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Scott K Powers - One of the best experts on this subject based on the ideXlab platform.
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Disease-Induced Skeletal Muscle Atrophy and Fatigue
Medicine and Science in Sports and Exercise, 2016Co-Authors: Scott K Powers, Gordon S. Lynch, Kate T. Murphy, Michael B. Reid, Inge ZijdewindAbstract:Numerous health problems, including acute critical illness, cancer, diseases associated with chronic inflammation, and neurological disorders, often result in skeletal Muscle weakness and fatigue. Disease-related Muscle Atrophy and fatigue is an important clinical problem because acquired skeletal Muscle weakness can increase the duration of hospitalization, result in exercise limitation, and contribute to a poor quality of life. Importantly, skeletal Muscle Atrophy is also associated with increased morbidity and mortality of patients. Therefore, improving our understanding of the mechanism(s) responsible for skeletal Muscle weakness and fatigue in patients is a required first step to develop clinical protocols to prevent these skeletal Muscle problems. This review will highlight the consequences and potential mechanisms responsible for skeletal Muscle Atrophy and fatigue in patients experiencing acute critical illness, cancer, chronic inflammatory diseases, and neurological disorders.
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redox control of skeletal Muscle Atrophy
Free Radical Biology and Medicine, 2016Co-Authors: Scott K Powers, Aaron B Morton, Ashley J SmuderAbstract:Skeletal Muscles comprise the largest organ system in the body and play an essential role in body movement, breathing, and glucose homeostasis. Skeletal Muscle is also an important endocrine organ that contributes to the health of numerous body organs. Therefore, maintaining healthy skeletal Muscles is important to support overall health of the body. Prolonged periods of Muscle inactivity (e.g., bed rest or limb immobilization) or chronic inflammatory diseases (i.e., cancer, kidney failure, etc.) result in skeletal Muscle Atrophy. An excessive loss of Muscle mass is associated with a poor prognosis in several diseases and significant Muscle weakness impairs the quality of life. The skeletal Muscle Atrophy that occurs in response to inflammatory diseases or prolonged inactivity is often associated with both oxidative and nitrosative stress. In this report, we critically review the experimental evidence that provides support for a causative link between oxidants and Muscle Atrophy. More specifically, this review will debate the sources of oxidant production in skeletal Muscle undergoing Atrophy as well as provide a detailed discussion on how reactive oxygen species and reactive nitrogen species modulate the signaling pathways that regulate both protein synthesis and protein breakdown.
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Can Antioxidants Protect Against Disuse Muscle Atrophy
Sports Medicine, 2014Co-Authors: Scott K PowersAbstract:Long periods of skeletal Muscle inactivity (e.g. prolonged bed rest or limb immobilization) results in a loss of Muscle protein and fibre Atrophy. This disuse-induced Muscle Atrophy is due to both a decrease in protein synthesis and increased protein breakdown. Although numerous factors contribute to the regulation of the rates of protein breakdown and synthesis in skeletal Muscle, it has been established that prolonged Muscle inactivity results in increased radical production in the inactive Muscle fibres. Further, this increase in radical production plays an important role in the regulation of redox-sensitive signalling pathways that regulate both protein synthesis and proteolysis in skeletal Muscle. Indeed, it was suggested over 20 years ago that antioxidant supplementation has the potential to protect skeletal Muscles against inactivity-induced fibre Atrophy. Since this original proposal, experimental evidence has implied that a few compounds with antioxidant properties are capable of delaying inactivity-induced Muscle Atrophy. The objective of this review is to discuss the role that radicals play in the regulation of inactivity-induced skeletal Muscle Atrophy and to provide an analysis of the recent literature indicating that specific antioxidants have the potential to defer disuse Muscle Atrophy.
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mitochondrial signaling contributes to disuse Muscle Atrophy
American Journal of Physiology-endocrinology and Metabolism, 2012Co-Authors: Scott K Powers, Michael P Wiggs, Jose Alberto Duarte, Murat A Zergeroglu, Haydar A DemirelAbstract:It is well established that long durations of bed rest, limb immobilization, or reduced activity in respiratory Muscles during mechanical ventilation results in skeletal Muscle Atrophy in humans and other animals. The idea that mitochondrial damage/dysfunction contributes to disuse Muscle Atrophy originated over 40 years ago. These early studies were largely descriptive and did not provide unequivocal evidence that mitochondria play a primary role in disuse Muscle Atrophy. However, recent experiments have provided direct evidence connecting mitochondrial dysfunction to Muscle Atrophy. Numerous studies have described changes in mitochondria shape, number, and function in skeletal Muscles exposed to prolonged periods of inactivity. Furthermore, recent evidence indicates that increased mitochondrial ROS production plays a key signaling role in both immobilization-induced limb Muscle Atrophy and diaphragmatic Atrophy occurring during prolonged mechanical ventilation. Moreover, new evidence reveals that, during denervation-induced Muscle Atrophy, increased mitochondrial fragmentation due to fission is a required signaling event that activates the AMPK-FoxO3 signaling axis, which induces the expression of Atrophy genes, protein breakdown, and ultimately Muscle Atrophy. Collectively, these findings highlight the importance of future research to better understand the mitochondrial signaling mechanisms that contribute to disuse Muscle Atrophy and to develop novel therapeutic interventions for prevention of inactivity-induced skeletal Muscle Atrophy.
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mitochondrial targeted antioxidants protect skeletal Muscle against immobilization induced Muscle Atrophy
Journal of Applied Physiology, 2011Co-Authors: Ashley J Smuder, Andreas N Kavazis, Oh Sung Kwon, Hazel H Szeto, Scott K PowersAbstract:Prolonged periods of muscular inactivity (e.g., limb immobilization) result in skeletal Muscle Atrophy. Although it is established that reactive oxygen species (ROS) play a role in inactivity-induced skeletal Muscle Atrophy, the cellular pathway(s) responsible for inactivity-induced ROS production remain(s) unclear. To investigate this important issue, we tested the hypothesis that elevated mitochondrial ROS production contributes to immobilization-induced increases in oxidative stress, protease activation, and myofiber Atrophy in skeletal Muscle. Cause-and-effect was determined by administration of a novel mitochondrial-targeted antioxidant (SS-31) to prevent immobilization-induced mitochondrial ROS production in skeletal Muscle fibers. Compared with ambulatory controls, 14 days of Muscle immobilization resulted in significant Muscle Atrophy, along with increased mitochondrial ROS production, Muscle oxidative damage, and protease activation. Importantly, treatment with a mitochondrial-targeted antioxidant attenuated the inactivity-induced increase in mitochondrial ROS production and prevented oxidative stress, protease activation, and myofiber Atrophy. These results support the hypothesis that redox disturbances contribute to immobilization-induced skeletal Muscle Atrophy and that mitochondria are an important source of ROS production in Muscle fibers during prolonged periods of inactivity.
Jean-paul Thissen - One of the best experts on this subject based on the ideXlab platform.
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glucocorticoid induced skeletal Muscle Atrophy
The International Journal of Biochemistry & Cell Biology, 2013Co-Authors: Olivier Schakman, Stéphanie Kalista, Caroline Barbe, Audrey Loumaye, Jean-paul ThissenAbstract:Many pathological states characterized by Muscle Atrophy (e.g., sepsis, cachexia, starvation, metabolic acidosis and severe insulinopenia) are associated with an increase in circulating glucocorticoids (GC) levels, suggesting that GC could trigger the Muscle Atrophy observed in these conditions. GC-induced Muscle Atrophy is characterized by fast-twitch, glycolytic Muscles Atrophy illustrated by decreased fiber cross-sectional area and reduced myofibrillar protein content. GC-induced Muscle Atrophy results from increased protein breakdown and decreased protein synthesis. Increased Muscle proteolysis, in particular through the activation of the ubiquitin proteasome and the lysosomal systems, is considered to play a major role in the catabolic action of GC. The stimulation by GC of these two proteolytic systems is mediated through the increased expression of several Atrogenes ("genes involved in Atrophy"), such as FOXO, Atrogin-1, and MuRF-1. The inhibitory effect of GC on Muscle protein synthesis is thought to result mainly from the inhibition of the mTOR/S6 kinase 1 pathway. These changes in Muscle protein turnover could be explained by changes in the Muscle production of two growth factors, namely Insulin-like Growth Factor (IGF)-I, a Muscle anabolic growth factor and Myostatin, a Muscle catabolic growth factor. This review will discuss the recent progress made in the understanding of the mechanisms involved in GC-induced Muscle Atrophy and consider the implications of these advancements in the development of new therapeutic approaches for treating GC-induced myopathy. This article is part of a Directed Issue entitled: Molecular basis of Muscle wasting.
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Glucocorticoid-induced skeletal Muscle Atrophy ☆
The International Journal of Biochemistry & Cell Biology, 2013Co-Authors: Olivier Schakman, Stéphanie Kalista, Caroline Barbe, Audrey Loumaye, Jean-paul ThissenAbstract:Many pathological states characterized by Muscle Atrophy (e.g., sepsis, cachexia, starvation, metabolic acidosis and severe insulinopenia) are associated with an increase in circulating glucocorticoids (GC) levels, suggesting that GC could trigger the Muscle Atrophy observed in these conditions. GC-induced Muscle Atrophy is characterized by fast-twitch, glycolytic Muscles Atrophy illustrated by decreased fiber cross-sectional area and reduced myofibrillar protein content. GC-induced Muscle Atrophy results from increased protein breakdown and decreased protein synthesis. Increased Muscle proteolysis, in particular through the activation of the ubiquitin proteasome and the lysosomal systems, is considered to play a major role in the catabolic action of GC. The stimulation by GC of these two proteolytic systems is mediated through the increased expression of several Atrogenes ("genes involved in Atrophy"), such as FOXO, Atrogin-1, and MuRF-1. The inhibitory effect of GC on Muscle protein synthesis is thought to result mainly from the inhibition of the mTOR/S6 kinase 1 pathway. These changes in Muscle protein turnover could be explained by changes in the Muscle production of two growth factors, namely Insulin-like Growth Factor (IGF)-I, a Muscle anabolic growth factor and Myostatin, a Muscle catabolic growth factor. This review will discuss the recent progress made in the understanding of the mechanisms involved in GC-induced Muscle Atrophy and consider the implications of these advancements in the development of new therapeutic approaches for treating GC-induced myopathy. This article is part of a Directed Issue entitled: Molecular basis of Muscle wasting.
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Mechanisms of Muscle Atrophy induced by glucocorticoids.
Hormone research, 2009Co-Authors: Olivier Schakman, Hélène Gilson, Stéphanie Kalista, Jean-paul ThissenAbstract:Many pathological states characterized by Muscle Atrophy (e.g., sepsis, cachexia, starvation, metabolic acidosis and severe insulinopenia) are associated with an increase in circulating glucocorticoid (GC) levels, suggesting that GC could trigger the Muscle Atrophy observed in these conditions. GC-induced Muscle Atrophy results from decreased protein synthesis and increased protein degradation. The inhibitory effect of GCs on protein synthesis is thought to result mainly from the inhibition of the p70 ribosomal S6 protein kinase. The stimulatory effect of GCs on Muscle proteolysis results from the activation of two major cellular proteolytic systems: ubiquitin proteasome and lysosomal systems. The decrease in Muscle production of insulin-like growth factor I (IGF-I), a Muscle anabolic growth factor, could contribute to GC-induced Muscle Atrophy. By activating the phosphatidylinositol-3-kinase/Akt pathway, IGF-I overrides GC action to stunt Muscle Atrophy. Evidence also indicates that increased production of myostatin, a catabolic growth factor, could play a critical role in GC-induced Muscle Atrophy. Recent progress in understanding the role of growth factors in GC-induced Muscle Atrophy allows investigation into new therapies to minimize this myopathy. Copyright 2009 S. Karger AG, Basel.
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Mechanisms of Muscle Atrophy induced by glucocorticoids.
Hormone Research in Paediatrics, 2009Co-Authors: Olivier Schakman, Hélène Gilson, Stéphanie Kalista, Jean-paul ThissenAbstract:Background: Many pathological states characterized by Muscle Atrophy (e.g., sepsis, cachexia, starvation, metabolic acidosis and severe insulinopenia) are associated with an increase in circulating glucocorticoid (GC) levels, suggesting that GC could trigger the Muscle Atrophy observed in these conditions. GC-induced Muscle Atrophy results from decreased protein synthesis and increased protein degradation. The inhibitory effect of GCs on protein synthesis is thought to result mainly from the inhibition of the p70 ribosomal S6 protein kinase. The stimulatory effect of GCs on Muscle proteolysis results from the activation of two major cellular proteolytic systems: ubiquitin proteasome and lysosomal systems. The decrease in Muscle production of insulin-like growth factor I (IGF-I), a Muscle anabolic growth factor, could contribute to GC-induced Muscle Atrophy. By activating the phosphatidylinositol-3-kinase/Akt pathway, IGF-I overrides GC action to stunt Muscle Atrophy. Evidence also indicates that increased production of myostatin, a catabolic growth factor, could play a critical role in GC-induced Muscle Atrophy. Conclusions: Recent progress in understanding the role of growth factors in GC-induced Muscle Atrophy allows investigation into new therapies to minimize this myopathy.
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myostatin gene deletion prevents glucocorticoid induced Muscle Atrophy
Endocrinology, 2007Co-Authors: Hélène Gilson, Olivier Schakman, Lydie Combaret, Pascale Lause, L Grobet, Didier Attaix, Jeanmarie Ketelslegers, Jean-paul ThissenAbstract:Glucocorticoids mediate Muscle Atrophy in many catabolic states. Myostatin expression, a negative regulator of Muscle growth, is increased by glucocorticoids and myostatin overexpression is associated with lower Muscle mass. This suggests that myostatin is required for the catabolic effects of glucocorticoids. We therefore investigated whether myostatin gene disruption could prevent Muscle Atrophy caused by glucocorticoids. Male myostatin knockout (KO) and wild-type mice were subjected to dexamethasone treatment (1 mg/kg.d for 10 d or 5 mg/kg.d for 4 d). In wild-type mice, daily administration of low-dose dexamethasone for 10 d resulted in Muscle Atrophy (tibialis anterior: -15%; gastrocnemius: -13%; P < 0.01) due to 15% decrease in the Muscle fiber cross-sectional area (1621 +/- 31 vs. 1918 +/- 64 microm(2), P < 0.01). In KO mice, there was no reduction of Muscle mass nor fiber cross-sectional area after dexamethasone treatment. Muscle Atrophy after 4 d of high-dose dexamethasone was associated with increased mRNA of enzymes involved in proteolytic pathways (atrogin-1, Muscle ring finger 1, and cathepsin L) and increased chymotrypsin-like proteasomal activity. In contrast, the mRNA of these enzymes and the proteasomal activity were not significantly affected by dexamethasone in KO mice. Muscle IGF-I mRNA was paradoxically decreased in KO mice (-35%, P < 0.05); this was associated with a potentially compensatory increase of IGF-II expression in both saline and dexamethasone-treated KO mice (2-fold, P < 0.01). In conclusion, our results show that myostatin deletion prevents Muscle Atrophy in glucocorticoid-treated mice, by blunting the glucocorticoid-induced enhanced proteolysis, and suggest an important role of myostatin in Muscle Atrophy caused by glucocorticoids.
Olivier Schakman - One of the best experts on this subject based on the ideXlab platform.
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glucocorticoid induced skeletal Muscle Atrophy
The International Journal of Biochemistry & Cell Biology, 2013Co-Authors: Olivier Schakman, Stéphanie Kalista, Caroline Barbe, Audrey Loumaye, Jean-paul ThissenAbstract:Many pathological states characterized by Muscle Atrophy (e.g., sepsis, cachexia, starvation, metabolic acidosis and severe insulinopenia) are associated with an increase in circulating glucocorticoids (GC) levels, suggesting that GC could trigger the Muscle Atrophy observed in these conditions. GC-induced Muscle Atrophy is characterized by fast-twitch, glycolytic Muscles Atrophy illustrated by decreased fiber cross-sectional area and reduced myofibrillar protein content. GC-induced Muscle Atrophy results from increased protein breakdown and decreased protein synthesis. Increased Muscle proteolysis, in particular through the activation of the ubiquitin proteasome and the lysosomal systems, is considered to play a major role in the catabolic action of GC. The stimulation by GC of these two proteolytic systems is mediated through the increased expression of several Atrogenes ("genes involved in Atrophy"), such as FOXO, Atrogin-1, and MuRF-1. The inhibitory effect of GC on Muscle protein synthesis is thought to result mainly from the inhibition of the mTOR/S6 kinase 1 pathway. These changes in Muscle protein turnover could be explained by changes in the Muscle production of two growth factors, namely Insulin-like Growth Factor (IGF)-I, a Muscle anabolic growth factor and Myostatin, a Muscle catabolic growth factor. This review will discuss the recent progress made in the understanding of the mechanisms involved in GC-induced Muscle Atrophy and consider the implications of these advancements in the development of new therapeutic approaches for treating GC-induced myopathy. This article is part of a Directed Issue entitled: Molecular basis of Muscle wasting.
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Glucocorticoid-induced skeletal Muscle Atrophy ☆
The International Journal of Biochemistry & Cell Biology, 2013Co-Authors: Olivier Schakman, Stéphanie Kalista, Caroline Barbe, Audrey Loumaye, Jean-paul ThissenAbstract:Many pathological states characterized by Muscle Atrophy (e.g., sepsis, cachexia, starvation, metabolic acidosis and severe insulinopenia) are associated with an increase in circulating glucocorticoids (GC) levels, suggesting that GC could trigger the Muscle Atrophy observed in these conditions. GC-induced Muscle Atrophy is characterized by fast-twitch, glycolytic Muscles Atrophy illustrated by decreased fiber cross-sectional area and reduced myofibrillar protein content. GC-induced Muscle Atrophy results from increased protein breakdown and decreased protein synthesis. Increased Muscle proteolysis, in particular through the activation of the ubiquitin proteasome and the lysosomal systems, is considered to play a major role in the catabolic action of GC. The stimulation by GC of these two proteolytic systems is mediated through the increased expression of several Atrogenes ("genes involved in Atrophy"), such as FOXO, Atrogin-1, and MuRF-1. The inhibitory effect of GC on Muscle protein synthesis is thought to result mainly from the inhibition of the mTOR/S6 kinase 1 pathway. These changes in Muscle protein turnover could be explained by changes in the Muscle production of two growth factors, namely Insulin-like Growth Factor (IGF)-I, a Muscle anabolic growth factor and Myostatin, a Muscle catabolic growth factor. This review will discuss the recent progress made in the understanding of the mechanisms involved in GC-induced Muscle Atrophy and consider the implications of these advancements in the development of new therapeutic approaches for treating GC-induced myopathy. This article is part of a Directed Issue entitled: Molecular basis of Muscle wasting.
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Mechanisms of Muscle Atrophy induced by glucocorticoids.
Hormone research, 2009Co-Authors: Olivier Schakman, Hélène Gilson, Stéphanie Kalista, Jean-paul ThissenAbstract:Many pathological states characterized by Muscle Atrophy (e.g., sepsis, cachexia, starvation, metabolic acidosis and severe insulinopenia) are associated with an increase in circulating glucocorticoid (GC) levels, suggesting that GC could trigger the Muscle Atrophy observed in these conditions. GC-induced Muscle Atrophy results from decreased protein synthesis and increased protein degradation. The inhibitory effect of GCs on protein synthesis is thought to result mainly from the inhibition of the p70 ribosomal S6 protein kinase. The stimulatory effect of GCs on Muscle proteolysis results from the activation of two major cellular proteolytic systems: ubiquitin proteasome and lysosomal systems. The decrease in Muscle production of insulin-like growth factor I (IGF-I), a Muscle anabolic growth factor, could contribute to GC-induced Muscle Atrophy. By activating the phosphatidylinositol-3-kinase/Akt pathway, IGF-I overrides GC action to stunt Muscle Atrophy. Evidence also indicates that increased production of myostatin, a catabolic growth factor, could play a critical role in GC-induced Muscle Atrophy. Recent progress in understanding the role of growth factors in GC-induced Muscle Atrophy allows investigation into new therapies to minimize this myopathy. Copyright 2009 S. Karger AG, Basel.
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Mechanisms of Muscle Atrophy induced by glucocorticoids.
Hormone Research in Paediatrics, 2009Co-Authors: Olivier Schakman, Hélène Gilson, Stéphanie Kalista, Jean-paul ThissenAbstract:Background: Many pathological states characterized by Muscle Atrophy (e.g., sepsis, cachexia, starvation, metabolic acidosis and severe insulinopenia) are associated with an increase in circulating glucocorticoid (GC) levels, suggesting that GC could trigger the Muscle Atrophy observed in these conditions. GC-induced Muscle Atrophy results from decreased protein synthesis and increased protein degradation. The inhibitory effect of GCs on protein synthesis is thought to result mainly from the inhibition of the p70 ribosomal S6 protein kinase. The stimulatory effect of GCs on Muscle proteolysis results from the activation of two major cellular proteolytic systems: ubiquitin proteasome and lysosomal systems. The decrease in Muscle production of insulin-like growth factor I (IGF-I), a Muscle anabolic growth factor, could contribute to GC-induced Muscle Atrophy. By activating the phosphatidylinositol-3-kinase/Akt pathway, IGF-I overrides GC action to stunt Muscle Atrophy. Evidence also indicates that increased production of myostatin, a catabolic growth factor, could play a critical role in GC-induced Muscle Atrophy. Conclusions: Recent progress in understanding the role of growth factors in GC-induced Muscle Atrophy allows investigation into new therapies to minimize this myopathy.
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Role of IGF-I in glucocorticoid-induced Muscle Atrophy
2009Co-Authors: Olivier SchakmanAbstract:Increased circulating levels of glucocorticoids observed in many catabolic conditions play a major role in the induction of Muscle Atrophy. Indeed, inhibition of glucocorticoid action by glucocorticoid receptor antagonist attenuates and, in some cases, abolishes Muscle Atrophy. Circulating and tissue levels of IGF-I, a growth factor that stimulates the development of Muscle mass, are frequently reduced in response to glucocorticoids. This decline could therefore trigger Muscle Atrophy in catabolic conditions. Indeed, systemic administration of IGF-I prevents glucocorticoid-induced Muscle Atrophy. However, use of systemic IGF-I administration is limited by its hypoglycemic and cardiac hypertrophic actions. Moreover, local IGF-I seems to play a more important role in the regulation of Muscle mass than systemic IGF-I. Therefore, to limit loss of Muscle mass observed in catabolic states, IGF-I administration must mimic as close as possible the autocrine production of IGF-I. The aim of this thesis was to investigate whether the restoration of IGF-I Muscle content could reverse Muscle Atrophy induced by glucocorticoids. In this work we have tested the hypothesis that the local decrease in Muscle IGF-I content might be responsible for the muscular Atrophy induced by glucocorticoids. In our work, we have demonstrated that localized overexpression of IGF-I by gene electrotransfer prevents Muscle Atrophy in glucocorticoid-treated rats. High rate of fiber transfection and long term gene expression were obtained by combining multiple injection sites of DNA with electroporation. Human IGF-I gene electrotransfer using this optimised protocol resulted in increased Muscle IGF-I mRNA and protein levels together with prevention of loss of skeletal Muscle mass. Furthermore, alterations in the Akt/GSK-3â/â-catenin signaling pathway caused by glucocorticoids were prevented by local IGF-I gene overexpression. Finally, Muscle overexpression of caAkt, dnGSK-3b and ANb-catenin was sufficient to mimic the anti-atrophic effect of IGF-I supporting the role of this signalling pathway in Muscle Atrophy caused by glucocorticoids. Taken together, our results show, for the first time in vivo, the role of the IGF-I/Akt/GSK-3b/b-catenin pathway in the skeletal Muscle Atrophy caused by glucocorticoids. In conclusion, our work highlights the crucial role of decreased Muscle IGF-I in glucocorticoid-induced Muscle Atrophy. Indeed, the data presented in this thesis support the fact that the atrophic action of glucocorticoids is in part due to the downregulation of IGF-I, leading to the inhibition of its signalling pathways while restoration of Muscle IGF-I levels is able to counteract totally Muscle Atrophy.
Yong Soo Choi - One of the best experts on this subject based on the ideXlab platform.
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Umbilical cord mesenchymal stem cell-conditioned media prevent Muscle Atrophy by suppressing Muscle Atrophy-related proteins and ROS generation
In Vitro Cellular and Developmental Biology - Animal, 2016Co-Authors: Chan Mi Park, Z. Hun Kim, Sun Mi Kim, Mi Jin Kim, Jin Ho Park, Yong Soo ChoiAbstract:The therapeutic potential of mesenchymal stem cell-conditioned medium (MSC-CM) has been reported with various types of disease models. Here, we examine the therapeutic effect of umbilical cord MSC-CM (UCMSC-CM) on Muscle-related disease, using a dexamethasone (Dex)-induced Muscle Atrophy in vitro model. The expressions of Muscle Atrophy-related proteins (MuRF-1 and MAFbx) and Muscle-specific proteins (desmin and myogenin) were evaluated by Western blot analysis. The level of production of reactive oxygen species (ROS) was determined using a 2',7'-dichlorofluorescein diacetate (DCFDA) dye assay. The expression of antioxidant enzymes (copper/zinc-superoxide dismutase (Cu/Zn-SOD), manganese superoxide dismutase (MnSOD), glutathione peroxidase-1 (GPx-1), and catalase (CAT)) was verified by reverse transcription polymerase chain reaction (RT-PCR). When L6 cells were exposed to Dex, the expression of Muscle Atrophy-related proteins was increased by 50-70{% and the expression of Muscle-specific proteins was in turn decreased by 23-40{%}. Conversely, when the L6 cells were co-treated with UCMSC-CM and Dex, the expression of Muscle Atrophy-related proteins was reduced in a UCMSC-CM dose-dependent manner and the expression of Muscle-specific proteins was restored to near-normal levels. Moreover, ROS generation was effectively suppressed and the expression of antioxidant enzymes was recovered to a normal degree. These data imply that UCMSC-CM clearly has the potential to prevent Muscle Atrophy. Thus, our present study offers fundamental data on the potential treatment of Muscle-related disease using UCMSC-CM.}, keywords={*Mesenchymal Stem Cell Transplantation; Animals; Catalase/biosynthesis; Cell Proliferation/genetics; Culture Media; Conditioned/pharmacology; Desmin/*biosynthesis/genetics; Dexamethasone; Dexamethasone/toxicity; Disease Models; Animal; Gene Expression Regulation; Developmental/drug effects; Glutathione Peroxidase/biosynthesis; Humans; L6 skeletal Muscle cell; Mesenchymal Stromal Cells/cytology/drug effects; Muscle Proteins/biosynthesis/genetics; Muscle Atrophy; Muscular Atrophy/chemically induced/genetics/pathology/*therapy; Myogenin/*biosynthesis/genetics; Rats; Reactive Oxygen Species/*metabolism; SKP Cullin F-Box Protein Ligases/biosynthesis/genetics; Superoxide Dismutase/biosynthesis; Tripartite Motif Proteins; Ubiquitin-Protein Ligases/biosynthesis/genetics; Umbilical Cord/cytology/drug effects/transplantation; Umbilical cord mesenchymal stem cell (UCMSC); Umbilical cord mesenchymal stem cell-conditioned medium (UCMSC-CM)}, isbn={1071-2690}, language={eng}, url={https://link.springer.com/article/10.1007{%}2Fs11626-015-9948-1}, doi={10.1007/s11626-015-9948-1}
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Umbilical cord mesenchymal stem cell-conditioned media prevent Muscle Atrophy by suppressing Muscle Atrophy-related proteins and ROS generation
In Vitro Cellular & Developmental Biology – Animal, 2015Co-Authors: Chan Mi Park, Jin Ho Park, Yong Soo ChoiAbstract:The therapeutic potential of mesenchymal stem cell-conditioned medium (MSC-CM) has been reported with various types of disease models. Here, we examine the therapeutic effect of umbilical cord MSC-CM (UCMSC-CM) on Muscle-related disease, using a dexamethasone (Dex)-induced Muscle Atrophy in vitro model. The expressions of Muscle Atrophy-related proteins (MuRF-1 and MAFbx) and Muscle-specific proteins (desmin and myogenin) were evaluated by Western blot analysis. The level of production of reactive oxygen species (ROS) was determined using a 2′,7′-dichlorofluorescein diacetate (DCFDA) dye assay. The expression of antioxidant enzymes (copper/zinc-superoxide dismutase (Cu/Zn-SOD), manganese superoxide dismutase (MnSOD), glutathione peroxidase-1 (GPx-1), and catalase (CAT)) was verified by reverse transcription polymerase chain reaction (RT-PCR). When L6 cells were exposed to Dex, the expression of Muscle Atrophy-related proteins was increased by 50–70%, and the expression of Muscle-specific proteins was in turn decreased by 23–40%. Conversely, when the L6 cells were co-treated with UCMSC-CM and Dex, the expression of Muscle Atrophy-related proteins was reduced in a UCMSC-CM dose-dependent manner and the expression of Muscle-specific proteins was restored to near-normal levels. Moreover, ROS generation was effectively suppressed and the expression of antioxidant enzymes was recovered to a normal degree. These data imply that UCMSC-CM clearly has the potential to prevent Muscle Atrophy. Thus, our present study offers fundamental data on the potential treatment of Muscle-related disease using UCMSC-CM.
Andreas N Kavazis - One of the best experts on this subject based on the ideXlab platform.
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mitochondrial targeted antioxidants protect skeletal Muscle against immobilization induced Muscle Atrophy
Journal of Applied Physiology, 2011Co-Authors: Ashley J Smuder, Andreas N Kavazis, Oh Sung Kwon, Hazel H Szeto, Scott K PowersAbstract:Prolonged periods of muscular inactivity (e.g., limb immobilization) result in skeletal Muscle Atrophy. Although it is established that reactive oxygen species (ROS) play a role in inactivity-induced skeletal Muscle Atrophy, the cellular pathway(s) responsible for inactivity-induced ROS production remain(s) unclear. To investigate this important issue, we tested the hypothesis that elevated mitochondrial ROS production contributes to immobilization-induced increases in oxidative stress, protease activation, and myofiber Atrophy in skeletal Muscle. Cause-and-effect was determined by administration of a novel mitochondrial-targeted antioxidant (SS-31) to prevent immobilization-induced mitochondrial ROS production in skeletal Muscle fibers. Compared with ambulatory controls, 14 days of Muscle immobilization resulted in significant Muscle Atrophy, along with increased mitochondrial ROS production, Muscle oxidative damage, and protease activation. Importantly, treatment with a mitochondrial-targeted antioxidant attenuated the inactivity-induced increase in mitochondrial ROS production and prevented oxidative stress, protease activation, and myofiber Atrophy. These results support the hypothesis that redox disturbances contribute to immobilization-induced skeletal Muscle Atrophy and that mitochondria are an important source of ROS production in Muscle fibers during prolonged periods of inactivity.
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oxidative stress and disuse Muscle Atrophy
Journal of Applied Physiology, 2007Co-Authors: Scott K Powers, Andreas N Kavazis, Joseph M McclungAbstract:Skeletal Muscle inactivity is associated with a loss of Muscle protein and reduced force-generating capacity. This disuse-induced Muscle Atrophy results from both increased proteolysis and decrease...
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mechanisms of disuse Muscle Atrophy role of oxidative stress
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2005Co-Authors: Scott K Powers, Andreas N Kavazis, Keith C DeruisseauAbstract:Prolonged periods of skeletal Muscle inactivity lead to a loss of Muscle protein and strength. Advances in cell biology have progressed our understanding of those factors that contribute to Muscle Atrophy. To this end, abundant evidence implicates oxidative stress as a potential regulator of proteolytic pathways leading to Muscle Atrophy during periods of prolonged disuse. This review will address the role of reactive oxygen species and oxidative stress as potential contributors to the process of disuse-mediated Muscle Atrophy. The first section of this article will discuss our current understanding of Muscle proteases, sources of reactive oxygen in Muscle fibers, and the evidence linking oxidative stress to disuse Muscle Atrophy. The second section of this review will highlight gaps in our knowledge relative to the specific role of oxidative stress in the regulation of disuse Muscle Atrophy. By discussing unresolved issues and suggesting topics for future research, it is hoped that this review will serve as a stimulus for the expansion of knowledge in this exciting field.
