Skeletal muscle disuse atrophy : implications on intracellular signaling pathways and mitochondrial permeability transition pore function

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

The Effect Of Pelvic Floor Muscle Training Alone Or In Combination With Electrostimulation In The Treatment Of Sexual Dysfunction In Women With Multiple Sclerosis.

Sexual dysfunction (SD) affects up to 80% of multiple sclerosis (MS) patients and pelvic floor muscles (PFMs) play an important role in the sexual function of these patients. The objective of this paper is to evaluate the impact of a rehabilitation program to treat lower urinary tract symptoms on SD of women with MS. Thirty MS women were randomly allocated to one of three groups: pelvic floor muscle training (PFMT) with electromyographic (EMG) biofeedback and sham neuromuscular electrostimulation (NMES) (Group I), PFMT with EMG biofeedback and intravaginal NMES (Group II), and PFMT with EMG biofeedback and transcutaneous tibial nerve stimulation (TTNS) (Group III). Assessments, before and after the treatment, included: PFM function, PFM tone, flexibility of the vaginal opening and ability to relax the PFMs, and the Female Sexual Function Index (FSFI) questionnaire. After treatment, all groups showed improvements in all domains of the PERFECT scheme. PFM tone and flexibility of the vaginal opening was lower after the intervention only for Group II. All groups improved in arousal, lubrication, satisfaction and total score domains of the FSFI questionnaire. This study indicates that PFMT alone or in combination with intravaginal NMES or TTNS contributes to the improvement of SD.

Effect Of Exercise Test On Pulmonary Function Of Obese Adolescents.

to investigate the pulmonary response to exercise of non-morbidly obese adolescents, considering the gender. a prospective cross-sectional study was conducted with 92 adolescents (47 obese and 45 eutrophic), divided in four groups according to obesity and gender. Anthropometric parameters, pulmonary function (spirometry and oxygen saturation [SatO2]), heart rate (HR), blood pressure (BP), respiratory rate (RR), and respiratory muscle strength were measured. Pulmonary function parameters were measured before, during, and after the exercise test. BP and HR were higher in obese individuals during the exercise test (p = 0.0001). SatO2 values decreased during exercise in obese adolescents (p = 0.0001). Obese males had higher levels of maximum inspiratory and expiratory pressures (p = 0.0002) when compared to obese and eutrophic females. Obese males showed lower values of maximum voluntary ventilation, forced vital capacity, and forced expiratory volume in the first second when compared to eutrophic males, before and after exercise (p = 0.0005). Obese females had greater inspiratory capacity compared to eutrophic females (p = 0.0001). Expiratory reserve volume was lower in obese subjects when compared to controls (p ≤ 0,05). obese adolescents presented changes in pulmonary function at rest and these changes remained present during exercise. The spirometric and cardiorespiratory values were different in the four study groups. The present data demonstrated that, in spite of differences in lung growth, the model of fat distribution alters pulmonary function differently in obese female and male adolescents.

Augmented β-cell Function And Mass In Glucocorticoid-treated Rodents Are Associated With Increased Islet Ir-β /akt/mtor And Decreased Ampk/acc And As160 Signaling.

Glucocorticoid (GC) therapies may adversely cause insulin resistance (IR) that lead to a compensatory hyperinsulinemia due to insulin hypersecretion. The increased β-cell function is associated with increased insulin signaling that has the protein kinase B (AKT) substrate with 160 kDa (AS160) as an important downstream AKT effector. In muscle, both insulin and AMP-activated protein kinase (AMPK) signaling phosphorylate and inactivate AS160, which favors the glucose transporter (GLUT)-4 translocation to plasma membrane. Whether AS160 phosphorylation is modulated in islets from GC-treated subjects is unknown. For this, two animal models, Swiss mice and Wistar rats, were treated with dexamethasone (DEX) (1 mg/kg body weight) for 5 consecutive days. DEX treatment induced IR, hyperinsulinemia, and dyslipidemia in both species, but glucose intolerance and hyperglycemia only in rats. DEX treatment caused increased insulin secretion in response to glucose and augmented β-cell mass in both species that were associated with increased islet content and increased phosphorylation of the AS160 protein. Protein AKT phosphorylation, but not AMPK phosphorylation, was found significantly enhanced in islets from DEX-treated animals. We conclude that the augmented β-cell function developed in response to the GC-induced IR involves inhibition of the islet AS160 protein activity.

Granulocyte Colony-stimulating Factor (g-csf) Positive Effects On Muscle Fiber Degeneration And Gait Recovery After Nerve Lesion In Mdx Mice.

G-CSF has been shown to decrease inflammatory processes and to act positively on the process of peripheral nerve regeneration during the course of muscular dystrophy. The aims of this study were to investigate the effects of treatment of G-CSF during sciatic nerve regeneration and histological analysis in the soleus muscle in MDX mice. Six-week-old male MDX mice underwent left sciatic nerve crush and were G-CSF treated at 7 days prior to and 21 days after crush. Ten and twenty-one days after surgery, the mice were euthanized, and the sciatic nerves were processed for immunohistochemistry (anti-p75(NTR) and anti-neurofilament) and transmission electron microscopy. The soleus muscles were dissected out and processed for H&E staining and subsequent morphologic analysis. Motor function analyses were performed at 7 days prior to and 21 days after sciatic crush using the CatWalk system and the sciatic nerve index. Both groups treated with G-CSF showed increased p75(NTR) and neurofilament expression after sciatic crush. G-CSF treatment decreased the number of degenerated and regenerated muscle fibers, thereby increasing the number of normal muscle fibers. The reduction in p75(NTR) and neurofilament indicates a decreased regenerative capacity in MDX mice following a lesion to a peripheral nerve. The reduction in motor function in the crushed group compared with the control groups may reflect the cycles of muscle degeneration/regeneration that occur postnatally. Thus, G-CSF treatment increases motor function in MDX mice. Nevertheless, the decrease in baseline motor function in these mice is not reversed completely by G-CSF.

Myoglobins: the link between discoloration and lipid oxidation in muscle and meat

Aerobic metabolism changes rapidly to glycolysis post-mortem resulting in a pH-decrease during the transformation of muscle in to meat affecting ligand binding and redox potential of the heme iron in myoglobin, the meat pigment. The inorganic chemistry of meat involves (i) redox-cycling between iron(II), iron(III), and iron(IV)/protein radicals; (ii) ligand exchange processes; and (iii) spin-equilibra with a change in coordination number for the heme iron. In addition to the function of myoglobin for oxygen storage, new physiological roles of myoglobin are currently being discovered, which notably find close parallels in the processes in fresh meat and nitrite-cured meat products. Myoglobin may be characterized as a bioreactor for small molecules like O2, NO, CO, CO2, H2O, and HNO with importance in bio-regulation and in protection against oxidative stress in vivo otherwise affecting lipids in membranes. Many of these processes may be recognised as colour changes in fresh meat and cured meat products under different atmospheric conditions, and could also be instructive for teaching purposes.

Effect of protein intake on bone and muscle mass in the elderly

The aging process is frequently characterized by an involuntary loss of muscle (sarcopenia) and bone (osteoporosis) mass. Both chronic diseases are associated with decreased metabolic rate, increased risk of falls fracture, and, as a result, increased morbidity and loss of independence in the elderly. The quality and quantity of protein intake affects bone and muscle mass in several ways and there is evidence that increased essential amino acid or protein availability can enhance muscle protein synthesis and anabolism, as well as improve bone homeostasis in older subjects. A thorough evaluation of renal function is important, since renal function decreases with age. Finally, protein and calcium intake should be considered in the prevention or treatment of the chronic diseases osteoporosis and sarcopenia

Chicken skeletal muscle-associated macroarray for gene discovery

Macro- and microarrays are well-established technologies to determine gene functions through repeated measurements of transcript abundance. We constructed a chicken skeletal muscle-associated array based on a muscle-specific EST database, which was used to generate a tissue expression dataset of similar to 4500 chicken genes across 5 adult tissues (skeletal muscle, heart, liver, brain, and skin). Only a small number of ESTs were sufficiently well characterized by BLAST searches to determine their probable cellular functions. Evidence of a particular tissue-characteristic expression can be considered an indication that the transcript is likely to be functionally significant. The skeletal muscle macroarray platform was first used to search for evidence of tissue-specific expression, focusing on the biological function of genes/transcripts, since gene expression profiles generated across tissues were found to be reliable and consistent. Hierarchical clustering analysis revealed consistent clustering among genes assigned to 'developmental growth', such as the ontology genes and germ layers. Accuracy of the expression data was supported by comparing information from known transcripts and tissue from which the transcript was derived with macroarray data. Hybridization assays resulted in consistent tissue expression profile, which will be useful to dissect tissue-regulatory networks and to predict functions of novel genes identified after extensive sequencing of the genomes of model organisms. Screening our skeletal-muscle platform using 5 chicken adult tissues allowed us identifying 43 'tissue-specific' transcripts, and 112 co-expressed uncharacterized transcripts with 62 putative motifs. This platform also represents an important tool for functional investigation of novel genes; to determine expression pattern according to developmental stages; to evaluate differences in muscular growth potential between chicken lines, and to identify tissue-specific genes.

The Function and Three-Dimensional Structure of a Thromboxane A(2)/Cysteinyl Leukotriene-Binding Protein from the Saliva of a Mosquito Vector of the Malaria Parasite

The highly expressed D7 protein family of mosquito saliva has previously been shown to act as an anti-inflammatory mediator by binding host biogenic amines and cysteinyl leukotrienes (CysLTs). In this study we demonstrate that AnSt-D7L1, a two-domain member of this group from Anopheles stephensi, retains the CysLT binding function seen in the homolog AeD7 from Aedes aegypti but has lost the ability to bind biogenic amines. Unlike any previously characterized members of the D7 family, AnSt-D7L1 has acquired the important function of binding thromboxane A(2) (TXA(2)) and its analogs with high affinity. When administered to tissue preparations, AnSt-D7L1 abrogated Leukotriene C(4) (LTC(4))-induced contraction of guinea pig ileum and contraction of rat aorta by the TXA(2) analog U46619. The protein also inhibited platelet aggregation induced by both collagen and U46619 when administered to stirred platelets. The crystal structure of AnSt-D7L1 contains two OBP-like domains and has a structure similar to AeD(7). In AnSt-D7L1, the binding pocket of the C-terminal domain has been rearranged relative to AeD7, making the protein unable to bind biogenic amines. Structures of the ligand complexes show that CysLTs and TXA(2) analogs both bind in the same hydrophobic pocket of the N-terminal domain. The TXA(2) analog U46619 is stabilized by hydrogen bonding interactions of the omega-5 hydroxyl group with the phenolic hydroxyl group of Tyr 52. LTC(4) and occupies a very similar position to LTE(4) in the previously determined structure of its complex with AeD7. As yet, it is not known what, if any, new function has been acquired by the rearranged C-terminal domain. This article presents, to our knowledge, the first structural characterization of a protein from mosquito saliva that inhibits collagen mediated platelet activation.

Exercise prevents the effects of experimental arthritis on the metabolism and function of immune cells

Active lymphocytes (LY) and macrophages (M Phi) are involved in the pathophysiology of rheumatoid arthritis (RA) Due to its anti-inflammatory effect. physical exercise may be beneficial in RA by acting on the immune system (IS) Thus, female Wistar rats with type II collagen-induced arthritis (CIA) were submitted to swimming training (6 weeks. 5 days/week. 60 min/day) and some biochemical and immune parameters, such as the metabolism of glucose and glutamine and function of LY and M. were evaluated In addition, plasma levels of some hormones and of interleukin-2 (IL-2) were also determined Results demonstrate that CIA increased lymphocyte proliferation (1.9- and 1 7-fold, respectively, in response to concanavalin A (ConA) and lipopolysaccharide (LPS)), as well as macrophage H(2)O(2) production (1 6-fold), in comparison to control Exercise training prevented the activation of immune cells, induced by CIA. and established a pattern of substrate utilization similar to that described as normal for these cells. Exercise also promoted an elevation of plasma levels of corticosterone (22 2%), progesterone (1 7-fold) and IL-2 (2 6-fold) Our data suggest that chronic exercise is able to counterbalance the effects of CIA on cells of the IS. reinforcing the proposal that the benefits of exercise may not be restricted to aerobic capacity and/or strength improvement Copyright (C) 2010 John Wiley & Sons, Ltd

Experimental chronic low-frequency resistance training produces skeletal muscle hypertrophy in the absence of muscle damage and metabolic stress markers

Volitional animal resistance training constitutes an important approach to modeling human resistance training. However, the lack of standardization protocol poses a frequent impediment to the production of skeletal muscle hypertrophy and the study of related physiological variables (i.e., cellular damage/inflammation or metabolic stress). Therefore, the purposes of the present study were: (1) to test whether a long-term and low frequency experimental resistance training program is capable of producing absolute increases in muscle mass; (2) to examine whether cellular damage/inflammation or metabolic stress is involved in the process of hypertrophy. In order to test this hypothesis, animals were assigned to a sedentary control (C, n = 8) or a resistance trained group (RT, n = 7). Trained rats performed 2 exercise sessions per week (16 repetitions per day) during 12 weeks. Our results demonstrated that the resistance training strategy employed was capable of producing absolute mass gain in both soleus and plantaris muscles (12%, p<0.05). Furthermore, muscle tumor necrosis factor (TNF-alpha) protein expression (soleus muscle) was reduced by 24% (p<0.01) in trained group when compared to sedentary one. Finally, serum creatine kinase (CK) activity and serum lactate concentrations were not affected in either group. Such information may have practical applications if reproduced in situations where skeletal muscle hypertrophy is desired but high mechanical stimuli of skeletal muscle and inflammation are not. Copyright (C) 2010 John Wiley & Sons, Ltd.

Exercise training changes IL-10/TNF-alpha ratio in the skeletal muscle of post-MI rats

Heart failure (HF) is associated with changes in the skeletal muscle (SM) which might be a consequence of the unbalanced local expression of pro- (TNF-alpha) and anti- (IL-10) inflammatory cytokines, leading to inflammation-induced myopathy, and SM wasting. This local effect of HF on SM may, on the other hand, contribute to systemic inflammation, as this tissue actively secretes cytokines. Since increasing evidence points out to an anti-inflammatory effect of exercise training, the goal of the present study was to investigate its effect in rats with HF after post-myocardial infarction (MI), with special regard to the expression of TNF-alpha and IL-10 in the soleus and extensor digitorum longus (EDL), muscles with different fiber composition. Wistar rats underwent left thoracotomy with ligation of the left coronary artery, and were randomly assigned to either a sedentary (Sham-operated and MI sedentary) or trained (Sham-operated and MI trained) group. Animals in the trained groups ran on a treadmill (0% grade at 13-20 m/min) for 60 min/day, 5 days/week, for 8-10 weeks. The training protocol was able to reverse the changes induced by MI, decreasing TNF-alpha protein (26%, P < 0.05) and mRNA (58%, P < 0.05) levels in the soleus, when compared with the sedentary MI group. Training also increased soleus IL-10 expression (2.6-fold, P < 0.001) in post-MI HF rats. As a consequence, the IL-10/TNF-alpha ratio was increased. This ""anti-inflammatory effect"" was more pronounced in the soleus than in the EDL, suggesting a fiber composition dependent response. (C) 2009 Elsevier Ltd. All rights reserved.

The effect of 5 days of aspartate and asparagine supplementation on glucose transport activity in rat muscle

The consumption of protein supplements containing amino acids is increasing around the world Aspartate (Asp) and asparagine (Asn) are amino acids metabolized by skeletal muscle. This metabolism involves biochemical pathways that are involved in increasing Krebs cycle activity via anaplerotic reactions. resulting in higher glutamine concentrations. A connection between amino acid supplementation, glycogen concentration, and glucose uptake has been previously demonstrated. The purpose of this study was to evaluate the effect of asp and Asn Supplementation on glucose uptake in rats using three different glycogen concentrations The results indicate that Asp and Asn supplementation in rats with high glycogen concentrations (fed state) further increased the glycogen concentration in the muscle, and decreased in vitro 2-deoxyglucose (a glucose analog.) uptake by the muscle at maximal insulin concentrations When animals had a medium glycogen concentration (consumed lard for 3 days). glucose uptake was higher in the supplemented group at sub-maximal insulin concentrations. We conclude that supplementation of Asp and Asn reduced glucose transport in rat muscle only at higher levels of glycogen. The ingestion of lard for 3 days changed the responsiveness and sensitivity to insulin, and that group had higher levels of insulin sensivity with Asp and Asn supplementation. Copyright (C) 2009 John Wiley & Sons, Ltd.

Adaptations in autonomic function during exercise training in heart failure

Although neurohumoral excitation is the hallmark of heart failure (HF), the mechanisms underlying this alteration are not entirely known. Abnormalities in several systems contribute to neurohumoral excitation in HF, including arterial and cardiopulmonary baroreceptors, central and peripheral chemoreceptors, cardiac chemoreceptors, and central nervous system abnormalities. Exercise intolerance is characteristic of chronic HF, and growing evidence strongly suggests that exercise limitation in patients with chronic HF is not due to elevated filling pressures or inadequate cardiac output during exercise, but instead due to skeletal myopathy. Several lines of evidence suggest that sympathetic excitation contributes to the skeletal myopathy of HF, since sympathetic activity mediates vasoconstriction at rest and during exercise likely restrains muscle blood flow, arteriolar dilatation, and capillary recruitment, leading to underperfused areas of working muscle, and areas of muscle ischemia, release of reactive oxygen species (ROS), and inflammation. Although controversial, either unmyelinated, metabolite-sensitive afferent fibers, and/or myelinated, mechanosensitive afferent fibers in skeletal muscle underlie the exaggerated sympathetic activity in HF. Exercise training has emerged as a unique non-pharmacological strategy for the treatment of HF. Regular exercise improves functional capacity and quality of life, and perhaps prognosis in chronic HF patients. Recent studies have provided convincing evidence that these benefits in chronic HF patients are mediated by significant reduction in central sympathetic outflow as a consequence of improvement in arterial and chemoreflex controls, and correction of central nervous system abnormalities, and increase in peripheral blood flow with reduction in cytokines and increase in mass muscle.

Exercise training improves muscle vasodilatation in individuals with T786C polymorphism of endothelial nitric oxide synthase gene

Negrão M.V, Alves CR, Alves G.B, Pereira A.C, Dias R.G, Laterza M.C, Mota G.F, Oliveira E.M, Bassaneze V, Krieger J.E, Negrão C.E, Rondon M.U.P. Exercise training improves muscle vasodilatation in individuals with T786C polymorphism of endothelial nitric oxide synthase gene. Physiol Genomics 42A: 71-77, 2010. First published July 6, 2010; doi:10.1152/physiolgenomics.00145.2009.-Allele T at promoter region of the eNOS gene has been associated with an increase in coronary disease mortality, suggesting that this allele increases susceptibility for endothelial dysfunction. In contrast, exercise training improves endothelial function. Thus, we hypothesized that: 1) Muscle vasodilatation during exercise is attenuated in individuals homozygous for allele T, and 2) Exercise training improves muscle vasodilatation in response to exercise for TT genotype individuals. From 133 preselected healthy individuals genotyped for the T786C polymorphism, 72 participated in the study: TT (n = 37; age 27 +/- 1 yr) and CT + CC (n = 35; age 26 +/- 1 yr). Forearm blood flow (venous occlusion plethysmography) and blood pressure (oscillometric automatic cuff) were evaluated at rest and during 30% handgrip exercise. Exercise training consisted of three sessions per week for 18 wk, with intensity between anaerobic threshold and respiratory compensation point. Resting forearm vascular conductance (FVC, P = 0.17) and mean blood pressure (P = 0.70) were similar between groups. However, FVC responses during handgrip exercise were significantly lower in TT individuals compared with CT + CC individuals (0.39 +/- 0.12 vs. 1.08 +/- 0.27 units, P = 0.01). Exercise training significantly increased peak VO(2) in both groups, but resting FVC remained unchanged. This intervention significantly increased FVC response to handgrip exercise in TT individuals (P = 0.03), but not in CT + CC individuals (P = 0.49), leading to an equivalent FVC response between TT and CT + CC individuals (1.05 +/- 0.18 vs. 1.59 +/- 0.27 units, P = 0.27). In conclusion, exercise training improves muscle vasodilatation in response to exercise in TT genotype individuals, demonstrating that genetic variants influence the effects of interventions such as exercise training.