Protective effects of endurance exercise on skeletal muscle remodeling against doxorubicin-induced myotoxicity in mice

Skeletal muscle uses calcium as a second messenger to respond and adapt to environmental stimuli. Elevations in intracellular calcium levels activate calcineurin, a serine/threonine phosphatase, resulting in the expression of a set of genes involved in the maintenance, growth, and remodeling of skeletal muscle. In this review, we discuss the effects of calcineurin activity on hypertrophy, regeneration, and disorders of skeletal muscle. Calcineurin is a potent regulator of muscle remodeling, enhancing the differentiation through upregulation of myogenin or MEF2A and downregulation of the Id1 family and myostatin. Foxo may also be a downstream candidate for a calcineurin signaling molecule during muscle regeneration. The strategy of controlling the amount of calcineurin may be effective for the treatment of muscular disorders such as DMD, UCMD, and LGMD. Activation of calcineurin produces muscular hypertrophy of the slow-twitch soleus muscle but not fast-twitch muscles.

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SAT0464 Metabolic Effects in Skeletal Muscle of Endurance Exercise in Patients with Polymyositis and Dermatomyositis: A Pilot Study

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2015-eular.2420 ◽

2015 ◽

Vol 74 (Suppl 2) ◽

pp. 828.2-828 ◽

Cited By ~ 1

Author(s):

L. Alemo Munters ◽

M. Dastmalchi ◽

E. Lindroos ◽

C. Ottosson ◽

H. Alexanderson ◽

...

Keyword(s):

Skeletal Muscle ◽

Pilot Study ◽

Endurance Exercise ◽

Metabolic Effects

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Skeletal muscle biochemical adaptations to exercise training in miniature swine

Journal of Applied Physiology ◽

10.1152/jappl.1997.82.6.1862 ◽

1997 ◽

Vol 82 (6) ◽

pp. 1862-1868 ◽

Cited By ~ 23

Author(s):

Richard M. McAllister ◽

Brian L. Reiter ◽

John F. Amann ◽

M. Harold Laughlin

Keyword(s):

Skeletal Muscle ◽

Antioxidant Enzymes ◽

Lactate Dehydrogenase ◽

Exercise Training ◽

Endurance Exercise ◽

Oxidative Capacity ◽

Treadmill Running ◽

Miniature Swine ◽

Endurance Exercise Training ◽

Hydroxyacyl Coa Dehydrogenase

McAllister, Richard M., Brian L. Reiter, John F. Amann, and M. Harold Laughlin. Skeletal muscle biochemical adaptations to exercise training in miniature swine. J. Appl. Physiol. 82(6): 1862–1868, 1997.—The primary purpose of this study was to test the hypothesis that endurance exercise training induces increased oxidative capacity in porcine skeletal muscle. To test this hypothesis, female miniature swine were either trained by treadmill running 5 days/wk over 16–20 wk (Trn; n = 35) or pen confined (Sed; n = 33). Myocardial hypertrophy, lower heart rates during submaximal stages of a maximal treadmill running test, and increased running time to exhaustion during that test were indicative of training efficacy. A variety of skeletal muscles were sampled and subsequently assayed for the enzymes citrate synthase (CS), 3-hydroxyacyl-CoA dehydrogenase, and lactate dehydrogenase and for antioxidant enzymes. Fiber type composition of a representative muscle was also determined histochemically. The largest increase in CS activity (62%) was found in the gluteus maximus muscle (Sed, 14.7 ± 1.1 μmol ⋅ min−1 ⋅ g−1; Trn, 23.9 ± 1.0; P < 0.0005). Muscles exhibiting increased CS activity, however, were located primarily in the forelimb; ankle and knee extensor and respiratory muscles were unchanged with training. Only two muscles exhibited higher 3-hydroxyacyl-CoA dehydrogenase activity in Trn compared with Sed. Lactate dehydrogenase activity was unchanged with training, as were activities of antioxidant enzymes. Histochemical analysis of the triceps brachii muscle (long head) revealed lower type IIB fiber numbers in Trn (Sed, 42 ± 6%; Trn, 10 ± 4; P < 0.01) and greater type IID/X fiber numbers (Sed, 11 ± 2; Trn, 22 ± 3; P < 0.025). These findings indicate that porcine skeletal muscle adapts to endurance exercise training in a manner similar to muscle of humans and other animal models, with increased oxidative capacity. Specific muscles exhibiting these adaptations, however, differ between the miniature swine and other species.

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Skeletal muscle mitochondrial protein synthesis and respiration in response to the energetic stress of an ultra-endurance race

Journal of Applied Physiology ◽

10.1152/japplphysiol.00457.2017 ◽

2017 ◽

Vol 123 (6) ◽

pp. 1516-1524 ◽

Cited By ~ 6

Author(s):

Adam R. Konopka ◽

William M. Castor ◽

Christopher A. Wolff ◽

Robert V. Musci ◽

Justin J. Reid ◽

...

Keyword(s):

Skeletal Muscle ◽

Protein Synthesis ◽

Endurance Exercise ◽

Mitochondrial Respiration ◽

Endurance Athlete ◽

Control Period ◽

Mitochondrial Protein ◽

Mitochondrial Bioenergetics ◽

Mitochondrial Protein Synthesis ◽

Ultra Endurance

The 2016 Colorado Trail Race (CTR) was an ultra-endurance mountain bike race in which competitors cycled for up to 24 h/day between altitudes of 1,675 and 4,025 m to complete 800 km and 21,000 m of elevation gain. In one athlete, we had the unique opportunity to characterize skeletal muscle protein synthesis and mitochondrial respiration in response to a normal activity control period (CON) and the CTR. We hypothesized that mitochondrial protein synthesis would be elevated and mitochondrial respiration would be maintained during the extreme stresses of the CTR. Titrated and bolus doses of ADP were provided to determine substrate-specific oxidative phosphorylation (OXPHOS) and electron transport system (ETS) capacities in permeabilized muscle fibers via high-resolution respirometry. Protein synthetic rates were determined by daily oral consumption of deuterium oxide (2H2O). The endurance athlete had OXPHOS (226 pmol·s−1·mg tissue−1) and ETS (231 pmol·s−1·mg tissue−1) capacities that rank among the highest published to date in humans. Mitochondrial (3.2-fold), cytoplasmic (2.3-fold), and myofibrillar (1.5-fold) protein synthesis rates were greater during CTR compared with CON. With titrated ADP doses, the apparent Km of ADP, OXPHOS, and ETS increased after the CTR. With provision of ADP boluses after the CTR, the addition of fatty acids (−12 and −14%) mitigated the decline in OXPHOS and ETS capacity during carbohydrate-supported respiration (−26 and −31%). In the face of extreme stresses during the CTR, elevated rates of mitochondrial protein synthesis may contribute to rapid adaptations in mitochondrial bioenergetics. NEW & NOTEWORTHY The mechanisms that maintain skeletal muscle function during extreme stresses remain incompletely understood. In the current study, greater rates of mitochondrial protein synthesis during the energetic demands of ultra-endurance exercise may contribute to rapid adaptations in mitochondrial bioenergetics. The endurance athlete herein achieved mitochondrial respiratory capacities among the highest published for humans. Greater mitochondrial protein synthesis during ultra-endurance exercise may contribute to improved mitochondrial respiration and serve as a mechanism to resist cellular energetic stresses.

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Effects of Endurance Exercise and High-Fat Diet on Insulin Resistance and Ceramide Contents of Skeletal Muscle in Sprague-Dawley Rats

Korean Diabetes Journal ◽

10.4093/kdj.2010.34.4.244 ◽

2010 ◽

Vol 34 (4) ◽

pp. 244 ◽

Cited By ~ 9

Author(s):

Hyun Lyung Jung ◽

Ho Youl Kang

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Endurance Exercise ◽

High Fat Diet ◽

Sprague Dawley ◽

High Fat ◽

Sprague Dawley Rats

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Upregulation of Heme Oxygenase-1 by Hemin Alleviates Sepsis-Induced Muscle Wasting in Mice

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/8927104 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

Xiongwei Yu ◽

Wenjun Han ◽

Changli Wang ◽

Daming Sui ◽

Jinjun Bian ◽

...

Keyword(s):

Skeletal Muscle ◽

Heme Oxygenase ◽

Muscle Atrophy ◽

Muscle Wasting ◽

Cecal Ligation ◽

Skeletal Muscle Atrophy ◽

Enzyme Linked Immunosorbent Assay ◽

Heme Oxygenase 1 ◽

Protective Effects ◽

Sod Activity

Hemin, an inducer of heme oxygenase-1 (HO-1), can enhance the activation of HO-1. HO-1 exhibits a variety of activities, such as anti-inflammatory, antioxidative, and antiapoptotic functions. The objective of this study was to investigate the effects of hemin on sepsis-induced skeletal muscle wasting and to explore the mechanisms by which hemin exerts its effects. Cecal ligation and perforation (CLP) was performed to create a sepsis mouse model. Mice were randomly divided into four groups: control, CLP, CLP plus group, and CLP-hemin-ZnPP (a HO-1 inhibitor). The weight of the solei from the mice was measured, and histopathology was examined. Cytokines were measured by enzyme-linked immunosorbent assay (ELISA). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting were used to assess the expression levels of HO-1 and atrogin-1. Furthermore, we investigated the antioxidative effects of HO-1 by detecting malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity. CLP led to dramatic skeletal muscle weakness and atrophy, but pretreatment with hemin protected mice against CLP-mediated muscle atrophy. Hemin also induced high HO-1 expression, which resulted in suppressed proinflammatory cytokine and reactive oxygen species (ROS) production. The expression of MuRF1 and atrogin-1, two ubiquitin ligases of the ubiquitin-proteasome system- (UPS-) mediated proteolysis, was also inhibited by increased HO-1 levels. Hemin-mediated increases in HO-1 expression exert protective effects on sepsis-induced skeletal muscle atrophy at least partly by inhibiting the expression of proinflammatory cytokines, UPS-mediated proteolysis, and ROS activation. Therefore, hemin might be a new treatment target against sepsis-induced skeletal muscle atrophy.

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