
DOI: 10.1002/jcp.25737 -
International Journal of Biological... 2023Skeletal muscle wasting related to aging or pathological conditions is critically associated with the increased incidence and prevalence of secondary diseases including...
Skeletal muscle wasting related to aging or pathological conditions is critically associated with the increased incidence and prevalence of secondary diseases including cardiovascular diseases, metabolic syndromes, and chronic inflammations. Much effort is made to develop agents to enhance muscle metabolism and function. (. ; IO) is a mushroom popularly called chaga and has been widely employed as a folk medicine for inflammation, cardiovascular diseases, diabetes, and cancer in Eastern Europe and Asia. However, its effect on muscle health has not been explored. Here, we aimed to investigate the beneficial effect of IO extract in muscle regeneration and metabolism. The treatment of IO in C2C12 myoblasts led to increased myogenic differentiation and alleviation of dexamethasone-induced myotube atrophy. Network pharmacological analysis using the identified specific chemical constituents of IO extracts predicted protein kinase B (AKT)-dependent mechanisms to promote myogenesis and muscle regeneration. Consistently, IO treatment resulted in the activation of AKT, which suppressed muscle-specific ubiquitin E3 ligases induced by dexamethasone. IO treatment in mice improved the regeneration of cardiotoxin-injured muscles accompanied by elevated proliferation and differentiation of muscle stem cells. Furthermore, it elevated the mitochondrial content and muscle oxidative metabolism accompanied by the induction of peroxisome proliferator-activated receptor γ coactivator α (PGC-1α). Our current data suggest that IO is a promising natural agent in enhancing muscle regenerative capacity and oxidative metabolism thereby preventing muscle wasting.
Topics: Mice; Animals; Proto-Oncogene Proteins c-akt; Cardiovascular Diseases; Muscle, Skeletal; Muscular Atrophy; Oxidative Stress; Dexamethasone; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
PubMed: 37781506
DOI: 10.7150/ijbs.84970 -
Advances in Nutrition (Bethesda, Md.) Jul 2020Muscle atrophy and weakness occur as a consequence of disuse after musculoskeletal injury (MSI). The slow recovery and persistence of these deficits even after physical... (Review)
Review
Muscle atrophy and weakness occur as a consequence of disuse after musculoskeletal injury (MSI). The slow recovery and persistence of these deficits even after physical rehabilitation efforts indicate that interventions designed to attenuate muscle atrophy and protect muscle function are necessary to accelerate and optimize recovery from MSI. Evidence suggests that manipulating protein intake via dietary protein or free amino acid-based supplementation diminishes muscle atrophy and/or preserves muscle function in experimental models of disuse (i.e., immobilization and bed rest in healthy populations). However, this concept has rarely been considered in the context of disuse following MSI, which often occurs with some muscle activation during postinjury physical rehabilitation. Given that exercise sensitizes skeletal muscle to the anabolic effect of protein ingestion, early rehabilitation may act synergistically with dietary protein to protect muscle mass and function during postinjury disuse conditions. This narrative review explores mechanisms of skeletal muscle disuse atrophy and recent advances delineating the role of protein intake as a potential countermeasure. The possible synergistic effect of protein-based interventions and postinjury rehabilitation in attenuating muscle atrophy and weakness following MSI is also considered.
Topics: Dietary Proteins; Exercise; Humans; Muscle, Skeletal; Muscular Atrophy; Muscular Disorders, Atrophic
PubMed: 32167129
DOI: 10.1093/advances/nmaa015 -
Journal of Cachexia, Sarcopenia and... Jun 2021Cancer cachexia is a multifactorial debilitating syndrome that directly accounts for more than 20% of cancer deaths while there is no effective therapeutic approach for...
BACKGROUND
Cancer cachexia is a multifactorial debilitating syndrome that directly accounts for more than 20% of cancer deaths while there is no effective therapeutic approach for treatment of cancer cachexia. Carnosol (CS) is a bioactive diterpene compound present in Lamiaceae spp., which has been demonstrated to have antioxidant, anti-inflammatory, and anticancer properties. But its effects on cancer cachexia and the possible mechanism remain a mystery.
METHODS
The in vitro cell models of C2C12 myotube atrophy and 3T3-L1 mature adipocyte lipolysis were used to check the activities of CS and its synthesized analogues. C26 tumour-bearing BALB/c mice were applied as the animal model to examine their therapeutic effects on cancer cachexia in vivo. Levels of related signal proteins in both in vitro and in vivo experiments were examined using western blotting to study the possible mechanisms.
RESULTS
Carnosol and its analogues [dimethyl-carnosol (DCS) and dimethyl-carnosol-D6 (DCSD)] alleviated myotube atrophy of C2C12 myotubes and lipolysis of 3T3-L1 adipocytes in vitro. Interestingly, CS and its analogues exhibited stronger inhibitive effects on muscle atrophy induced by tumour necrosis factor-α (TNF-α) (CS, P < 0.001; DCS, P < 0.001; DCSD, P < 0.001) in C2C12 myoblasts than on muscle atrophy induced by IL-6 (CS, P < 0.05; DCS, P = 0.08; DCSD, P < 0.05). In a C26 tumour-bearing mice model, administration of CS or its analogue DCSD significantly prevented body weight loss without affecting tumour size. At the end of the experiment, the body weight of mice treated with CS and DCSD was significantly increased by 11.09% (P < 0.01) and 11.38% (P < 0.01) compared with that of the C26 model group. CS and DCSD also improved the weight loss of epididymal adipose tissue in C26 model mice by 176.6% (P < 0.01) and 48.2% (P < 0.05) increase, respectively. CS and DCSD treatment partly preserved gastrocnemius myofibres cross-sectional area. CS treatment decreased the serum level of TNF-α (-95.02%, P < 0.01) but not IL-6 in C26 tumour-bearing mice. Inhibition on NF-κB and activation of Akt signalling pathway were involved in the ameliorating effects of CS and its analogues on muscle wasting both in vitro and in vivo. CS and its analogues also alleviated adipose tissue loss by inhibiting NF-κB and AMPK signalling pathways both in vitro and in vivo.
CONCLUSIONS
CS and its analogues exhibited anticachexia effects mainly by inhibiting TNF-α/NF-κB pathway and decreasing muscle and adipose tissue loss. CS and its analogues might be promising drug candidates for the treatment of cancer cachexia.
Topics: Abietanes; Animals; Cachexia; Lipolysis; Mice; Mice, Inbred BALB C; Muscular Atrophy; Neoplasms
PubMed: 33951335
DOI: 10.1002/jcsm.12710 -
Journal of Cellular and Molecular... Oct 2021Sepsis and sepsis-induced skeletal muscle atrophy are common in patients in intensive care units with high mortality, while the mechanisms are controversial and...
Sepsis and sepsis-induced skeletal muscle atrophy are common in patients in intensive care units with high mortality, while the mechanisms are controversial and complicated. In the present study, the atrophy of skeletal muscle was evaluated in sepsis mouse model as well as the apoptosis of muscle fibres. Sepsis induced atrophy of skeletal muscle and apoptosis of myofibres in vivo and in vitro. In cell-based in vitro experiments, lipopolysaccharide (LPS) stimulation also inhibited the proliferation of myoblasts. At the molecular level, the expression of polo-like kinase 1 (PLK1) and phosphorylated protein kinase B (p-AKT) was decreased. Overexpression of PLK1 partly rescued LPS-induced apoptosis, proliferation suppression and atrophy in C2C12 cells. Furthermore, inhibiting the AKT pathway deteriorated LPS-induced atrophy in PLK1-overexpressing C2C12 myotubes. PLK1 was found to participate in regulating apoptosis and E3 ubiquitin ligase activity in C2C12 cells. Taken together, these results indicate that sepsis induces skeletal muscle atrophy by promoting apoptosis of muscle fibres and inhibiting proliferation of myoblasts via regulation of the PLK1-AKT pathway. These findings enhance understanding of the mechanism of sepsis-induced skeletal muscle atrophy.
Topics: Animals; Apoptosis; Biomarkers; Cell Cycle Proteins; Cell Line; Cell Survival; Disease Models, Animal; Immunohistochemistry; Immunophenotyping; Male; Mice; Models, Biological; Muscular Atrophy; Myoblasts; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; RNA, Small Interfering; Sepsis; Signal Transduction; Ubiquitin-Protein Ligases; Polo-Like Kinase 1
PubMed: 34514712
DOI: 10.1111/jcmm.16921 -
Nature Materials Feb 2023While mechanical stimulation is known to regulate a wide range of biological processes at the cellular and tissue levels, its medical use for tissue regeneration and...
While mechanical stimulation is known to regulate a wide range of biological processes at the cellular and tissue levels, its medical use for tissue regeneration and rehabilitation has been limited by the availability of suitable devices. Here we present a mechanically active gel-elastomer-nitinol tissue adhesive (MAGENTA) that generates and delivers muscle-contraction-mimicking stimulation to a target tissue with programmed strength and frequency. MAGENTA consists of a shape memory alloy spring that enables actuation up to 40% strain, and an adhesive that efficiently transmits the actuation to the underlying tissue. MAGENTA activates mechanosensing pathways involving yes-associated protein and myocardin-related transcription factor A, and increases the rate of muscle protein synthesis. Disuse muscles treated with MAGENTA exhibit greater size and weight, and generate higher forces compared to untreated muscles, demonstrating the prevention of atrophy. MAGENTA thus has promising applications in the treatment of muscle atrophy and regenerative medicine.
Topics: Humans; Muscle, Skeletal; Tissue Adhesives; Rosaniline Dyes; Muscular Atrophy; Muscle Contraction
PubMed: 36357687
DOI: 10.1038/s41563-022-01396-x -
Journal of Cellular and Molecular... Sep 2022Homeostasis in skeletal muscle is sustained by the balance of functional and physical interactions between muscle and myofibre microenvironment. Various factors, such as... (Review)
Review
Homeostasis in skeletal muscle is sustained by the balance of functional and physical interactions between muscle and myofibre microenvironment. Various factors, such as ageing, disuse and denervation, tip the balance and induce skeletal muscle atrophy. Skeletal muscle atrophy, which involves complex physiological and biochemical changes, is accompanied by adverse outcomes and even increased mortality. Multiple studies have investigated the role of neutrophils in atrophied skeletal muscles; however, neutrophil intrusion in muscle is still a polemical knot. As technical obstacles have been overcome, people have gradually discovered new functions of neutrophils. The classical view of neutrophils is no longer applicable to their biological characteristics. To date, no clear association between the hidden injurious effect of neutrophil intrusion and muscle atrophy has been convincingly proven. Throughout this review, we have discussed the neutrophil activities that mediate muscle atrophy for distinct disease occurrences. Hopefully, this review will help both clinicians and researchers of skeletal muscle atrophy with relevant targets to further explore efficient medical interventions and treatments.
Topics: Aging; Humans; Muscle, Skeletal; Muscular Atrophy; Neutrophils
PubMed: 35899367
DOI: 10.1111/jcmm.17495 -
Current Opinion in Clinical Nutrition... May 2012This review will discuss the evidence both for and against the concept that reactive oxygen species (ROS) play an important role in the regulation of inactivity-induced... (Review)
Review
PURPOSE OF REVIEW
This review will discuss the evidence both for and against the concept that reactive oxygen species (ROS) play an important role in the regulation of inactivity-induced skeletal muscle atrophy.
RECENT FINDINGS
It is well established that prolonged skeletal muscle inactivity causes muscle fiber atrophy and a decrease in muscle force production. This disuse-induced muscle atrophy is the consequence of a loss in muscle protein resulting from increased protein degradation and decreased protein synthesis. Recent studies suggest that oxidative stress can influence cell-signaling pathways that regulate both muscle protein breakdown and synthesis during prolonged periods of disuse. Specifically, it is feasible that increased ROS production in muscle fibers can promote increased proteolysis and also depress protein synthesis during periods of skeletal muscle inactivity.
SUMMARY
Although it is established that oxidants can participate in the regulation of protein turnover in cells, there remains debate as to whether oxidative stress is required for disuse skeletal muscle atrophy. Nonetheless, based on emerging evidence we conclude that increased ROS production in skeletal muscles significantly contributes to inactivity-induced muscle atrophy.
Topics: Humans; Muscle Proteins; Muscle, Skeletal; Muscular Atrophy; Muscular Disorders, Atrophic; Oxidative Stress; Proteolysis; Reactive Oxygen Species; Signal Transduction
PubMed: 22466926
DOI: 10.1097/MCO.0b013e328352b4c2