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.

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 Automated fiber-type-specific cross-sectional area assessment and myonuclei counting in skeletal muscle

2013 ◽  
Vol 115 (11) ◽  
pp. 1714-1724 ◽  
Author(s):  
Fujun Liu ◽  
Christopher S. Fry ◽  
Jyothi Mula ◽  
Janna R. Jackson ◽  
Jonah D. Lee ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fiber ◽  
Fiber Type ◽  
Cross Sectional Area ◽  
Automated Image Analysis ◽  
Muscle Fiber Type ◽  
Sectional Area ◽  
Cross Sectional ◽  
Exercise Interventions ◽  
Structural And Functional Properties

Skeletal muscle is an exceptionally adaptive tissue that compromises 40% of mammalian body mass. Skeletal muscle functions in locomotion, but also plays important roles in thermogenesis and metabolic homeostasis. Thus characterizing the structural and functional properties of skeletal muscle is important in many facets of biomedical research, ranging from myopathies to rehabilitation sciences to exercise interventions aimed at improving quality of life in the face of chronic disease and aging. In this paper, we focus on automated quantification of three important morphological features of muscle: 1) muscle fiber-type composition; 2) muscle fiber-type-specific cross-sectional area, and 3) myonuclear content and location. We experimentally prove that the proposed automated image analysis approaches for fiber-type-specific assessments and automated myonuclei counting are fast, accurate, and reliable.

scholarly journals Skeletal muscle adaptations to microgravity exposure in the mouse

2003 ◽  
Vol 95 (6) ◽  
pp. 2462-2470 ◽  
Author(s):  
B. C. Harrison ◽  
D. L. Allen ◽  
B. Girten ◽  
L. S. Stodieck ◽  
P. J. Kostenuik ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fiber ◽  
Citrate Synthase ◽  
Space Shuttle ◽  
Immunohistochemical Analysis ◽  
Cross Sectional Area ◽  
Fiber Types ◽  
Sectional Area ◽  
Cross Sectional ◽  
Isoform Expression

To investigate the effects of microgravity on murine skeletal muscle fiber size, muscle contractile protein, and enzymatic activity, female C57BL/6J mice, aged 64 days, were divided into animal enclosure module (AEM) ground control and spaceflight (SF) treatment groups. SF animals were flown on the space shuttle Endeavour (STS-108/UF-1) and subjected to ∼11 days and 19 h of microgravity. Immunohistochemical analysis of muscle fiber cross-sectional area revealed that, in each of the muscles analyzed, mean muscle fiber cross-sectional area was significantly reduced ( P < 0.0001) for all fiber types for SF vs. AEM control. In the soleus, immunohistochemical analysis of myosin heavy chain (MHC) isoform expression revealed a significant increase in the percentage of muscle fibers expressing MHC IIx and MHC IIb ( P < 0.05). For the gastrocnemius and plantaris, no significant changes in MHC isoform expression were observed. For the muscles analyzed, no alterations in MHC I or MHC IIa protein expression were observed. Enzymatic analysis of the gastrocnemius revealed a significant decrease in citrate synthase activity in SF vs. AEM control.

scholarly journals An evaluation of the reliability of muscle fiber cross-sectional area and fiber number measurements in rat skeletal muscle

2013 ◽  
Vol 15 (1) ◽  
Author(s):  
Lisa Ceglia ◽  
Sathit Niramitmahapanya ◽  
Lori L Price ◽  
Susan S Harris ◽  
Roger A Fielding ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fiber ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Rat Skeletal Muscle ◽  
Cross Sectional ◽  
Fiber Number

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 Automated analysis of skeletal muscle fiber cross‐sectional area using CyteSeer image analysis program

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Tatiana Y Kostrominova ◽  
Randall Ingermanson ◽  
Casey A Laris ◽  
Patricia Loy ◽  
Patrick M McDonough
Keyword(s):  
Skeletal Muscle ◽  
Image Analysis ◽  
Muscle Fiber ◽  
Automated Analysis ◽  
Skeletal Muscle Fiber ◽  
Cross Sectional Area ◽  
Sectional Area ◽  
Analysis Program ◽  
Cross Sectional

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. 

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.

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