scholarly journals Role of Akt/GSK-3β/β-Catenin Transduction Pathway in the Muscle Anti-Atrophy Action of Insulin-Like Growth Factor-I in Glucocorticoid-Treated Rats

Endocrinology ◽  
2008 ◽  
Vol 149 (8) ◽  
pp. 3900-3908 ◽  
Author(s):  
O. Schakman ◽  
S. Kalista ◽  
L. Bertrand ◽  
P. Lause ◽  
J. Verniers ◽  
...  
Keyword(s):  
Muscle Atrophy ◽  
Critical Role ◽  
Cross Sectional Area ◽  
Stable Form ◽  
Transduction Pathway ◽  
Sectional Area ◽  
Cross Sectional ◽  
Igf I ◽  
Gsk 3Β ◽  
Intracellular Mediators

Decrease of muscle IGF-I plays a critical role in muscle atrophy caused by glucocorticoids (GCs) because IGF-I gene electrotransfer prevents muscle atrophy caused by GCs. The goal of the present study was to identify the intracellular mediators responsible for the IGF-I anti-atrophic action in GC-induced muscle atrophy. We first assessed the IGF-I transduction pathway alterations caused by GC administration and their reversibility by local IGF-I overexpression performed by electrotransfer. Muscle atrophy induced by dexamethasone (dexa) administration occurred with a decrease in Akt (−53%; P <0.01) phosphorylation together with a decrease in β-catenin protein levels (−40%; P <0.001). Prevention of atrophy by IGF-I was associated with restoration of Akt phosphorylation and β-catenin levels. We then investigated whether muscle overexpression of these intracellular mediators could mimic the IGF-I anti-atrophic effects. Overexpression of a constitutively active form of Akt induced a marked fiber hypertrophy in dexa-treated animals (+175% of cross-sectional area; P <0.001) and prevented dexa-induced atrophy. This hypertrophy was associated with an increase in phosphorylated GSK-3β (+17%; P <0.05) and in β-catenin content (+35%; P <0.05). Furthermore, overexpression of a dominant-negative GSK-3β or a stable form of β-catenin increased fiber cross-sectional area by, respectively, 23% (P <0.001) and 29% (P <0.001) in dexa-treated rats, preventing completely the atrophic effect of GC. In conclusion, this work indicates that Akt, GSK-3β, and β-catenin probably contribute together to the IGF-I anti-atrophic effect in GC-induced muscle atrophy.

scholarly journals Atrophy patterns in isolated subscapularis lesions

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Gernot Seppel ◽  
Andreas Voss ◽  
Daniel J. H. Henderson ◽  
Simone Waldt ◽  
Bernhard Haller ◽  
...  
Keyword(s):  
Muscle Atrophy ◽  
Area Ratio ◽  
Cross Sectional Area ◽  
Control Group ◽  
Sectional Area ◽  
Cross Sectional ◽  
Subscapularis Muscle ◽  
Mri Scans ◽  
The Mean ◽  
The Cross

Abstract Background While supraspinatus atrophy can be described according to the system of Zanetti or Thomazeau there is still a lack of characterization of isolated subscapularis muscle atrophy. The aim of this study was to describe patterns of muscle atrophy following repair of isolated subscapularis (SSC) tendon. Methods Forty-nine control shoulder MRI scans, without rotator cuff pathology, atrophy or fatty infiltration, were prospectively evaluated and subscapularis diameters as well as cross sectional areas (complete and upper half) were assessed in a standardized oblique sagittal plane. Calculation of the ratio between the upper half of the cross sectional area (CSA) and the total CSA was performed. Eleven MRI scans of patients with subscapularis atrophy following isolated subscapularis tendon tears were analysed and cross sectional area ratio (upper half /total) determined. To guarantee reliable measurement of the CSA and its ratio, bony landmarks were also defined. All parameters were statistically compared for inter-rater reliability, reproducibility and capacity to quantify subscapularis atrophy. Results The mean age in the control group was 49.7 years (± 15.0). The mean cross sectional area (CSA) was 2367.0 mm2 (± 741.4) for the complete subscapularis muscle and 1048.2 mm2 (± 313.3) for the upper half, giving a mean ratio of 0.446 (± 0.046). In the subscapularis repair group the mean age was 56.7 years (± 9.3). With a mean cross sectional area of 1554.7 mm2 (± 419.9) for the complete and of 422.9 mm2 (± 173.6) for the upper half of the subscapularis muscle, giving a mean CSA ratio of 0.269 (± 0.065) which was seen to be significantly lower than that of the control group (p < 0.05). Conclusion Analysis of typical atrophy patterns of the subscapularis muscle demonstrates that the CSA ratio represents a reliable and reproducible assessment tool in quantifying subscapularis atrophy. We propose the classification of subscapularis atrophy as Stage I (mild atrophy) in case of reduction of the cross sectional area ratio < 0.4, Stage II (moderate atrophy) in case of < 0.35 and Stage III (severe atrophy) if < 0.3.

Maintenance of myonuclear domain size in rat soleus after overload and growth hormone/IGF-I treatment

1998 ◽  
Vol 84 (4) ◽  
pp. 1407-1412 ◽  
Author(s):  
G. E. McCall ◽  
D. L. Allen ◽  
J. K. Linderman ◽  
R. E. Grindeland ◽  
R. R. Roy ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Domain Size ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Muscle Weight ◽  
Cross Sectional ◽  
Igf I ◽  
Myonuclear Domain ◽  
The Difference ◽  
Saline Vehicle

The purpose of this study was to determine the effects of functional overload (FO) combined with growth hormone/insulin-like growth factor I (GH/IGF-I) administration on myonuclear number and domain size in rat soleus muscle fibers. Adult female rats underwent bilateral ablation of the plantaris and gastrocnemius muscles and, after 7 days of recovery, were injected three times daily for 14 days with GH/IGF-I (1 mg/kg each; FO + GH/IGF-I group) or saline vehicle (FO group). Intact rats receiving saline vehicle served as controls (Con group). Muscle wet weight was 32% greater in the FO than in the Con group: 162 ± 8 vs. 123 ± 16 mg. Muscle weight in the FO + GH/IGF-I group (196 ± 14 mg) was 59 and 21% larger than in the Con and FO groups, respectively. Mean soleus fiber cross-sectional area of the FO + GH/IGF-I group (2,826 ± 445 μm2) was increased compared with the Con (2,044 ± 108 μm2) and FO (2,267 ± 301 μm2) groups. The difference in fiber size between the FO and Con groups was not significant. Mean myonuclear number increased in FO (187 ± 15 myonuclei/mm) and FO + GH/IGF-I (217 ± 23 myonuclei/mm) rats compared with Con (155 ± 12 myonuclei/mm) rats, although the difference between FO and FO + GH/IGF-I animals was not significant. The mean cytoplasmic volume per myonucleus (myonuclear domain) was similar across groups. These results demonstrate that the larger mean muscle weight and fiber cross-sectional area occurred when FO was combined with GH/IGF-I administration and that myonuclear number increased concomitantly with fiber volume. Thus there appears to be some mechanism(s) that maintains the myonuclear domain when a fiber hypertrophies.

scholarly journals Inorganic Arsenic Exposure Decreases Muscle Mass and Enhances Denervation-Induced Muscle Atrophy in Mice

Molecules ◽  
2020 ◽  
Vol 25 (13) ◽  
pp. 3057
Author(s):  
Chang-Mu Chen ◽  
Min-Ni Chung ◽  
Chen-Yuan Chiu ◽  
Shing-Hwa Liu ◽  
Kuo-Cheng Lan
Keyword(s):  
Drinking Water ◽  
Protein Expression ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Arsenic Exposure ◽  
Inorganic Arsenic ◽  
Cross Sectional Area ◽  
Muscle Endurance ◽  
Sectional Area ◽  
Cross Sectional

Arsenic is a toxic metalloid. Infants with a low birth-weight have been observed in areas with high-level arsenic in drinking water ranging from 463 to 1025 μg/L. A distal muscular atrophy side effect has been observed in acute promyelocytic leukemia patients treated with arsenic trioxide (As2O3) for therapy. The potential of As2O3 on muscle atrophy remains to be clarified. In this study, the myoatrophic effect of arsenic was evaluated in normal mice and sciatic nerve denervated mice exposed with or without As2O3 (0.05 and 0.5 ppm) in drinking water for 4 weeks. We found that both 0.05 and 0.5 ppm As2O3 increased the fasting plasma glucose level; but only 0.5 ppm arsenic exposure significantly decreased muscle mass, muscle endurance, and cross-sectional area of muscle fibers, and increased muscle Atrogin-1 protein expression in the normal mice. Both 0.05 and 0.5 ppm As2O3 also significantly enhanced the inhibitory effects on muscle endurance, muscle mass, and cross-sectional area of muscle fibers, and increased the effect on muscle Atrogin-1 protein expression in the denervated mice. These in vivo results suggest that inorganic arsenic at doses relevant to humans may possess myoatrophic potential.

Microcirculatory structure-function relationships in skeletal muscle of diabetic rats

1994 ◽  
Vol 266 (4) ◽  
pp. H1502-H1511 ◽  
Author(s):  
W. L. Sexton ◽  
D. C. Poole ◽  
O. Mathieu-Costello
Keyword(s):  
Skeletal Muscle ◽  
Structure Function ◽  
Surface Area ◽  
Muscle Atrophy ◽  
Muscle Fiber ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Diffusing Capacity ◽  
Capillary Surface ◽  
Cross Sectional

The effects of streptozotocin-induced diabetes on microcirculatory structure-function relationships in skeletal muscle were studied in control (C) and diabetic (D; 65 mg/kg streptozotocin ip) rats 6-8 wk after injection. Capillary exchange capacity was determined from measurements of capillary filtration coefficient (CFC) and permeability-surface area product (PS) for 51Cr-labeled EDTA in maximally vasodilated (papaverine), isolated hindquarters of C (n = 9) and D (n = 12) rats. Capillary numerical density, length, surface area, capillary geometry, and muscle fiber cross-sectional area were determined using morphometric methods in perfusion-fixed plantaris muscles from a second series of C (n = 5) and D (n = 6) rats. Hindquarters of D rats (61 +/- 3 g) weighed less than C rats (90 +/- 3 g) because of marked muscle atrophy. Minimal total vascular resistance was lower in D rats (P < or = 0.05), indicating an increased flow capacity. CFC was not different in C and D rats (0.0282 +/- 0.0020 vs. 0.0330 +/- 0.0025 ml.min-1.mmHg-1 x 100 g-1, respectively). The relationship between PS and flow was depressed in D rats (P < or = 0.05) compared with C rats, which indicated a reduced capillary diffusing capacity. Plantaris muscle weight was 41% less in D rats (174 +/- 9 vs. 293 +/- 11 mg; P < or = 0.001). Morphometric analysis revealed that muscle fiber cross-sectional area was reduced 39% in D rats, which, despite a lower capillary-to-fiber ratio (1.59 +/- 0.04 vs. 2.12 +/- 0.13; P < or = 0.001), resulted in a 27% increase in capillary density in D rats. Capillary diameter was less in D rats (3.58 +/- 0.12 vs. 4.51 +/- 0.23 microns; P < or = 0.005). Total capillary surface area was reduced 42% in D rats; however, capillary surface area per muscle fiber volume was unchanged in D rats (231 +/- 34 vs. 237 +/- 16 cm-1). These data indicate that there is remodeling of the capillary bed in skeletal muscle of D rats, resulting in a reduction in total microvascular surface area. The reduction in capillary surface area is proportional to the degree of muscle atrophy in D rats such that functional microvascular surface area per tissue mass (e.g., CFC) is unchanged. The lower diffusing capacity (PS) in D rats suggests that either small solute permeability is reduced and/or there is greater perfusion heterogeneity in D rat skeletal muscle.

scholarly journals A transient antioxidant stress response accompanies the onset of disuse atrophy in human skeletal muscle

2009 ◽  
Vol 107 (2) ◽  
pp. 549-557 ◽  
Author(s):  
Luciano Dalla Libera ◽  
Barbara Ravara ◽  
Valerio Gobbo ◽  
Elena Tarricone ◽  
Maurizio Vitadello ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Stress Response ◽  
Muscle Atrophy ◽  
Cross Sectional Area ◽  
Heme Oxygenase 1 ◽  
Sectional Area ◽  
Cross Sectional ◽  
Protein Levels ◽  
Antioxidant Stress

It is presently unknown whether oxidative stress increases in disused skeletal muscle in humans. Markers of oxidative stress were investigated in biopsies from the vastus lateralis muscle, collected from healthy subjects before [ time 0 (T0)], after 1 wk (T8), and after 5 wk (T35) of bed rest. An 18% decrease in fiber cross-sectional area was detected in T35 biopsies ( P < 0.05). Carbonylation of muscle proteins significantly increased about twofold at T35 ( P < 0.02) and correlated positively with the decrease in fiber cross-sectional area ( P = 0.04). Conversely, T8 biopsies showed a significant increase in protein levels of heme oxygenase-1 and glucose-regulated protein-75 (Grp75)/mitochondrial heat shock protein-70, two stress proteins involved in the antioxidant defense ( P < 0.05). Heme oxygenase-1 increase, which involved a larger proportion of slow fibers compared with T0, appeared blunted in T35 biopsies. Grp75 protein level increased threefold in T8 biopsies and localized especially in slow fibers ( P < 0.025), to decrease significantly in T35 biopsies ( P < 0.05). Percent change in Grp75 levels positively correlated with fiber cross-sectional area ( P = 0.01). Parallel investigations on rat soleus muscles, performed after 1–15 days of hindlimb suspension, showed that Grp75 protein levels significantly increased after 24 h of unloading ( P = 0.02), i.e., before statistically significant evidence of muscle atrophy, to decrease thereafter in relation to the degree of muscle atrophy ( P = 0.03). Therefore, in humans as in rodents, disuse muscle atrophy is characterized by increased protein carbonylation and by the blunting of the antioxidant stress response evoked by disuse.

scholarly journals Overexpression of HSP10 in skeletal muscle of transgenic mice prevents the age-related fall in maximum tetanic force generation and muscle cross-sectional area

2010 ◽  
Vol 299 (1) ◽  
pp. R268-R276 ◽  
Author(s):  
Anna C. Kayani ◽  
Graeme L. Close ◽  
Wolfgang H. Dillmann ◽  
Ruben Mestril ◽  
Malcolm J. Jackson ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Cross Sectional Area ◽  
Force Generation ◽  
Sectional Area ◽  
Wild Type ◽  
Cross Sectional ◽  
Tetanic Force ◽  
Age Related ◽  
Muscle Cross Sectional Area

Skeletal muscle atrophy and weakness are major contributors to frailty and impact significantly on quality of life of older people. Muscle aging is characterized by a loss of maximum tetanic force (Po) generation, primarily due to muscle atrophy, to which mitochondrial dysfunction is hypothesized to contribute. We hypothesized that lifelong overexpression of the mitochondrial heat shock protein (HSP) HSP10 in muscle of mice would protect against development of these deficits. Po generation by extensor digitorum longus muscles of adult and old wild-type and HSP10-overexpressing mice was determined in situ. Muscles were subjected to damaging lengthening contractions, and force generation was remeasured at 3 h or 28 days to examine susceptibility to, and recovery from, damage, respectively. Muscles of old wild-type mice had a 23% deficit in Po generation and a 10% deficit in muscle cross-sectional area compared with muscles of adult wild-type mice. Overexpression of HSP10 prevented this age-related fall in Po generation and reduction in cross-sectional area observed in muscles of old wild-type mice. Additionally, overexpression of HSP10 protected against contraction-induced damage independent of age but did not improve recovery if damage occurred. Preservation of muscle force generation and CSA by HSP10 overexpression was associated with protection against the age-related accumulation of protein carbonyls. Data demonstrate that development of age-related muscle weakness may not be inevitable and show, for the first time, that lifelong overexpression of an HSP prevents the age-related loss of Po generation. These findings support the hypothesis that mitochondrial dysfunction is involved in the development of age-related muscle deficits.

NF-κB activation and polyubiquitin conjugation are required for pulmonary inflammation-induced diaphragm atrophy

2012 ◽  
Vol 302 (1) ◽  
pp. L103-L110 ◽  
Author(s):  
Astrid Haegens ◽  
Annemie M. Schols ◽  
Stefan H. Gorissen ◽  
Anon L. van Essen ◽  
Frank Snepvangers ◽  
...  
Keyword(s):  
Protein Degradation ◽  
Muscle Atrophy ◽  
Pulmonary Inflammation ◽  
Cross Sectional Area ◽  
26S Proteasome ◽  
Diaphragm Muscle ◽  
Chronic Obstructive ◽  
Sectional Area ◽  
Cross Sectional ◽  
Diaphragm Atrophy

Loss of diaphragm muscle strength in inflammatory lung disease contributes to mortality and is associated with diaphragm fiber atrophy. Ubiquitin (Ub) 26S-proteasome system (UPS)-dependent protein breakdown, which mediates muscle atrophy in a number of physiological and pathological conditions, is elevated in diaphragm muscle of patients with chronic obstructive pulmonary disease. Nuclear factor kappa B (NF-κB), an essential regulator of many inflammatory processes, has been implicated in the regulation of poly-Ub conjugation of muscle proteins targeted for proteolysis by the UPS. Here, we test if NF-κB activation in diaphragm muscle and subsequent protein degradation by the UPS are required for pulmonary inflammation-induced diaphragm atrophy. Acute pulmonary inflammation was induced in mice by intratracheal lipopolysaccharide instillation. Fiber cross-sectional area, ex vivo tyrosine release, protein poly-Ub conjugation, and inflammatory signaling were determined in diaphragm muscle. The contribution of NF-κB or the UPS to diaphragm atrophy was assessed in mice with intact or genetically repressed NF-κB signaling or attenuated poly-Ub conjugation, respectively. Acute pulmonary inflammation resulted in diaphragm atrophy measured by reduced muscle fiber cross-sectional area. This was accompanied by diaphragm NF-κB activation, and proteolysis, measured by tyrosine release from the diaphragm. Poly-Ub conjugation was increased in diaphragm, as was the expression of muscle-specific E3 Ub ligases. Genetic suppression of poly-Ub conjugation prevented inflammation-induced diaphragm muscle atrophy, as did muscle-specific inhibition of NF-κB signaling. In conclusion, the present study is the first to demonstrate that diaphragm muscle atrophy, resulting from acute pulmonary inflammation, requires NF-κB activation and UPS-mediated protein degradation.

scholarly journals Upper limb muscle atrophy associated with in-hospital mortality and physical function impairments in mechanically ventilated critically ill adults: a two-center prospective observational study

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Nobuto Nakanishi ◽  
Jun Oto ◽  
Rie Tsutsumi ◽  
Yusuke Akimoto ◽  
Yuki Nakano ◽  
...  
Keyword(s):  
Hospital Mortality ◽  
Physical Function ◽  
Muscle Atrophy ◽  
Upper Limb ◽  
Biceps Brachii ◽  
Cross Sectional Area ◽  
Apache Ii Score ◽  
Limb Muscle ◽  
Sectional Area ◽  
Cross Sectional

Abstract Background Lower limb muscle atrophy is often observed in critically ill patients. Although upper limb muscles can undergo atrophy, it remains unclear how this atrophy is associated with clinical outcomes. We hypothesized that this atrophy is associated with mortality and impairments in physical function. Methods In this two-center prospective observational study, we included adult patients who were expected to require mechanical ventilation for > 48 h and remain in the intensive care unit (ICU) for > 5 days. We used ultrasound to evaluate the cross-sectional area of the biceps brachii on days 1, 3, 5, and 7 and upon ICU discharge along with assessment of physical functions. The primary outcome was the relationship between muscle atrophy ratio and in-hospital mortality on each measurement day, which was assessed using multivariate analysis. The secondary outcomes were the relationships between upper limb muscle atrophy and Medical Research Council (MRC) score, handgrip strength, ICU Mobility Scale (IMS) score, and Functional Status Score for the ICU (FSS-ICU). Results Sixty-four patients (43 males; aged 70 ± 13 years) were enrolled. The Acute Physiology and Chronic Health Evaluation (APACHE) II score was 27 (22–30), and in-hospital mortality occurred in 21 (33%) patients. The decreased cross-sectional area of the biceps brachii was not associated with in-hospital mortality on day 3 (p = 0.43) but was associated on days 5 (p = 0.01) and 7 (p < 0.01), which was confirmed after adjusting for sex, age, and APACHE II score. In 27 patients in whom physical functions were assessed, the decrease of the cross-sectional area of the biceps brachii was associated with MRC score (r = 0.47, p = 0.01), handgrip strength (r = 0.50, p = 0.01), and FSS-ICU (r = 0.56, p < 0.01), but not with IMS score (r = 0.35, p = 0.07) upon ICU discharge. Conclusions Upper limb muscle atrophy was associated with in-hospital mortality and physical function impairments; thus, it is prudent to monitor it. (321 words) Trial registration UMIN 000031316. Retrospectively registered on 15 February 2018.

scholarly journals Estrogen treatment effects on rats soleus muscles' glycogen content, extracellular matrix and cross-sectional area

2017 ◽  
Vol 34 (04) ◽  
pp. 257-261
Author(s):  
M. Severi ◽  
J. Durigan ◽  
E. Pereira ◽  
L. Batista e Silva ◽  
W. Martins ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Muscle Glycogen ◽  
Glycogen Content ◽  
Cross Sectional Area ◽  
Estrogen Treatment ◽  
Sectional Area ◽  
Cross Sectional ◽  
Tissue Density

Abstract Objective: To evaluate the effects of estrogen treatment of rats' soleus muscles after denervation on glucose metabolism, muscle mass, glycogen content, cross-sectional area and connective tissue density. Methods: Eighteen rats were divided into the following three groups of six animals: control, denervated for 7 days (denervated), and denervated with estradiol treatment for 7 days (denervated and treated). We measured glucose and insulin tolerance, muscle glycogen, mass, cross-sectional area and connective tissue content. Results: The denervated only and the denervated and treated groups displayed a significant reduction in glucose uptake (32% and 53% respectively compared with the control group; p<0.05). Soleus muscle denervation reduced muscle glycogen (0.25 ± 0.03 vs 0.43 ± 0.02 mg/100mg; p<0.05), muscle mass (0.33 ± 0.09 vs. 0.48 ± 0.06 mg/g; p<0.05) and cross-sectional area (1626 ± 352 vs. 2234 ± 349 μm2; p<0.05), and increased connective tissue content (35 ± 7 vs. 10 ± 5%; p<0.05) compared to controls. Estrogen treatment decreased connective tissue density in the denervated and treated group (24 ± 4%; p<0.05) compared to the denervated group. It also prevented alterations on muscle glycogen in denervated and trated group. However, estrogen treatment did not prevent muscle atrophy (1626 ± 352 vs. 1712 ± 319 μm2). Conclusion: Estrogen treatment of rats' soleus muscles after denervation increased muscle glycogen content and minimized connective tissue density increase, but it did not prevent muscle atrophy.

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