Página 1 dos resultados de 18913 itens digitais encontrados em 0.025 segundos

Aerobic exercise training upregulates skeletal muscle calpain and ubiquitin-proteasome systems in healthy mice

Cunha, Telma F.; Moreira, José B. N.; Paixão, Nathalie A.; Campos, Juliane C.; Monteiro, Alex W. A.; Bacurau, Aline V. N.; Bueno Junior, Carlos R.; Ferreira, Julio C. B.; Brum, Patricia C.
Fonte: AMER PHYSIOLOGICAL SOC; BETHESDA Publicador: AMER PHYSIOLOGICAL SOC; BETHESDA
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
66.41%
Cunha TF, Moreira JB, Paixao NA, Campos JC, Monteiro AW, Bacurau AV, Bueno CR Jr., Ferreira JC, Brum PC. Aerobic exercise training upregulates skeletal muscle calpain and ubiquitin-proteasome systems in healthy mice. J Appl Physiol 112: 1839-1846, 2012. First published March 29, 2012; doi:10.1152/japplphysiol.00346.2011.-Aerobic exercise training (AET) is an important mechanical stimulus that modulates skeletal muscle protein turnover, leading to structural rearrangement. Since the ubiquitin-proteasome system (UPS) and calpain system are major proteolytic pathways involved in protein turnover, we aimed to investigate the effects of intensity-controlled AET on the skeletal muscle UPS and calpain system and their association to training-induced structural adaptations. Long-lasting effects of AET were studied in C57BL/6J mice after 2 or 8 wk of AET. Plantaris cross-sectional area (CSA) and capillarization were assessed by myosin ATPase staining. mRNA and protein expression levels of main components of the UPS and calpain system were evaluated in plantaris by real-time PCR and Western immunoblotting, respectively. No proteolytic system activation was observed after 2 wk of AET. Eight weeks of AET resulted in improved running capacity, plantaris capillarization...

Avaliação da musculatura estriada de membros inferiores na limitação funcional ao exercício em pacientes com hipertensão arterial pulmonar; Assessment of skeletal muscle of lower limb in functional exercise limitation in patients with pulmonary arterial hypertension

Breda, Ana Paula
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 25/04/2011 PT
Relevância na Pesquisa
66.42%
Introdução: A hipertensão arterial pulmonar (HAP) é uma doença progressiva extremamente grave, que evolui com insuficiência cardíaca direita e morte. Apesar do avanço do tratamento farmacológico, o prognóstico permanece reservado com taxa de sobrevida de 86%, 70% e 55% em 1, 3 e 5 anos, respectivamente. A dispnéia progressiva e a intolerância ao exercício são as principais manifestações clínicas e refletem a falência do ventrículo direito. O músculo esquelético periférico parece ser também um dos principais determinantes desta limitação funcional, visto que a redução da oferta de oxigênio e alterações na extração/utilização do oxigênio pelo músculo são diretamente relacionados com a tolerância ao exercício. Existem dois mecanismos potencialmente envolvidos na regulação da oferta de oxigênio, e portanto, na capacidade de exercício: mecanismos centrais (função do coração, pulmão e sistema nervoso autônomo) e mecanismos periféricos (associado ao fluxo sanguíneo periférico e a função do músculo esquelético). Os pacientes com HAP geralmente apresentam baixo débito cardíaco e estado adrenérgico exacerbado. A combinação destas alterações pode resultar em alterações estruturais e funcionais da musculatura estriada periférica. Porém...

Efeitos do treinamento físico aeróbio em alta intensidade na musculatura esquelética de ratos infartados; Effects of high-intensity aerobic interval training on skeletal muscle of infarcted rats

Moreira, José Bianco Nascimento
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 14/02/2012 PT
Relevância na Pesquisa
66.46%
A miopatia esquelética em doenças sistêmicas é um importante preditor de mortalidade e prognóstico em diversas síndromes, incluindo a insuficiência cardíaca. Os danos músculo-esqueléticos em situações de comprometimento cardíaco são descritos pela literatura há décadas, entretanto, nenhum recurso farmacológico proposto até o momento mostrou-se eficiente em reverter esses prejuízos, ressaltando o papel do treinamento físico aeróbio. Apesar dos inegáveis benefícios desta terapia adjuvante no tratamento da insuficiência cardíaca, muito pouco se sabe sobre a intensidade de exercício capaz de otimizar os ganhos promovidos por esta intervenção. Dado isso, nesse estudo avaliamos a eficácia do treinamento físico aeróbio em alta intensidade na musculatura esquelética em ratos submetidos ao infarto do miocárdio, comparando-a com protocolo isocalórico realizado em intensidade moderada. Observamos que os animais infartados apresentaram alterações patológicas na musculatura esquelética, similarmente ao observado em pacientes com IC, como prejuízos em enzimas metabólicas fundamentais, atrofia muscular, perturbação da homeostase redox e ativação do complexo proteassomal 26S. Ambos os protocolos de treinamento físico aeróbio foram capazes de aprimorar substancialmente a capacidade funcional e potência aeróbia máxima nos animais infartados...

Papel dos receptores beta 2-adrenérgicos nas alterações musculoesqueléticas desencadeadas pela insuficiência cardíaca.; Role of beta2-adrenergic receptors on skeletal muscle alterations induced by heart failure

Voltarelli, Vanessa Azevedo
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 15/02/2012 PT
Relevância na Pesquisa
66.46%
A insuficiência cardíaca (IC) é uma síndrome complexa que envolve múltiplos sistemas e mecanismos compensatórios neuro-hormonais, acompanhada de altos índices de morbidade e mortalidade, e caracterizada por sintomas clínicos como fadiga, dispneia, e intolerância aos esforços físicos. Embora a IC seja uma síndrome de origem cardíaca, observam-se alterações em outros tecidos, como na musculatura esquelética. As modificações do fenótipo muscular e a perda de massa muscular esquelética observadas na IC contribuem para o mau prognóstico e para o aumento da mortalidade dos pacientes. Considerando que os receptores 2-adrenérgicos medeiam a atividade do sistema nervoso simpático na musculatura esquelética, e que a hiperatividade simpática é um dos principais componentes envolvidos no desenvolvimento da miopatia esquelética observada IC, sugere-se que estes receptores estejam associados às alterações morfofuncionais da musculatura esquelética na síndrome. Na presente Dissertação, avaliamos a contribuição dos receptores 2-adrenérgicos nas alterações metabólicas e morfofuncionais da musculatura esquelética e na intolerância aos esforços físicos decorrentes da IC. Para isso, utilizamos camundongos da linhagem FVB controles e com inativação gênica dos receptores 2-adrenérgicos (2KO) que foram submetidos à cirurgia de infarto ou à cirurgia fictícia (sham). O infarto induziu disfunção e remodelamento cardíacos nos animais controles...

Differential expression of myogenic regulatory factor MyoD in pacu skeletal muscle (Piaractus mesopotamicus Holmberg 1887: Serrasalminae, Characidae, Teleostei) during juvenile and adult growth phases

Alves de Almeida, Fernanda Losi; Carvalho, Robson Francisco; Pinhal, Danillo; Padovani, Carlos Roberto; Martins, Cesar; Dal Pai-Silva, Maeli
Fonte: Pergamon-Elsevier B.V. Ltd Publicador: Pergamon-Elsevier B.V. Ltd
Tipo: Artigo de Revista Científica Formato: 1306-1311
ENG
Relevância na Pesquisa
66.42%
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Processo FAPESP: 04/12756-3; Processo FAPESP: 05/56587-3; Skeletal muscle is the edible part of the fish. It grows by hypertrophy and hyperplasia, events regulated by differential expression of myogenic regulatory factors (MRFs). The study of muscle growth mechanisms in fish is very important in fish farming development. Pacu (Piaractus mesopotamicus) is one of the most important food species farmed in Brazil and has been extensively used in Brazilian aquaculture programs. The aim of this study was to analyze hyperplasia and hypertrophy and the MRF MyoD expression pattern in skeletal muscle of pacu (P. mesopotamicus) during juvenile and adult growth stages. Juvenile (n = 5) and adult (n = 5) fish were anaesthetized, sacrificed, and weight (g) and total length (cm) determined. White dorsal region muscle samples were collected and immersed in liquid nitrogen. Transverse sections (10 mu m thick) were stained with Haematoxilin-Eosin (HE) for morphological and morphometric analysis. Smallest fiber diameter from 100 muscle fibers per animal was calculated in each growth phase. These fibers were grouped into three classes (<20, 20-50, and >50 mu m) to evaluate hypertrophy and hyperplasia in white skeletal muscle. MyoD gene expression was determined by semi-quantitative RTPCR. PCR products were cloned and sequenced. juvenile and adult pacu skeletal muscle had similar morphology. The large number of <20 mu m diameter muscle fibers observed in juvenile fish confirms active hyperplasia. In adult fish...

Quantitative expression of myogenic regulatory factors MyoD and myogenin in pacu (Piaractus mesopotamicus) skeletal muscle during growth

Alves de Almeida, Fernanda Losi; Pessotti, Nabila Scabine; Pinhal, Danillo; Padovani, Carlos Roberto; Leitao, Natalia de Jesus; Carvalho, Robson Francisco; Martins, Cesar; Portella, Maria Celia; Dal Pai-Silva, Maeli
Fonte: Pergamon-Elsevier B.V. Ltd Publicador: Pergamon-Elsevier B.V. Ltd
Tipo: Outros Formato: 997-1004
ENG
Relevância na Pesquisa
66.41%
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); Processo FAPESP: 06/60446-9; Skeletal muscle growth is regulated by differential expression of myogenic regulatory factors (MRFs). We evaluated hyperplasia, hypertrophy and quantitative expression of MRFs MyoD and myogenin in 45, 90, 180, and 400 days post-hatching (dph) and adult pacu (Piaractus mesopotamicus) skeletal muscle. Transverse sections of white dorsal muscles were obtained to evaluate hypertrophy and hyperplasia. MyoD and myogenin gene expression was determined by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). Pacu skeletal muscle had similar morphology at all stages. The highest and the lowest frequencies of fiber diameters < 20 mu m were found at the 45 dph and adult stages, respectively. Their frequency was similar in the 90, 180, and 400 dph stages. The highest percentage of > 50 mu m diameter fibers were found in 180 and 400 dph, and adult fish. Hyperplasia was the main mechanism observed in pacu skeletal muscle growth at 45 dph; this declined through 90, 180, and 400 dph and remained low in adult fish; the latter presented hypertrophy as the main mechanism responsible for skeletal muscle growth. The high frequencies of 20-50 mu m diameter fibers at 90...

Heart failure alters MyoD and MRF4 expressions in rat skeletal muscle

Carvalho, Robson Francisco; Cicogna, Antonio Carlos; Campos, Gerson Eduardo Rocha; Lopes, Francis Da Silva; Sugizaki, Mário Mateus; Nogueira, Célia Regina; Pai-Silva, Maeli Dal
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica Formato: 219-225
ENG
Relevância na Pesquisa
66.43%
Heart failure (HF) is characterized by a skeletal muscle myopathy with increased expression of fast myosin heavy chains (MHCs). The skeletal muscle-specific molecular regulatory mechanisms controlling MHC expression during HF have not been described. Myogenic regulatory factors (MRFs), a family of transcriptional factors that control the expression of several skeletal muscle-specific genes, may be related to these alterations. This investigation was undertaken in order to examine potential relationships between MRF mRNA expression and MHC protein isoforms in Wistar rat skeletal muscle with monocrotaline-induced HF. We studied soleus (Sol) and extensor digitorum longus (EDL) muscles from both HF and control Wistar rats. MyoD, myogenin and MRF4 contents were determined using reverse transcription-polymerase chain reaction while MHC isoforms were separated using polyacrylamide gel electrophoresis. Despite no change in MHC composition of Wistar rat skeletal muscles with HF, the mRNA relative expression of MyoD in Sol and EDL muscles and that of MRF4 in Sol muscle were significantly reduced, whereas myogenin was not changed in both muscles. This down-regulation in the mRNA relative expression of MRF4 in Sol was associated with atrophy in response to HF while these alterations were not present in EDL muscle. Taken together...

Ca2+–calmodulin-dependent protein kinase expression and signalling in skeletal muscle during exercise

Rose, Adam J; Kiens, Bente; Richter, Erik A
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
66.42%
Ca2+ signalling is proposed to play an important role in skeletal muscle function during exercise. Here, we examined the expression of multifunctional Ca2+–calmodulin-dependent protein kinases (CaMK) in human skeletal muscle and show that CaMKII and CaMKK, but not CaMKI or CaMKIV, are expressed. Furthermore, the effect of exercise duration and intensity on skeletal muscle CaMKII activity and phosphorylation of downstream targets was examined. Eight healthy men exercised at ∼67% of peak pulmonary O2 uptake (V̇o2peak) with muscle samples taken at rest and after 1, 10, 30, 60 and 90 min of exercise. Ten other men exercised for three consecutive 10 min bouts at 35%, 60% and 85% V̇o2peak with muscle samples taken at rest, at the end of each interval and 30 min post-exercise. There was a rapid and transient increase in autonomous CaMKII activity and CaMKII phosphorylation at Thr287 in skeletal muscle during exercise. Furthermore, the phosphorylation of phospholamban (PLN) at Thr17, which was identified as a CaMKII substrate in skeletal muscle, was rapidly (< 1 min) increased by exercise, and remained phosphorylated 5-fold above basal level during 90 min of exercise. The phosphorylation of serum response factor at Ser103, a putative CaMKII substrate...

Slow- and fast-twitch rat hind limb skeletal muscle phenotypes 8 months after spinal cord transection and olfactory ensheathing glia transplantation

Negredo, Pilar; Rivero, José-Luis L; González, Beatriz; Ramón-Cueto, Almudena; Manso, Rafael
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
66.42%
Paralysed skeletal muscle of rats with spinal cord injury (SCI) undergoes atrophy and a switch in gene expression pattern which leads to faster, more fatigable phenotypes. Olfactory ensheathing glia (OEG) transplants have been reported to promote axonal regeneration and to restore sensory-motor function in animals with SCI. We hypothesized that OEG transplants could attenuate skeletal muscle phenotypic deterioration and that this effect could underlie the functional recovery observed in behavioural tests. A variety of morphological, metabolic and molecular markers were assessed in soleus (SOL) and extensor digitorum longus (EDL) muscles of spinal cord transected (SCT), OEG-transplanted rats 8 months after the intervention and compared with non-transplanted SCT rats and sham-operated (without SCT) controls (C). A multivariate analysis encompassing all the parameters indicated that OEG-transplanted rats displayed skeletal muscle phenotypes intermediate between non-transplanted and sham-operated controls, but different from both. A high correlation was observed between behaviourally tested sensory-motor functional capacity and expression level of slow- and fast-twitch hind limb skeletal muscle phenotypic markers, particularly the histochemical glycerol-3-phosphate dehydrogenase activity (−0.843...

Exercise induces expression of leukaemia inhibitory factor in human skeletal muscle

Broholm, Christa; Mortensen, Ole Hartvig; Nielsen, Søren; Akerstrom, Thorbjorn; Zankari, Alaa; Dahl, Benny; Pedersen, Bente Klarlund
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
66.43%
The leukaemia inhibitory factor (LIF) belongs to the interleukin (IL)-6 cytokine superfamily and is constitutively expressed in skeletal muscle. We tested the hypothesis that LIF expression in human skeletal muscle is regulated by exercise. Fifteen healthy young male volunteers performed either 3 h of cycle ergometer exercise at ∼60% of (n = 8) or rested (n = 7). Muscle biopsies were obtained from the vastus lateralis prior to exercise, immediately after exercise, and at 1.5, 3, 6 and 24 h post exercise. Control subjects had biopsy samples taken at the same time points as during the exercise trial. Skeletal muscle LIF mRNA increased immediately after the exercise and declined gradually during recovery. However, LIF protein was unchanged at the investigated time points. Moreover, we tested the hypothesis that LIF mRNA and protein expressions are modulated by calcium (Ca2+) in primary human skeletal myocytes. Treatment of myocytes with the Ca2+ ionophore, ionomycin, for 6 h resulted in an increase in both LIF mRNA and LIF protein levels. This finding suggests that Ca2+ may be involved in the regulation of LIF in endurance-exercised skeletal muscle. In conclusion, primary human skeletal myocytes have the capability to produce LIF in response to ionomycin stimulation and LIF mRNA levels increase in skeletal muscle following concentric exercise. The finding that the increase in LIF mRNA levels is not followed by a similar increase in skeletal muscle LIF protein suggests that other exercise stimuli or repetitive stimuli are necessary in order to induce a detectable accumulation of LIF protein.

Calprotectin is released from human skeletal muscle tissue during exercise

Mortensen, Ole Hartvig; Andersen, Kasper; Fischer, Christian; Nielsen, Anders Rinnov; Nielsen, Søren; Åkerström, Thorbjörn; Aastrøm, Maj-brit; Borup, Rehannah; Pedersen, Bente Klarlund
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
66.45%
Skeletal muscle has been identified as a secretory organ. We hypothesized that IL-6, a cytokine secreted from skeletal muscle during exercise, could induce production of other secreted factors in skeletal muscle. IL-6 was infused for 3 h into healthy young males (n = 7) and muscle biopsies obtained at time points 0, 3 and 6 h in these individuals and in resting controls. Affymetrix microarray analysis of gene expression changes in skeletal muscle biopsies identified a small set of genes changed by IL-6 infusion. RT-PCR validation confirmed that S100A8 and S100A9 mRNA were up-regulated 3-fold in skeletal muscle following IL-6 infusion compared to controls. Furthermore, S100A8 and S100A9 mRNA levels were up-regulated 5-fold in human skeletal muscle following cycle ergometer exercise for 3 h at ∼60% of in young healthy males (n = 8). S100A8 and S100A9 form calprotectin, which is known as an acute phase reactant. Plasma calprotectin increased 5-fold following acute cycle ergometer exercise in humans, but not following IL-6 infusion. To identify the source of calprotectin, healthy males (n = 7) performed two-legged dynamic knee extensor exercise for 3 h with a work load of ∼50% of peak power output and arterial–femoral venous differences were obtained. Arterial plasma concentrations for calprotectin increased 2-fold compared to rest and there was a net release of calprotectin from the working muscle. In conclusion...

AMP-activated protein kinase regulates nicotinamide phosphoribosyl transferase expression in skeletal muscle

Brandauer, Josef; Vienberg, Sara G; Andersen, Marianne A; Ringholm, Stine; Risis, Steve; Larsen, Per S; Kristensen, Jonas M; Frøsig, Christian; Leick, Lotte; Fentz, Joachim; Jørgensen, Sebastian; Kiens, Bente; Wojtaszewski, Jørgen F P; Richter, Erik A;
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
66.42%
Deacetylases such as sirtuins (SIRTs) convert NAD to nicotinamide (NAM). Nicotinamide phosphoribosyl transferase (Nampt) is the rate-limiting enzyme in the NAD salvage pathway responsible for converting NAM to NAD to maintain cellular redox state. Activation of AMP-activated protein kinase (AMPK) increases SIRT activity by elevating NAD levels. As NAM directly inhibits SIRTs, increased Nampt activation or expression could be a metabolic stress response. Evidence suggests that AMPK regulates Nampt mRNA content, but whether repeated AMPK activation is necessary for increasing Nampt protein levels is unknown. To this end, we assessed whether exercise training- or 5-amino-1-β-d-ribofuranosyl-imidazole-4-carboxamide (AICAR)-mediated increases in skeletal muscle Nampt abundance are AMPK dependent. One-legged knee-extensor exercise training in humans increased Nampt protein by 16% (P < 0.05) in the trained, but not the untrained leg. Moreover, increases in Nampt mRNA following acute exercise or AICAR treatment (P < 0.05 for both) were maintained in mouse skeletal muscle lacking a functional AMPK α2 subunit. Nampt protein was reduced in skeletal muscle of sedentary AMPK α2 kinase dead (KD), but 6.5 weeks of endurance exercise training increased skeletal muscle Nampt protein to a similar extent in both wild-type (WT) (24%) and AMPK α2 KD (18%) mice. In contrast...

Contractility and kinetics of human fetal and human adult skeletal muscle

Racca, Alice W; Beck, Anita E; Rao, Vijay S; Flint, Galina V; Lundy, Scott D; Born, Donald E; Bamshad, Michael J; Regnier, Michael
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
66.46%
Little is known about the contraction and relaxation properties of fetal skeletal muscle, and measurements thus far have been made with non-human mammalian muscle. Data on human fetal skeletal muscle contraction are lacking, and there are no published reports on the kinetics of either fetal or adult human skeletal muscle myofibrils. Understanding the contractile properties of human fetal muscle would be valuable in understanding muscle development and a variety of muscle diseases that are associated with mutations in fetal muscle sarcomere proteins. Therefore, we characterised the contractile properties of developing human fetal skeletal muscle and compared them to adult human skeletal muscle and rabbit psoas muscle. Electron micrographs showed human fetal muscle sarcomeres are not fully formed but myofibril formation is visible. Isolated myofibril mechanical measurements revealed much lower specific force, and slower rates of isometric force development, slow phase relaxation, and fast phase relaxation in human fetal when compared to human adult skeletal muscle. The duration of slow phase relaxation was also significantly longer compared to both adult groups, but was similarly affected by elevated ADP. F-actin sliding on human fetal skeletal myosin coated surfaces in in vitro motility (IVM) assays was much slower compared with adult rabbit skeletal myosin...

The role of skeletal muscle PLIN proteins at rest and following lipolytic stimulation

MacPherson, Rebecca EK
Fonte: Brock University Publicador: Brock University
Tipo: Electronic Thesis or Dissertation
ENG
Relevância na Pesquisa
66.43%
This thesis investigated the subcellular location of skeletal muscle PLIN proteins (PLIN2, PLIN3, and PLIN5) as well as protein interactions with ATGL and HSL at rest and following lipolytic stimulation. In addition, the serine phosphorylation state of PLIN2, PLIN3, and PLIN5 was determined at rest and following lipolytic stimulation. An isolated whole muscle technique was used to study the effects of contraction and epinephrine-induced lipolysis. This method allowed for the examination of the effects of contraction and epinephrine alone and in combination. Further, the soleus was chosen for investigating the role of PLIN proteins in skeletal muscle lipolysis due to its suitability for isolated incubation, and the fact that it is primarily oxidative in nature (~80% type I fibres). It has also been previously shown to have the greatest reliance on lipid metabolism and for this reason is ideal for investigating the role of PLIN proteins in lipolysis. Immunofluorescence microscopy revealed that skeletal muscle lipid droplets are partially co-localized to both PLIN2 and PLIN5 and that contraction does not affect the amount of colocalization, indicating that PLIN5 is not recruited to lipid droplets with contraction (PLIN2 ~65%; PLIN5 ~56%). Results from the immunoprecipitation studies revealed that with lipolysis in skeletal muscle the interaction between ATGL and CGI-58 is increased (study 2: 128% with contraction...

Toll-like receptor 4 modulates skeletal muscle substrate metabolism

Frisard, M.; McMillan, R.; Marchand, J.; Wahlberg, K.; Wu, Y.; Voelker, K.; Heilbronn, L.; Haynie, K.; Muoio, B.; Li, L.; Hulver, M.
Fonte: Amer Physiological Soc Publicador: Amer Physiological Soc
Tipo: Artigo de Revista Científica
Publicado em //2010 EN
Relevância na Pesquisa
66.45%
Toll-like receptor 4 (TLR4), a protein integral to innate immunity, is elevated in skeletal muscle of obese and type 2 diabetic humans and has been implicated in the development of lipid-induced insulin resistance. The purpose of this study was to examine the role of TLR4 as a modulator of basal (non-insulin-stimulated) substrate metabolism in skeletal muscle with the hypothesis that its activation would result in reduced fatty acid oxidation and increased partitioning of fatty acids toward neutral lipid storage. Human skeletal muscle, rodent skeletal muscle, and skeletal muscle cell cultures were employed to study the functional consequences of TLR4 activation on glucose and fatty acid metabolism. Herein, we demonstrate that activation of TLR4 with low (metabolic endotoxemia) and high (septic conditions) doses of LPS results in increased glucose utilization and reduced fatty acid oxidation in skeletal muscle and that these changes in metabolism in vivo occur in concert with increased circulating triglycerides. Moreover, animals with a loss of TLR4 function possess increased oxidative capacity in skeletal muscle and present with lower fasting levels of triglycerides and nonesterified free fatty acids. Evidence is also presented to suggest that these changes in substrate metabolism under metabolic endotoxemic conditions are independent of skeletal muscle-derived proinflammatory cytokine production. This report illustrates that skeletal muscle is a target for circulating endotoxin and may provide critical insight into the link between a proinflammatory state and dysregulated metabolism as observed with obesity...

Endocannabinoids and skeletal muscle glucose uptake.

Cavuoto, Paul
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Tese de Doutorado
Publicado em //2010
Relevância na Pesquisa
66.44%
Obesity is a risk factor for type 2 diabetes mellitus and cardiovascular disease. Obesity, in particular when the fat is predominantly visceral, is associated with insulin resistance and a reduced ability to increase the rate of fat oxidation in response to an increase in dietary fat intake. Skeletal muscle is a primary site for insulin-stimulated glucose uptake. Insulin responsiveness in skeletal muscle is regulated by a number of factors including growth hormone, cortisol, sex steroids, cytokines secreted by inflammatory cells and adipocytes, fatty acids, and fatty acid derivatives such as the endocannabinoids. The most abundant endocannabinoids, anandamide (AEA) and 2- arachidonoylglycerol (2-AG) are synthesised from arachidonic acid. They have autocrine or paracrine mechanisms of action which are rapidly terminated by cellular uptake and subsequent metabolism by fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) which degrades AEA and 2-AG, respectively. AEA and 2-AG are ligands for the cannabinoid receptor type 1 (CB₁) and the cannabinoid receptor type 2 (CB₂ ); both are 7 transmembrane domain G-protein coupled receptors. AEA and 2-AG also bind to the transient receptor potential channel-vanilloid sub-family member 1 (TRPV1). TRPV1 is a putative sixtransmembrane domain protein with a pore region between segments five and six and cytoplasmic N and C termini. TRPV1 was initially discovered as a receptor for capsaicin...

Transgenic Overexpression of miR-133a in Skeletal Muscle

Deng, Zhongliang; Chen, Jian-Fu; Wang, Da-Zhi
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
EN_US
Relevância na Pesquisa
66.46%
Background: MicroRNAs (miRNAs) are a class of non-coding regulatory RNAs of ~22 nucleotides in length. miRNAs regulate gene expression post-transcriptionally, primarily by associating with the 3' untranslated region (UTR) of their regulatory target mRNAs. Recent work has begun to reveal roles for miRNAs in a wide range of biological processes, including cell proliferation, differentiation and apoptosis. Many miRNAs are expressed in cardiac and skeletal muscle, and dysregulated miRNA expression has been correlated with muscle-related disorders. We have previously reported that the expression of muscle-specific miR-1 and miR-133 is induced during skeletal muscle differentiation and miR-1 and miR-133 play central regulatory roles in myoblast proliferation and differentiation in vitro. Methods: In this study, we measured the expression of miRNAs in the skeletal muscle of mdx mice, an animal model for human muscular dystrophy. We also generated transgenic mice to overexpress miR-133a in skeletal muscle. Results: We examined the expression of miRNAs in the skeletal muscle of mdx mice. We found that the expression of muscle miRNAs, including miR-1a, miR-133a and miR-206, was up-regulated in the skeletal muscle of mdx mice. In order to further investigate the function of miR-133a in skeletal muscle in vivo...

Slow- and fast-twitch rat hind limb skeletal muscle phenotypes 8 months after spinal cord transection and olfactory ensheathing glia transplantation

Negredo, Pilar; Rivero, José-Luis L.; González, Beatriz; Ramón-Cueto, Almudena; Manso, Rafael
Fonte: Physiological Society (Great Britain) Publicador: Physiological Society (Great Britain)
Tipo: Artículo Formato: 3785634 bytes; application/pdf
ENG
Relevância na Pesquisa
66.43%
18 pages, 6 figures, 1 table.-- PMID: 18372308 [PubMed]; Paralyzed skeletal muscle of rats with spinal cord injury (SCI) undergoes atrophy and a switch in gene expression pattern which leads to faster, more fatigable phenotypes. Olfactory ensheathing glia (OEG) transplants have been reported to promote axonal regeneration and to restore sensory-motor function in animals with SCI. We hypothesized that OEG-transplants could attenuate skeletal muscle phenotypic deterioration and that this effect could underlie the functional recovery observed in behavioural tests. A variety of morphologic, metabolic and molecular markers were assessed in soleus (SOL) and extensor digitorum longus (EDL) muscles of spinal cord transected (SCT), OEG-transplanted rats eight months after the intervention and compared with non-transplanted SCT-rats and sham-operated (without SCT) controls (C). A multivariate analysis encompassing all the parameters indicated that OEGtransplanted rats displayed skeletal muscle phenotypes intermediate between nontransplanted and sham-operated controls, but different from both. A high correlation was observed between behaviourally-tested sensory-motor functional capacity and expression level of slow- and fast-twitch hind limb skeletal muscle phenotypic markers...

Role of Thioredoxin-Interacting Protein (TXNIP) in Regulating Redox Balance and Mitochondrial Function in Skeletal Muscle

DeBalsi, Karen Lynn
Fonte: Universidade Duke Publicador: Universidade Duke
Tipo: Dissertação
Publicado em //2013
Relevância na Pesquisa
66.43%

The Muoio lab studies the interplay between lipid whole body energy balance,

mitochondrial function and insulin action in skeletal muscle. Data from our lab suggests that lipid-induced insulin resistance in skeletal muscle may stem from excessive incomplete oxidation of fatty acids, which occurs when high rates of β-­oxidation exceed TCA cycle flux (Koves et al., 2005; Koves et al., 2008). Most notably, we have shown that mice with a genetically engineered decrease in mitochondrial uptake and oxidation of fatty acids are protected against diet-­induced insulin resistance (Koves et al., 2008). This

suggests that an excessive and/or inappropriate metabolic burden on muscle

mitochondria provokes insulin resistance. Our working model predicts that: 1) high rates of incomplete β-oxidation reflect a state of ”mitochondrial stress,” and 2) that energy-overloaded mitochondria generate a yet unidentified signal that mediates insulin

resistance. One possibility is that this putative mitochondrial-derived signal stems from redox imbalance and disruptions in redox sensitive signaling cascades. Therefore, we are interested in identifying molecules that link redox balance, mitochondrial function and insulin action in skeletal muscle. The work described herein identifies thioredoxin-interacting protein (TXNIP) as an attractive candidate that regulates both glucose homeostasis and mitochondrial fuel selection.

TXNIP is a redox sensitive...

Role of MicroRNAs in Human Skeletal Muscle Tissue Engineering In Vitro

Cheng, Cindy Sue
Fonte: Universidade Duke Publicador: Universidade Duke
Tipo: Dissertação
Publicado em //2014
Relevância na Pesquisa
66.46%

The development of a functional tissue-engineered human skeletal muscle model in vitro would provide an excellent platform on which to study the process of myogenesis, various musculoskeletal disease states, and drugs and therapies for muscle toxicity. We developed a protocol to culture human skeletal muscle bundles in a fibrin hydrogel under static conditions capable of exerting active contractions. Additionally, we demonstrated the use of joint miR-133a and miR-696 inhibition for acceleration of muscle differentiation, elevation of active contractile force amplitudes, and increasing Type II myofiber formation in vitro.

The global hypothesis that motivated this research was that joint inhibition of miR-133a and miR-696 in isolated primary human skeletal myoblasts would lead to accelerated differentiation of tissue-engineered muscle constructs with higher proportion of Type I myofibers and that are capable of significantly increased active contractile forces when subjected to electrical stimulus. The proposed research tested the following specific hypotheses: (1) that HSkM would require different culture conditions than those optimal for C2C12 culture (8% equine serum in differentiation medium on uncoated substrates), as measured by miR expression...