scholarly journals Chronic disuse and skeletal muscle structure in older adults: sex-specific differences and relationships to contractile function

2015 ◽  
Vol 308 (11) ◽  
pp. C932-C943 ◽  
Author(s):  
Damien M. Callahan ◽  
Timothy W. Tourville ◽  
Mark S. Miller ◽  
Sarah B. Hackett ◽  
Himani Sharma ◽  
...  
Keyword(s):  
Older Adults ◽  
Skeletal Muscle ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Mitochondrial Content ◽  
Cross Sectional ◽  
Muscle Structure ◽  
Muscle Disuse

In older adults, we examined the effect of chronic muscle disuse on skeletal muscle structure at the tissue, cellular, organellar, and molecular levels and its relationship to muscle function. Volunteers with advanced-stage knee osteoarthritis (OA, n = 16) were recruited to reflect the effects of chronic lower extremity muscle disuse and compared with recreationally active controls ( n = 15) without knee OA but similar in age, sex, and health status. In the OA group, quadriceps muscle and single-fiber cross-sectional area were reduced, with the largest reduction in myosin heavy chain IIA fibers. Myosin heavy chain IIAX fibers were more prevalent in the OA group, and their atrophy was sex-specific: men showed a reduction in cross-sectional area, and women showed no differences. Myofibrillar ultrastructure, myonuclear content, and mitochondrial content and morphology generally did not differ between groups, with the exception of sex-specific adaptations in subsarcolemmal (SS) mitochondria, which were driven by lower values in OA women. SS mitochondrial content was also differently related to cellular and molecular functional parameters by sex: greater SS mitochondrial content was associated with improved contractility in women but reduced function in men. Collectively, these results demonstrate sex-specific structural phenotypes at the cellular and organellar levels with chronic disuse in older adults, with novel associations between energetic and contractile systems.

scholarly journals Effects of inhaled fluticasone propionate on extrinsic tongue muscles in rats

2020 ◽  
Vol 128 (3) ◽  
pp. 576-585
Author(s):  
Christopher Setzke ◽  
Oleg Broytman ◽  
John A. Russell ◽  
Natalie Morel ◽  
Michelle Sonsalla ◽  
...  
Keyword(s):  
Fluticasone Propionate ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Inhaled Corticosteroids ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Cross Sectional ◽  
Tetanic Force ◽  
Obstructive Sleep ◽  
Tongue Muscles

Obstructive sleep apnea (OSA) is more common in patients with asthma, and inhaled corticosteroids may contribute to OSA pathogenesis in these patients. This study tested the effects of orally inhaled fluticasone propionate (FP) on extrinsic tongue muscles. Unanesthetized rats were treated with FP or placebo for 28 days. On day 29, tongue retrusive and protrusive functions were tested via hypoglossal nerve stimulation under a state of anesthesia, followed by genioglossus (GG), styloglossus (SG) and hyoglossus (HG) muscle extraction, after euthanasia, for histology [myosin heavy chain (MHC) fibers and laminin content reflecting extracellular matrix (ECM)]. On protrusive testing, FP increased percent maximum tetanic force at 40 Hz ( P = 0.03 vs. placebo) and endurance index ( P = 0.029 vs. placebo). On retrusive testing, FP increased maximum twitch ( P = 0.026 vs. placebo) and tetanic forces ( P = 0.02 vs. placebo) with no effect on endurance index. On histology, FP increased GG cross-sectional area of MHC type IIa ( P = 0.036 vs. placebo) and tended to increase type IIb ( P = 0.057 vs. placebo) fibers and HG MHC IIx fibers ( P = 0.065). The FP group had significantly increased laminin-stained areas, of greatest magnitude in the HG muscle. FP affects tongue protrusive and retrusive functions differently, concurrent with a shift in MHC fibers and increased ECM accumulation. These differential alterations may destabilize the tongue’s “muscle hydrostat” during sleep and promote collapse. NEW & NOTEWORTHY The effects of inhaled corticosteroid on upper airway may contribute to OSA pathogenesis in asthma. In this study, we tested the effects of orally inhaled fluticasone propionate on tongue protrusive and retrusive functions and on tongue extrinsic muscle fiber composition and molecular properties. We found that fluticasone treatment: 1) increased protrusive endurance and retrusive maximum twitch and tetanic force; and 2) on histology, increased cross-sectional area of myosin heavy chain (MHC) type IIa fibers and tended to increase cross-sectional area of MHC type IIb fibers in the protrusive muscle and of MHC IIx fibers in the retrusors. It also increased laminin-stained areas, across extrinsic tongue muscles, of greatest magnitude in the retrusors; and 3) reduced protein degradation and activated pathways associated with increased protein synthesis in the protrusor. These differential effects on the protrusors and retrusors may destabilize the tongue’s “muscle hydrostat” properties during sleep and promote collapse.

Myonuclear number and myosin heavy chain expression in rat soleus single muscle fibers after spaceflight

1996 ◽  
Vol 81 (1) ◽  
pp. 145-151 ◽  
Author(s):  
D. L. Allen ◽  
W. Yasui ◽  
T. Tanaka ◽  
Y. Ohira ◽  
S. Nagaoka ◽  
...  
Keyword(s):  
Myosin Heavy Chain ◽  
Soleus Muscle ◽  
Heavy Chain ◽  
Muscle Fibers ◽  
Cross Sectional Area ◽  
Type I ◽  
Type Ii ◽  
Sectional Area ◽  
Cross Sectional ◽  
Fiber Size

The effects of 14 days of spaceflight on myonuclear number, fiber size, and myosin heavy chain (MHC) expression in isolated rat soleus muscle fiber segments were studied. Single soleus muscle fibers from rats flown on the Spacelab Life Sciences-2 14-day mission were compared with those from age-matched ground-based control rats by using confocal microscopy and gel electrophoresis. Spaceflight resulted in a significant reduction in the number of fibers expressing type I MHC and an increase in the number of fibers expressing type IIx or IIa MHC. Space-flight also resulted in an increase in the percentage of fibers coexpressing more than one MHC and in the reexpression of the neonatal isoform of MHC in some fibers. Fiber cross-sectional area was significantly reduced in pure type I MHC-expressing fibers and in fibers coexpressing type I+II MHC but not in fibers expressing one or more type II MHC in the flight rats. The number of myonuclei per millimeter was significantly reduced in type I MHC-expressing fibers from the flight rats but was not significantly different in type I+II and type II MHC-coexpressing fibers. Fibers expressing neonatal MHC were similar in size to control fibers but had significantly fewer myonuclei per millimeter than flight fibers not expressing neonatal MHC. In type I MHC-expressing fibers, the reduction in fiber cross-sectional area was greater than the reduction in myonuclear number; thus the average cytoplasmic volume per myonucleus was significantly lower in flight than in control fibers. The reduction in both myonuclear number and fiber size of fibers expressing type I MHC after 14 days of spaceflight supports the hypothesis that changes in the number of myonuclei may be a contributing factor to the reduction in fiber size associated with chronic unloading of the musculature.

scholarly journals Skeletal muscle atrophy and dysfunction in breast cancer patients: role for chemotherapy-derived oxidant stress

2018 ◽  
Vol 315 (5) ◽  
pp. C744-C756 ◽  
Author(s):  
Blas A. Guigni ◽  
Damien M. Callahan ◽  
Timothy W. Tourville ◽  
Mark S. Miller ◽  
Brad Fiske ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Skeletal Muscle ◽  
Cancer Patients ◽  
Muscle Fiber ◽  
Cross Sectional Area ◽  
Ros Production ◽  
Sectional Area ◽  
Breast Cancer Patients ◽  
Mitochondrial Content ◽  
Cross Sectional

How breast cancer and its treatments affect skeletal muscle is not well defined. To address this question, we assessed skeletal muscle structure and protein expression in 13 women who were diagnosed with breast cancer and receiving adjuvant chemotherapy following tumor resection and 12 nondiseased controls. Breast cancer patients showed reduced single-muscle fiber cross-sectional area and fractional content of subsarcolemmal and intermyofibrillar mitochondria. Drugs commonly used in breast cancer patients (doxorubicin and paclitaxel) caused reductions in myosin expression, mitochondrial loss, and increased reactive oxygen species (ROS) production in C2C12 murine myotube cell cultures, supporting a role for chemotherapeutics in the atrophic and mitochondrial phenotypes. Additionally, concurrent treatment of myotubes with the mitochondrial-targeted antioxidant MitoQ prevented chemotherapy-induced myosin depletion, mitochondrial loss, and ROS production. In patients, reduced mitochondrial content and size and increased expression and oxidation of peroxiredoxin 3, a mitochondrial peroxidase, were associated with reduced muscle fiber cross-sectional area. Our results suggest that chemotherapeutics may adversely affect skeletal muscle in patients and that these effects may be driven through effects of these drugs on mitochondrial content and/or ROS production.

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 Effects of long-term intradialytic oral nutrition and exercise on muscle protein homeostasis and markers of mitochondrial content in patients on hemodialysis

2020 ◽  
Vol 319 (5) ◽  
pp. F885-F894
Author(s):  
Jorge L. Gamboa ◽  
Serpil Muge Deger ◽  
Bradley W. Perkins ◽  
Cindy Mambungu ◽  
Feng Sha ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Resistance Exercise ◽  
Muscle Protein ◽  
Nutritional Supplementation ◽  
Sectional Area ◽  
Mitochondrial Content ◽  
Protein Energy Wasting ◽  
Cross Sectional ◽  
Protein Energy

Patients with end-stage kidney disease on maintenance hemodialysis commonly develop protein-energy wasting, a syndrome characterized by nutritional and metabolic abnormalities. Nutritional supplementation and exercise are recommended to prevent protein-energy wasting. In a 6-mo prospective randomized, open-label, clinical trial, we reported that the combination of resistance exercise and nutritional supplementation does not have an additive effect on lean body mass measured by dual-energy X-ray absorptiometry. To provide more mechanistic data, we performed a secondary analysis where we hypothesized that the combination of nutritional supplementation and resistance exercise would have additive effects on muscle protein accretion by stable isotope protein kinetic experiments, muscle mass by MRI, and mitochondrial content markers in muscle. We found that 6 mo of nutritional supplementation during hemodialysis increased muscle protein net balance [baseline: 2.5 (−17.8, 13.0) µg·100 mL−1·min−1 vs. 6 mo: 43.7 (13.0, 98.5) µg·100 mL−1·min−1, median (interquartile range), P = 0.04] and mid-thigh fat area [baseline: 162.3 (104.7, 226.6) cm2 vs. 6 mo: 181.9 (126.3, 279.2) cm2, median (interquartile range), P = 0.04]. Three months of nutritional supplementation also increased markers of mitochondrial content in muscle. Although the study is underpowered to detected differences, the combination of nutritional supplementation and exercise failed to show further benefit in protein accretion or muscle cross-sectional area. We conclude that long-term nutritional supplementation increases the skeletal muscle anabolic effect, the fat cross-sectional area of the thigh, and markers of mitochondrial content in skeletal muscle.

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.

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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