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.

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 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.

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.

scholarly journals Sequential alterations in the diameters of capillaries in rabbit skeletal muscle following deep transverse friction - a morphometric study

2005 ◽  
Vol 61 (2) ◽  
Author(s):  
M. A. Gregory ◽  
M. N. Deane ◽  
M. Marsh
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Muscle Blood Flow ◽  
Biceps Femoris ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Cross Sectional ◽  
Biceps Femoris Muscle ◽  
Beneficial Effects ◽  
The Cross

Objective: The precise mechanisms by which massage promotes repair in injured soft tissue are unknown. Various authorshave attributed the beneficial effects of massage to vasodilation and increased skin and muscle blood flow. The aim of this study was to determine whether deep transverse friction massage (DTF) causes capillary vasodilation in untraumatised skeletal muscle. Setting: Academic institution.Interventions: Twelve New Zealand white rabbits were anaesthetised and the left biceps femoris muscle received 10 minutes of DTF. Following treatment, wedge biopsies were taken from the musclewithin 10 minutes of treatment (R1 - 4), 24 hours (R5 - 8) and 6 days(R9 - 12) after treatment. To serve as controls, similar biopsies weretaken from the right biceps femoris of animals. The samples were fixed, dehydrated and embedded in epoxy resin.Transverse sections (1µm) of muscle were cut, stained with 1% aqueous alkaline toluidine blue and examined with a light microscope using a 40X objective. Images containing capillaries were captured using an image analyser with SIS software and the cross sectional diameters of at least 60 capillaries were measured from each specimen. Main Outcome Measures: Changes in capillary diameter. Results: The mean capillary diameters in control muscle averaged 4.76 µm. DTF caused a significant immediate increase of 17.3% in cross sectional area (p<0.001), which was not significantly increased by 10.0% after 24 hours (p>0.05). Six days after treatment the cross-sectional area of the treated muscle was 7.6% smaller than the controls. Conclusions: This confirms the contention that DTF stimulates muscle blood flow immediately after treatment and this may account for its beneficial effects in certain conditions. 

scholarly journals Exposure to cigarette smoke induces overexpression of von Hippel-Lindau tumor suppressor in mouse skeletal muscle

2012 ◽  
Vol 303 (6) ◽  
pp. L519-L527 ◽  
Author(s):  
Vladimir T. Basic ◽  
Elsa Tadele ◽  
Ali Ateia Elmabsout ◽  
Hongwei Yao ◽  
Irfan Rahman ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Tumor Suppressor ◽  
Cigarette Smoke ◽  
Muscle Fiber ◽  
Exercise Tolerance ◽  
Skeletal Muscles ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Cross Sectional ◽  
Von Hippel Lindau

Cigarette smoke (CS) is a well-established risk factor in the development of chronic obstructive pulmonary disease (COPD). In contrast, the extent to which CS exposure contributes to the development of the systemic manifestations of COPD, such as skeletal muscle dysfunction and wasting, remains largely unknown. Decreased skeletal muscle capillarization has been previously reported in early stages of COPD and might play an important role in the development of COPD-associated skeletal muscle abnormalities. To investigate the effects of chronic CS exposure on skeletal muscle capillarization and exercise tolerance, a mouse model of CS exposure was used. The 129/SvJ mice were exposed to CS for 6 mo, and the expression of putative elements of the hypoxia-angiogenic signaling cascade as well as muscle capillarization were studied. Additionally, functional tests assessing exercise tolerance/endurance were performed in mice. Compared with controls, skeletal muscles from CS-exposed mice exhibited significantly enhanced expression of von Hippel-Lindau tumor suppressor (VHL), ubiquitin-conjugating enzyme E2D1 (UBE2D1), and prolyl hydroxylase-2 (PHD2). In contrast, hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression was reduced. Furthermore, reduced muscle fiber cross-sectional area, decreased skeletal muscle capillarization, and reduced exercise tolerance were also observed in CS-exposed animals. Taken together, the current results provide evidence linking chronic CS exposure and induction of VHL expression in skeletal muscles leading toward impaired hypoxia-angiogenesis signal transduction, reduced muscle fiber cross-sectional area, and decreased exercise tolerance.

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.

Effects of 6 months of abiraterone acetate (AA) on muscle and adipose mass in men with metastatic castration-resistant prostate cancer (mCRPC).

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 222-222 ◽  
Author(s):  
Samuel Craig Brondfield ◽  
Vivian K. Weinberg ◽  
Kathryn M. Koepfgen ◽  
Arturo Molina ◽  
Charles J. Ryan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Muscle Wasting ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Cross Sectional ◽  
Adipose Mass

222 Background: AA, an inhibitor of androgen biosynthesis, has been shown to prolong overall survival in patients with mCRPC who have previously been treated with chemotherapy. Androgen deprivation therapy (ADT) has been shown to result in muscle wasting in prostate cancer pts. The effects of AA on progression of muscle and fat wasting have not been characterized. We evaluated whether 6 months of AA therapy altered total skeletal muscle mass or adipose mass. Methods: 10 sequential pts who responded to AA therapy for at least 6 months and had available computed tomography (CT) scans were retrospectively selected from the phase I-II COU-AA-002 study. CT image analysis was used to quantify change from baseline in total skeletal muscle and adipose tissue after 6 months of AA treatment. Skeletal muscle and adipose tissue cross-sectional area were calculated at the L3 level using Slice-O-Matic software V4.3. Previously published regression models were used to estimate fat-free mass, fat mass and skeletal muscle mass. Paired t-tests were performed to determine the change in measurements. Results: At baseline, 7 of 10 pts were overweight or obese (body mass index [BMI] > 25 kg/m2), and none were underweight. Advanced muscle wasting (sarcopenia, previously defined as the ratio of skeletal muscle cross-sectional area at L3 level to height < 52.4 cm2/m2) was present at baseline and 6 months in 9 of 10 pts. Over 6 months of AA treatment, pts lost an average of 1.9 kg ± 1.9 kg (p = 0.13). Mean changes (kg) (±standard deviation) in total skeletal muscle mass (−0.80 ± 1.71, p = 0.18) and total non-adipose mass (−1.44 ± 3.09, p = 0.17) were not significant. A significant decrease in total adipose mass (−0.61 ± 0.84, p = 0.048) was observed. Conclusions: Sarcopenia is prevalent in pts with mCRPC. AA was not related to significantly worsening sarcopenia or overall weight loss during the first 6 months of treatment; however, this may reflect a relatively short duration of therapy and/or small sample size. A significant loss of adipose tissue was observed, which is unexpected given the known effects of ADT, which increases adipose mass. Evaluation of additional AA treated patients is ongoing.

scholarly journals Role of TRPC1 channel in skeletal muscle function

2010 ◽  
Vol 298 (1) ◽  
pp. C149-C162 ◽  
Author(s):  
Nadège Zanou ◽  
Georges Shapovalov ◽  
Magali Louis ◽  
Nicolas Tajeddine ◽  
Chiara Gallo ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Function ◽  
Transient Receptor Potential ◽  
Force Production ◽  
Receptor Potential ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Skeletal Muscle Function ◽  
Cross Sectional

Skeletal muscle contraction is reputed not to depend on extracellular Ca2+. Indeed, stricto sensu , excitation-contraction coupling does not necessitate entry of Ca2+. However, we previously observed that, during sustained activity (repeated contractions), entry of Ca2+is needed to maintain force production. In the present study, we evaluated the possible involvement of the canonical transient receptor potential (TRPC)1 ion channel in this entry of Ca2+and investigated its possible role in muscle function. Patch-clamp experiments reveal the presence of a small-conductance channel (13 pS) that is completely lost in adult fibers from TRPC1−/−mice. The influx of Ca2+through TRPC1 channels represents a minor part of the entry of Ca2+into muscle fibers at rest, and the activity of the channel is not store dependent. The lack of TRPC1 does not affect intracellular Ca2+concentration ([Ca2+]i) transients reached during a single isometric contraction. However, the involvement of TRPC1-related Ca2+entry is clearly emphasized in muscle fatigue. Indeed, muscles from TRPC1−/−mice stimulated repeatedly progressively display lower [Ca2+]itransients than those observed in TRPC1+/+fibers, and they also present an accentuated progressive loss of force. Interestingly, muscles from TRPC1−/−mice display a smaller fiber cross-sectional area, generate less force per cross-sectional area, and contain less myofibrillar proteins than their controls. They do not present other signs of myopathy. In agreement with in vitro experiments, TRPC1−/−mice present an important decrease of endurance of physical activity. We conclude that TRPC1 ion channels modulate the entry of Ca2+during repeated contractions and help muscles to maintain their force during sustained repeated contractions.

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