Angiotensin 1‐7 reduces muscle atrophy and function loss following 16 week denervation

Oculopharyngeal muscular dystrophy (OPMD) is a late-onset disorder characterized by progressive weakness and degeneration of specific muscles. OPMD is due to extension of a polyalanine tract in poly(A) binding protein nuclear 1 (PABPN1). Aggregation of the mutant protein in muscle nuclei is a hallmark of the disease. Previous transcriptomic analyses revealed the consistent deregulation of the ubiquitin-proteasome system (UPS) in OPMD animal models and patients, suggesting a role of this deregulation in OPMD pathogenesis. Subsequent studies proposed that UPS contribution to OPMD involved PABPN1 aggregation. Here, we use a Drosophila model of OPMD to address the functional importance of UPS deregulation in OPMD. Through genome-wide and targeted genetic screens we identify a large number of UPS components that are involved in OPMD. Half dosage of UPS genes reduces OPMD muscle defects suggesting a pathological increase of UPS activity in the disease. Quantification of proteasome activity confirms stronger activity in OPMD muscles, associated with degradation of myofibrillar proteins. Importantly, improvement of muscle structure and function in the presence of UPS mutants does not correlate with the levels of PABPN1 aggregation, but is linked to decreased degradation of muscle proteins. Oral treatment with the proteasome inhibitor MG132 is beneficial to the OPMD Drosophila model, improving muscle function although PABPN1 aggregation is enhanced. This functional study reveals the importance of increased UPS activity that underlies muscle atrophy in OPMD. It also provides a proof-of-concept that inhibitors of proteasome activity might be an attractive pharmacological approach for OPMD.

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Modelling functional differentiation and function loss

Papers from the 5th International Conference on English Historical Linguistics - Current Issues in Linguistic Theory ◽

10.1075/cilt.65.20nev ◽

1990 ◽

pp. 337 ◽

Cited By ~ 1

Author(s):

Terttu Nevalainen

Keyword(s):

Functional Differentiation ◽

Function Loss ◽

And Function

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Effect of vagus nerve stimulation on tissue damage and function loss in a mouse myocardial ischemia-reperfusion model

Autonomic Neuroscience ◽

10.1016/j.autneu.2019.102580 ◽

2019 ◽

Vol 221 ◽

pp. 102580 ◽

Cited By ~ 1

Author(s):

M.G.J. Nederhoff ◽

D.E. Fransen ◽

S.A.M.W. Verlinde ◽

M.A.D. Brans ◽

G. Pasterkamp ◽

...

Keyword(s):

Myocardial Ischemia ◽

Vagus Nerve ◽

Nerve Stimulation ◽

Tissue Damage ◽

Vagus Nerve Stimulation ◽

Ischemia Reperfusion ◽

Function Loss ◽

Myocardial Ischemia Reperfusion ◽

And Function

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Relationship of Skeletal Muscle Atrophy to Functional Status: A Systematic Research Review

Biological Research For Nursing ◽

10.1177/109980040000200205 ◽

2000 ◽

Vol 2 (2) ◽

pp. 117-131 ◽

Cited By ~ 9

Author(s):

Kathleen Michael

Keyword(s):

Muscle Atrophy ◽

Elderly Women ◽

Functional Limitation ◽

Skeletal Muscle Atrophy ◽

Research Review ◽

Systematic Research ◽

Form And Function ◽

And Function ◽

Relationship Of ◽

The Relationship

In the realm of muscle atrophy research, many studies address minute details of molecular function but few examine the effects of atrophy in terms of mobility, strength, endurance, and performance of activities of daily living. The relationship between impairment and functional limitation is the focus of this research review. A wide array of studies constitute this area of inquiry, including investigations as diverse and widely disparate as molecular chemistry and space travel and populations as different as rats, healthy young men, and elderly women. Thirty-four studies were selected based on their fit with the Enabling-Disabling Model. Three paradigms of atrophy and function emerged. Adaptation reflects the plastic nature of muscle when placed under certain conditions, ranging from disuse to high-resistance exercise. Injury/loss describes damage to muscle tissue from ischemia, medications, or reloading or reperfusion trauma. Also in this category is the loss of muscle that is seen with aging. Integrity relates to the muscle’s tendency to protect itself and maintain structural adjacencies and cellular proportions. Based on the 3 muscle research paradigms, the relationship of muscle atrophy to function is portrayed as a bidirectional interaction wherein form and function have an influence on each other by way of physical changes, including those of adaptation, injury/loss, or integrity. A conceptual model is constructed to reflect this relationship.

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Two Weeks of Smoking Cessation Reverse Cigarette Smoke-Induced Skeletal Muscle Atrophy and Mitochondrial Dysfunction in Mice

Nicotine & Tobacco Research ◽

10.1093/ntr/ntaa016 ◽

2020 ◽

Cited By ~ 2

Author(s):

Tom Tanjeko Ajime ◽

Jef Serré ◽

Rob C I Wüst ◽

Guy Anselme Mpaka Messa ◽

Chiel Poffé ◽

...

Keyword(s):

Skeletal Muscle ◽

Smoking Cessation ◽

Mitochondrial Dysfunction ◽

Muscle Mass ◽

Muscle Atrophy ◽

Skeletal Muscles ◽

Skeletal Muscle Atrophy ◽

Limb Muscle ◽

Male Mice ◽

And Function

Abstract Introduction Apart from its adverse effects on the respiratory system, cigarette smoking also induces skeletal muscle atrophy and dysfunction. Whether short-term smoking cessation can restore muscle mass and function is unknown. We, therefore, studied the impact of 1- and 2-week smoking cessation on skeletal muscles in a mouse model. Methods Male mice were divided into four groups: Air-exposed (14 weeks); cigarette smoke (CS)-exposed (14 weeks); CS-exposed (13 weeks) followed by 1-week cessation; CS-exposed (12 weeks) followed by 2 weeks cessation to examine exercise capacity, physical activity levels, body composition, muscle function, capillarization, mitochondrial function and protein expression in the soleus, plantaris, and diaphragm muscles. Results CS-induced loss of body and muscle mass was significantly improved within 1 week of cessation due to increased lean and fat mass. Mitochondrial respiration and protein levels of the respiratory complexes in the soleus were lower in CS-exposed mice, but similar to control values after 2 weeks of cessation. Exposing isolated soleus muscles to CS extracts reduced mitochondrial respiration that was reversed after removing the extract. While physical activity was reduced in all groups, exercise capacity, limb muscle force, fatigue resistance, fiber size and capillarization, and diaphragm cytoplasmic HIF-1α were unaltered by CS-exposure. However, CS-induced diaphragm atrophy and increased capillary density were not seen after 2 weeks of smoking cessation. Conclusion In male mice, 2 weeks of smoking cessation reversed smoking-induced mitochondrial dysfunction, limb muscle mass loss, and diaphragm muscle atrophy, highlighting immediate benefits of cessation on skeletal muscles. Implications Our study demonstrates that CS-induced skeletal muscle mitochondrial dysfunction and atrophy are significantly improved by 2 weeks of cessation in male mice. We show for the first time that smoking cessation as short as 1 to 2 weeks is associated with immediate beneficial effects on skeletal muscle structure and function with the diaphragm being particularly sensitive to CS-exposure and cessation. This could help motivate smokers to quit smoking as early as possible. The knowledge that smoking cessation has potential positive extrapulmonary effects is particularly relevant for patients referred to rehabilitation programs and those admitted to hospitals suffering from acute or chronic muscle deterioration yet struggling with smoking cessation.

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Exercise preconditioning diminishes skeletal muscle atrophy after hindlimb suspension in mice

Journal of Applied Physiology ◽

10.1152/japplphysiol.00137.2018 ◽

2018 ◽

Vol 125 (4) ◽

pp. 999-1010 ◽

Cited By ~ 7

Author(s):

Nicholas T. Theilen ◽

Nevena Jeremic ◽

Gregory J. Weber ◽

Suresh C. Tyagi

Keyword(s):

Skeletal Muscle ◽

Exercise Training ◽

Muscle Atrophy ◽

Mitochondrial Biogenesis ◽

Weight Ratio ◽

Hindlimb Suspension ◽

Skeletal Muscle Atrophy ◽

Short Term ◽

Concurrent Exercise ◽

And Function

The aim of the present study was to investigate whether short-term, concurrent exercise training before hindlimb suspension (HLS) prevents or diminishes both soleus and gastrocnemius atrophy and to analyze whether changes in mitochondrial molecular markers were associated. Male C57BL/6 mice were assigned to control at 13 ± 1 wk of age, 7-day HLS at 12 ± 1 wk of age (HLS), 2 wk of exercise training before 7-day HLS at 10 ± 1 wk of age (Ex+HLS), and 2 wk of exercise training at 11 ± 1 wk of age (Ex) groups. HLS resulted in a 27.1% and 21.5% decrease in soleus and gastrocnemius muscle weight-to-body weight ratio, respectively. Exercise training before HLS resulted in a 5.6% and 8.1% decrease in soleus and gastrocnemius weight-to-body weight ratio, respectively. Exercise increased mitochondrial biogenesis- and function-associated markers and slow myosin heavy chain (SMHC) expression, and reduced fiber-type transitioning marker myosin heavy chain 4 (Myh4). Ex+HLS revealed decreased reactive oxygen species (ROS) and oxidative stress compared with HLS. Our data indicated the time before an atrophic setting, particularly caused by muscle unloading, may be a useful period to intervene short-term, progressive exercise training to prevent skeletal muscle atrophy and is associated with mitochondrial biogenesis, function, and redox balance. NEW & NOTEWORTHY Mitochondrial dysfunction is associated with disuse-induced skeletal muscle atrophy, whereas exercise is known to increase mitochondrial biogenesis and function. Here we provide evidence of short-term concurrent exercise training before an atrophic event protecting skeletal muscle from atrophy in two separate muscles with different, dominant fiber-types, and we reveal an association with the adaptive changes of mitochondrial molecular markers to exercise.

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