Navegando por Palavras-chave "Skeletal muscle"

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    Aerobic exercise training rescues protein quality control disruption on white skeletal muscle induced by chronic kidney disease in rats
    (Wiley, 2018) Moraes, Wilson Max Almeida Monteiro de [UNIFESP]; Souza, Pamella Ramona Moraes de; Paixao, Nathalie Alves de; Sousa, Luis Gustavo Oliveira de; Ribeiro, Daniel Araki [UNIFESP]; Marshall, Andrea G.; Prestes, Jonato; Irigoyen, Maria Claudia; Brum, Patricia Chakur; Medeiros, Alessandra [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    We tested whether aerobic exercise training (AET) would modulate the skeletal muscle protein quality control (PQC) in a model of chronic kidney disease (CKD) in rats. Adult Wistar rats were evaluated in four groups: control (CS) or trained (CE), and 5/6 nephrectomy sedentary (5/6NxS) or trained (5/6NxE). Exercised rats were submitted to treadmill exercise (60 min., five times/wk for 2 months). We evaluated motor performance (tolerance to exercise on the treadmill and rotarod), cross-sectional area (CSA), gene and protein levels related to the unfolded protein response (UPR), protein synthesis/survive and apoptosis signalling, accumulated misfolded proteins, chymotrypsin-like proteasome activity (UPS activity), redox balance and heat-shock protein (HSP) levels in the tibialis anterior. 5/6NxS presented a trend towards to atrophy, with a reduction in motor performance, down-regulation of protein synthesis and up-regulation of apoptosis signalling; increases in UPS activity, misfolded proteins, GRP78, derlin, HSP27 and HSP70 protein levels, ATF4 and GRP78 genes; and increase in oxidative damage compared to CS group. In 5/6NxE, we observed a restoration in exercise tolerance, accumulated misfolded proteins, UPS activity, protein synthesis/apoptosis signalling, derlin, HSPs protein levels as well as increase in ATF4, GRP78 genes and ATF6α protein levels accompanied by a decrease in oxidative damage and increased catalase and glutathione peroxidase activities. The results suggest a disruption of PQC in white muscle fibres of CKD rats previous to the atrophy. AET can rescue this disruption for the UPR, prevent accumulated misfolded proteins and reduce oxidative damage, HSPs protein levels and exercise tolerance.
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    Análises morfofuncionais, bioquímicas e moleculares de modelo experimental de miopatia associada à estatina
    (Universidade Federal de São Paulo (UNIFESP), 2017-03-06) Andrade, Pamela Vieira de [UNIFESP]; Silva, Helga Cristina Almeida da [UNIFESP]; Silva, Ismael Dale Cotrim Guerreiro da [UNIFESP]; http://lattes.cnpq.br/7917312029683516; http://lattes.cnpq.br/0844918862241102; http://lattes.cnpq.br/3536599065009604; Universidade Federal de São Paulo (UNIFESP)
    Introdução: As estatinas atualmente são consideradas os agentes mais úteis para o tratamento da hipercolesterolemia. Nos últimos anos, aumentaram os relatos sobre efeitos colaterais importantes no músculo esquelético, com mialgia, aumento dos valores séricos de creatinoquinase (CK) e até rabdomiólise após uso de altas doses dessas medicações. O reconhecimento precoce da miopatia induzida pelas estatinas e a descontinuação das estatinas é fundamental na prevenção da miopatia e diminuição de possíveis sequelas. Objetivos: 1. Estudar o efeito da estatina sobre a contração e contratura muscular em ratos expostos a baixas e altas concentrações da sinvastatina 2. Correlacionar essas alterações com a morfologia, bioquímica e proteômica da fibra muscular e 3. Analisar o uso do bloqueador de canal de liberação de cálcio (dantrolene) no presente modelo. Material e Métodos: O estudo foi realizado com 50 ratos machos Wistar, divididos em 5 grupos: A - Controle; B - Estatina baixa dose (5 mg/kg/dia); C - Estatina alta dose (20 mg/kg/dia); D – Sem estatina, com dantrolene (5 mg/Kg); E – Estatina alta dose (20 mg/kg/dia) e dantrolene (5 mg/Kg). Os animais dos grupos B, C e E receberam a sinvastatina diariamente, diluída com carboximetilcelulose (CMC) 0,5%, via gavagem, por dois meses; os do grupo A e D receberam apenas o veículo (CMC), via gavagem, por dois meses; os dos grupos D e E receberam ainda dantrolene (5 mg/Kg) via subcutânea por dois meses. Os animais foram pesados semanalmente, sendo anotado o consumo da dieta líquida e sólida diariamente; a cada sete dias foram realizados exames físico e neurológico. Após dois meses, os animais foram anestesiados para a retirada dos músculos vastos laterais, gastrocnêmios e sóleos. Com os vastos laterais foram realizados testes de estimulação elétrica in vitro em presença de halotano e cafeína - nos quais as curvas de contração e contratura de cada teste foram analisadas - e teste de estimulação tetânica pré e pós-isquemia - referido como grau de contração após cada estímulo elétrico. Com os gastrocnêmios e os sóleos foi realizado estudo morfológico (histologia e morfometria). O gastrocnêmio foi empregado ainda para estudo bioquímico, feito pela quantificação do malonaldeído (MDA), e análise proteômica por espectrometria de massas. Resultados: Na estimulação elétrica in vitro na presença de cafeína, houve aumento significativo nos valores de contração nas concentrações de 1; 1,5; 2; 3, 4 e 32 mM de cafeína do grupo C em relação aos outros grupos. Não houve diferença significativa da contração em resposta a diferentes concentrações de halotano e a diferentes estimulações tetânicas pré e pós-isquemia, bem como não houve diferença no grau de contratura após vários estímulos. Houve aumento significativo na produção de MDA no grupo C em relação ao grupo B. O estudo morfológico qualitativo mostrou, na reação do Tricrômico de Gomori, pequenos aglomerados fucsinofílicos grosseiros na periferia das fibras musculares, vistos mais uniformemente no grupo C. Na análise morfométrica do músculo gastrocnêmio, pela coloração de hematoxilina/eosina, houve diminuição significante da área transversa das fibras musculares no grupo C em relação aos grupos D e E. Na análise proteômica houve aumento significativo da expressão das proteínas glicolíticas nos grupos tratados com estatina. Conclusão: Nossos dados mostraram que, apesar dos animais não apresentarem miopatia clínica evidente, doses de estatina de 20 mg/Kg/dia aumentaram a contração muscular após estímulo com cafeína, provocaram alterações morfológicas mitocondriais com atrofia do músculo gastrocnêmio e aumentaram a peroxidação lipídica no músculo.
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    Avaliação da capacidade funcional em idosos ativos: estudo transversal
    (Universidade Federal de São Paulo (UNIFESP), 2018-08-10) Santos, Carlos André Freitas dos [UNIFESP]; Loturco Filho, Irineu [UNIFESP]; http://lattes.cnpq.br/0370724009248558; http://lattes.cnpq.br/6601225200882781; Universidade Federal de São Paulo (UNIFESP)
    BACKGROUND: The process of muscle aging is initially characterized by progressive loss of muscle power. Subsequently, there is loss of strength and muscle mass. Hence, geriatric syndromes, such as sarcopenia and frailty, have a high prevalence. Therefore, it is necessary to study which physical tests are best correlated with lower limb muscle performance. OBJECTIVES: To study the association of the functional capacity of the elderly, through functional tests used in clinical practice, with classic tests and gold standard of body composition and muscular function. MATERIAL AND METHOD: Cross-sectional study with elderly people who practiced regular physical exercises. The functional tests evaluated were: the sit to stand 5 times test, gait speed, SPPB, hand grip, the 30-s chair-stand test and TUGT. The classic and gold standard evaluations were: vertical jump test with squatting (SJ), vertical jump test with counter-movement (CMJ), isokinetic tests (peak torque in the concentric contraction at 60o.s-1 in extensor muscles and knee flexors), measurement of the appendicular skeletal muscle mass and percentage of body fat by DEXA. The statistical evaluations were: Pearson correlation coefficient (R), Student t test and split analysis of the medians. RESULTS: Fifty-four elderly participated in the study with 71 (± 6.5) years old: 41 (76%) women and 13 (24%) men. The ratio of hand grip performance and concentric isokinetic tests at velocity 60o.s-1 had r = 0.72 and r = 0.69 for knee extensors and flexors, respectively (p <0.05). The relation of hand grip performance and vertical jump tests was r = 0.55 and r = 0.53, for SJ and CMJ, respectively (p <0.05). The relationship between hand grip performance and appendicular skeletal muscle index was r = 0.49 (p <0.05). The relationship between the SA performance and isokinetic evaluation 60o.s-1 was r = 0.50 and r = 0.47 for the knee extensor and flexor muscles, respectively (p <0.05). The relationship between CMJ performance and Isokinetic evaluation 60o.s-1 was r = 0.55 and r = 0.50 for the knee extensor and flexor muscles, respectively (p <0.05). Elderly who jumped 15cm or more (SCM), had the best performances in 5 of the 6 functional tests (p <0.05). Elderly with body fat percentage greater or equal 38.6%, were worse in the sit up chair test (p <0.05). CONCLUSION: In this way, the palmar grip strength test is an initial indicator of changes in important components in the aging process, such as lean mass, strength, and muscle power. Among the tests that specifically involve the lower limbs, SCM in contact platform, can be used in clinical practice in the evaluation of strength and muscular power of the elderly.
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    Calcium influx through L-type channels attenuates skeletal muscle contraction via inhibition of adenylyl cyclases
    (Elsevier B.V., 2013-11-15) Menezes-Rodrigues, Francisco Sandro [UNIFESP]; Pires-Oliveira, Marcelo [UNIFESP]; Duarte, Thiago [UNIFESP]; Paredes-Gamero, Edgar Julian [UNIFESP]; Chiavegatti, Tiago [UNIFESP]; Godinho, Rosely Oliveira [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Skeletal muscle contraction is triggered by acetylcholine induced release of Ca2+ from sarcoplasmic reticulum. Although this signaling pathway is independent of extracellular Ca2+, L-type voltage gated calcium channel (Ca-v) blockers have inotropic effects on frog skeletal muscles which occur by an unknown mechanism. Taking into account that skeletal muscle fiber expresses Ca+2-sensitive adenylyl cyclase (AC) isoforms and that cAMP is able to increase skeletal muscle contraction force, we investigated the role of Ca2+ influx on mouse skeletal muscle contraction and the putative crosstalk between extracellular Ca2+ and intracellular LAMP signaling pathways. the effects of Ca-v blockers (verapamil and nifedipine) and extracellular Ca2+ chelator EGTA were evaluated on isometric contractility of mouse diaphragm muscle under direct electrical stimulus (supramaximal voltage, 2 ms, 0.1 Hz). Production of LAMP was evaluated by radiometric assay while Ca2+ transients were assessed by confocal microscopy using L6 cells loaded with fluo-4/AM. Ca2+ channel blockers verapamil and nifedipine had positive inotropic effect, which was mimicked by removal of extracellular Ca+2 with EGTA or Ca2+-free Tyrode. While phosphodiesterase inhibitor IBMX potentiates verapamil positive inotropic effect, it was abolished by AC inhibitors SQ22536 and NYK80. Finally, the inotropic effect of verapamil was associated with increased intracellular cAMP content and mobilization of intracellular Ca2+, indicating that positive inotropic effects of Ca2+ blockers depend on cAMP formation. Together, our results show that extracellular Ca2+ modulates skeletal muscle contraction, through inhibition of Ca2+-sensitive AC. the cross-talk between extracellular calcium and cAMP-dependent signaling pathways appears to regulate the extent of skeletal muscle contraction responses. (C) 2013 Elsevier B.V. All rights reserved.
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    Caracterização farmacológica do efeito da crotamina sobre o músculo esquelético de camundongo empregando ensaios ex vivo e in vivo
    (Universidade Federal de São Paulo (UNIFESP), 2017) Lima, Sunamita de Carvalho [UNIFESP]; Hayashi, Mirian Akemi Furuie [UNIFESP]; Godinho, Rosely Oliveira [UNIFESP]; http://lattes.cnpq.br/4929571824508354; http://lattes.cnpq.br/5559309395232147; http://lattes.cnpq.br/0255664511512988; Universidade Federal de São Paulo (UNIFESP)
    Apesar dos vários estudos científicos conduzidos até o momento, visando entender e explorar as diferentes funções e atividades biológicas da crotamina, pouco se sabe ainda sobre o mecanismo de ação envolvido no seu efeito sobre o tecido muscular. Embora a ação da crotamina sobre a musculatura esquelética tenha sido a principal motivação para a sua descoberta e para a realização dos primeiros experimentos farmacológicos com o intuito de identificar os principais alvos e mecanismo de ação deste polipeptídeo, apenas o envolvimento dos canais de Na+ foi sugerido até o momento, mas que também foi descartado como alvo por outros pesquisadores empregando técnicas eletrofisiológicas, que permitiram demonstrar que este peptídeo não atua diretamente sobre as subunidades alfa dos canais de Na+ humanos expressos em células renais HEK293. Por outro lado, considerando que a crotamina bloqueia os canais de K+ voltagem-dependente encontrados em células excitáveis, propomos realizar concomitantemente estudos ex vivo e in vivo com o intuito de avaliar a possível importância da ação da crotamina sobre estes canais iônicos para promoção da síndrome da paralisia das patas traseiras em camundongos. Verificamos pela primeira vez uma resposta dose-dependente para a paralisia induzida pela crotamina, no qual a imobilização foi observada mais rapidamente para as maiores doses utilizadas. E ainda, ativadores e/ou bloqueadores de canais de Na+ ou K+ afetam tanto o efeito inotrópico positivo em musculatura esquelética isolada, como no tempo decorrido para a observação da síndrome da paralisia dos membros traseiros de camundongos promovidos pela administração da crotamina. Embora não tenha sido possível identificar os fatores determinantes para a imobilização seletiva dos membros posteriores dos camundongos, a comprovação do envolvimento dos canais de Na+ e K+ no aumento de força de contração promovido pela crotamina permitem sugerir possíveis novas aplicações para esta molécula, como o seu uso em disfunções musculares características, como as presentes na caquexia e fadiga muscular, observados em pacientes com câncer e sob tratamento com quimioterápicos.
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    Chronic low frequency/low volume resistance training reduces pro-inflammatory cytokine protein levels and TLR4 mRNA in rat skeletal muscle
    (Springer, 2010-08-01) Zanchi, Nelo Eidy; Lira, Fabio Santos [UNIFESP]; Siqueira Filho, Mario Alves de; Rosa, Jose Cesar [UNIFESP]; Oliveira Carvalho, Carla Roberta de; Seelaender, Marilia; Santos, Ronaldo Vagner Thomatieli dos [UNIFESP]; Lancha, Antonio Herbert; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)
    Skeletal muscle is the source of pro- and anti-inflammatory cytokines, and recently, it has been recognized as an important source of interleukin 6 (IL-6), a cytokine that exerts inhibitory effects on several pro-inflammatory cytokines. Although dynamic chronic resistance training has been shown to produce the known repeated bout effect, which abolishes the acute muscle damage, performing of high-intensity resistance training has been regarded highly advisable, at least from the hypertrophy perspective. On the other hand, a more therapeutic, non-damaging resistance training program, mainly composed of concentric forces, low frequency/low volume of training, and the same exercise, could theoretically benefit the muscle when the main issue is to avoid muscle inflammation (as in the treatment of several low-grade inflammatory diseases) because the acute effect of each resistance exercise session could be diminished/avoided, at the same time that the muscle is still being overloaded in a concentric manner. However, the benefits of such less demanding resistance training schedule on the muscle inflammatory profile have never been investigated. Therefore, we assessed the protein expression of IL-6, TNF-alpha, IL-10, IL-10/TNF-alpha ratio, and HSP70 levels and mRNA expression of SCF(beta-TrCP), IL-15, and TLR-4 in the skeletal muscle of rats submitted to resistance training. Briefly, animals were randomly assigned to either a control group (S, n = 8) or a resistance-trained group (T, n = 7). Trained rats were exercised over a duration of 12 weeks (two times per day, two times per week). Detection of IL-6, TNF-alpha, IL-10, and HSP70 protein expression was carried out by western blotting and SCF(beta-TrCP) (SKP Cullin F-Box Protein Ligases), a class of enzymes involved in the ubiquitination of protein substrates to proteasomal degradation, IL-15, and TLR-4 by RT-PCR. Our results show a decreased expression of TNF-alpha and TLR4 mRNA (40 and 60%, respectively; p < 0.05) in the plantar muscle from trained, when compared with control rats. in conclusion, exercise training induced decreased TNF-alpha and TLR-4 expressions, resulting in a modified IL-10/TNF-alpha ratio in the skeletal muscle. These data show that, in healthy rats, 12-week resistance training, predominantly composed of concentric stimuli and low frequency/low volume schedule, down regulates skeletal muscle production of cytokines involved in the onset, maintenance, and regulation of inXammation.
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    Chronic resistance training decreases MuRF-1 and Atrogin-1 gene expression but does not modify Akt, GSK-3 beta and p70S6K levels in rats
    (Springer, 2009-06-01) Zanchi, Nelo Eidy; Siqueira Filho, Mario Alves de; Lira, Fabio Santos [UNIFESP]; Rosa, Jose Cesar [UNIFESP]; Yamashita, Alex Shimura; Oliveira Carvalho, Carla Roberta de; Seelaender, Marilia; Lancha, Antonio Herbert; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)
    Long-term adaptation to resistance training is probably due to the cumulative molecular effects of each exercise session. Therefore, we studied in female Wistar rats the molecular effects of a chronic resistance training regimen (3 months) leading to skeletal muscle hypertrophy in the plantaris muscle. Our results demonstrated that muscle proteolytic genes MuRF-1 and Atrogin-1 were significantly decreased in the exercised group measured 24 h after the last resistance exercise session (41.64 and 61.19%, respectively; P < 0.05). Nonetheless, when measured at the same time point, 4EBP-1, GSK-3 beta and eIF2B epsilon mRNA levels and Akt, GSK-3 beta and p70S6K protein levels (regulators of translation initiation) were not modified. Such data suggests that if gene transcription constitutes a control point in the protein synthesis pathway this regulation probably occurs in early adaptation periods or during extreme situations leading to skeletal muscle remodeling. However, proteolytic gene expression is modified even after a prolonged resistance training regimen leading to moderate skeletal muscle hypertrophy.
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    Consequências das lesões térmicas extensas no músculo esquelético de crianças: uma revisão sistemática da literatura.
    (Universidade Federal de São Paulo, 2021-02-22) Horta, Célia Cristina [UNIFESP]; De Oliveira, Flavia [UNIFESP]; http://lattes.cnpq.br/3387760393535776; http://lattes.cnpq.br/7223874543088348; Universidade Federal de São Paulo (UNIFESP)
    As lesões térmicas que ocorrem por derramamento de líquidos quentes estão entre os acidentes mais comuns. Quando superiores a 40% da extensão corporal são consideradas extensas e, além de respostas locais, levam a repercussões sistêmicas. Dentre tais repercussões estão o hipermetabolismo, o catabolismo proteico, e como consequência ocorre a perda de massa muscular e o atraso no crescimento, dentre outras sequelas. Desta forma, o objetivo deste trabalho é fazer uma revisão sistemática da literatura de pesquisas que envolvam seres humanos e animais sobre as consequências das lesões térmicas extensas no músculo esquelético, como comprometimento sistêmico, em crianças. Além disso, discutir a importância desses dados para a reabilitação fisioterapêutica de pacientes queimados. Para isso, foram selecionados e avaliados artigos em inglês indexados nas bases de dados PubMed (National Library of Medicine and National Institutes of Health). Foram utilizadas como palavras-chave, no idioma já mencionado: “burn injury” or “thermal injury” and children and “skeletal muscle”. Foram selecionados 34 artigos originais, sendo 21 estudos com experimentação animal e 13 estudos clínicos com seres humanos. Com isso, este trabalho conclui que a reabilitação de crianças queimadas através da fisioterapia imediata em hospitais promove sua melhora funcional e sistemática, além de aumentar a qualidade de vida através de programas de exercícios que promovam fortalecimento muscular e ganho de massa magra.
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    Cyclooxygenase-2 expression in skeletal muscle of knockout mice suffering Duchenne muscular dystrophy
    (Springer, 2013-05-01) Flavia, De Oliveira [UNIFESP]; Quintana, Hananiah Tardivo [UNIFESP]; Bortolin, Jeferson Andre [UNIFESP]; Gomes, Odair Alfredo; Liberti, Edson Aparecido; Ribeiro, Daniel Araki [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Univ Ribeirao Preto; Universidade de São Paulo (USP)
    The purpose of the present study was to investigate the role of cyclooxygenase-2 (COX-2) expression in fibrotic lesion in mdx mice. A total of six male C57BL/10 mice and six C57BL/10-DMD/mdx were distributed into two groups: control and animals with Duchenne muscular dystrophy (DMD). the medial part of gastrocnemius muscle was evaluated being the specimens stained with hematoxylin and eosin (H&E) and Sirius Red under normal and polarized light to differentiate type I (red and yellow) and III (green) collagen. COX-2 expression was assessed by immunohistochemistry. the results revealed histopathological changes in C57BL/10-DMD/mdx as depicted by regenerating fibers. Sirius Red stain showed a substantial increase in the amount of type I collagen of mdx mice. DMD induced a strong COX-2 immunoexpression in intercellular space. Taken together, our results are consistent with the notion that necrotic and fibrotic lesions are able to increase COX-2 expression in DMD.
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    Dipeptidyl peptidase IV inhibition upregulates GLUT4 translocation and expression in heart and skeletal muscle of spontaneously hypertensive rats
    (Elsevier B.V., 2013-01-05) Giannocco, Gisele [UNIFESP]; Oliveira, Kelen Carneiro [UNIFESP]; Crajoinas, Renato O.; Venturini, Gabriela; Salles, Thiago A.; Fonseca-Alaniz, Miriam H.; Maciel, Rui Monteiro de Barros [UNIFESP]; Girardi, Adriana C. C.; Fac Med ABC; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)
    The purpose of the current study was to test the hypothesis that the dipeptidyl peptidase IV (DPPIV) inhibitor sitagliptin, which exerts anti-hyperglycemic and anti-hypertensive effects, upregulates GLUT4 translocation, protein levels, and/or mRNA expression in heart and skeletal muscle of spontaneously hypertensive rats (SHRs). Ten days of treatment with sitagliptin (40 mg/kg twice daily) decreased plasma DPPIV activity in both young (Y, 5-week-old) and adult (A, 20-week-old) SHRs to similar extents ( similar to 85%). However, DPPIV inhibition only lowered blood pressure in Y-SHRs (119 +/- 3 vs. 136 +/- 4 mmHg). GLUT4 translocation, total protein levels and mRNA expression were decreased in the heart, soleus and gastrocnemius muscle of SHRs compared to age-matched Wistar Kyoto (WKY) normotensive rats. These differences were much more pronounced between A-SHRs and A-WKY rats than between Y-SHRs and Y-WKY rats. in Y-SHRs, sitagliptin normalized GLUT4 expression in the heart, soleus and gastrocnemius. in A-SHRs, sitagliptin increased GLUT4 expression to levels that were even higher than those of A-WKY rats. Sitagliptin enhanced the circulating levels of the DPPIV substrate glucagon-like peptide-1 (GLP-1) in SHRs. in addition, stimulation of the GLP-1 receptor in cardiomyocytes isolated from SHRs increased the protein level of GLUT4 by 154 +/- 13%. Collectively, these results indicate that DPPIV inhibition upregulates GLUT4 in heart and skeletal muscle of SHRs. the underlying mechanism of sitagliptin-induced upregulation of GLUT4 in SHRs may be, at least partially, attributed to GLP-1. (C) 2012 Elsevier B.V. All rights reserved.
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    Downhill exercise-induced changes in gene expression related with macrophage polarization and myogenic cells in the triceps long head of rats
    (Springer, 2015-02-01) Minari, André Luis Araújo [UNIFESP]; Oyama, Lila Missae [UNIFESP]; Santos, Ronaldo Vagner Thomatieli dos [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Macrophages are one of the most heterogenic immune cells involved in skeletal muscle regeneration. After skeletal muscle damage, M1 phenotypes exhibit pro-inflammatory reaction. in a later stage, they are converted to M2 phenotypes with anti-inflammatory properties. To study when gene expressions of macrophage polarization are changed after damage induced by downhill exercise to exhaustion is the objective of this paper. Before (CTRL) and 0 h (G0), 24 h (G24), 48 h (G48) and 72 h (G72) after 18 bouts of downhill exercise, the animals were euthanised, and the triceps were dissected. We measured gene expression of macrophages (CD68 and CD163), myogenic cells (MyoD and myogenin) and quantified cytokine secretion (interleukin (IL)-6, IL-10 and tumour necrosis factor alpha (TNF-alpha)). the CD68 expression was lower in G72 compared with G24 (P = 0.005) while CD163 was higher in G48 compared with G24 (P = 0.04). the MyoD expression was higher in G72 compared with G0 (P = 0.04). the myogenin expression was lower in G24 compared with CTRL (P = 0.01) and restored in G72 compared with G24 (P = 0.007). the TNF-alpha was significantly higher at all times after 24 h (all compared with CTRL, with P = 0.03). the CD68 and CD163 expressions behaved distinctly after exercise, which indicates macrophage polarization between 24 and 48 h. the distinct expression of myogenin, concomitantly with MyoD elevation in G72, indicates that myogenic cell differentiation and the significant change of TNF-alpha level show an important role of this cytokine in these processes.
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    Doxorubicin caused severe hyperglycaemia and insulin resistance, mediated by inhibition in AMPk signalling in skeletal muscle
    (Wiley-Blackwell, 2016) de Lima Junior, Edson Alves; Yamashita, Alex Shimura; Pimentel, Gustavo Duarte; De Sousa, Luis G. O.; Santos, Ronaldo Vagner Thomatieli dos [UNIFESP]; Goncalves, Cinara Ludvig; Streck, Emilio Luiz; de Lira, Fabio Santos; Rosa Neto, Jose Cesar
    Background Cancer is considered the second leading cause of death in the world, and for the treatment of this disease, pharmacological intervention strategies are frequently based on chemotherapy. Doxorubicin (DOX) is one of the most widely used chemotherapeutic agents in clinical practice for treating a number of solid tumours. The treatment with DOX mimics some effects of cancer cachexia, such as anorexia, asthenia, decreases in fat and skeletal muscle mass and fatigue. We observed that treatment with DOX increased the systemic insulin resistance and caused a massive increase in glucose levels in serum. Skeletal muscle is a major tissue responsible for glucose uptake, and the positive role of AMPk protein (AMP-activated protein kinase) in GLUT-4 (Glucose Transporter type 4) translocation, is well established. With this, our aim was to assess the insulin sensitivity after treatment with DOX and involvement of AMPk signalling in skeletal muscle in this process. Methods We used Wistar rats which received a single dose of doxorubicin (DOX group) or saline (CT group) intraperitoneally at a dose of 15mg/kg b.w. The expression of proteins involved in insulin sensitivity, glucose uptake, inflammation, and activity of electron transport chain was assessed in extensor digitorum longus muscle, as well as the histological evaluation. In vitro assays were performed in L6 myocytes to assess glucose uptake after treatment with DOX. Agonist of AMPk [5-aminoimidazole-4-carboxamide (AICAR)] and the antioxidant n-acetyl cysteine were used in L6 cells to evaluate its effect on glucose uptake and cell viability. Results The animals showed a significant insulin resistance, hyperglycaemia, and hyperinsulinemia. A decrease in the expression of AMKP and GLUT-4 was observed in the extensor digitorum longus muscle. Also in L6 cells, DOX leads to a decrease in glucose uptake, which is reversed with AICAR. Conclusions DOX leads to conditions similar to cachexia, with severe glucose intolerance both in vivo and in vitro. The decrease of AMPk activity of the protein is modulated negatively with DOX, and treatment with agonist of AMPk (AICAR) has proved to be a possible therapeutic target, which is able to recover glucose sensitivity in skeletal muscle.
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    Efeito do exercício exaustivo sobre aspectos inflamatórios no músculo esquelético e tecido adiposo de ratos
    (Universidade Federal de São Paulo (UNIFESP), 2010-04-28) Rosa Neto, José Cesar [UNIFESP]; Nascimento, Claudia Maria da Penha Oller do [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Aim: to verify the inflammatory effects of exhaustive exercise on adipose tissue (mesenteric and retroperitoneal), and skeletal muscle (sóleus: fiber type I, EDL: Fyber type II). Methods: Wistar rats were randomly assigned to four groups: group control and group exercised until exhaustion, these rats were sacrificed in three different times, after the exhaustion, two hours after and six hours after exhaustive exercise. Cytokines IL-2, IL-4, TNF-α, IL-6 and IL-10 were analyzed by mRNA (PCR Real Time) and protein (ELISA) expression. TLR-4 and your inflammatory via (TRAF6, MYD88), were analyzed by Western Blotting. Results: IL-6, IL-10 and TNF-α were elevated in all tissues and groups compared with control group. However, IL-10/TNF-α ratio was higher in skeletal muscle, and opposite response was found in adipose tissue. TLR-4 and your via was elevated in adipose tissue, but not altered in skeletal muscle after exhaustive exercise. The concentrations of IL-2 and IL-4 were altered in skeletal muscle, but were not modulated in adipose tissue, after exercise protocol. Conclusion: exhaustive exercise showed one increased in anti-inflammatory response in skeletal muscle, by increased of IL-10/TNF-α ratio. On the other hand, adipose tissue showed increased in inflammatory response, evidenced by decreased in IL-10/TNF-α ratio and increased in TLR-4 content. Moreover, the IL-4 was increased in EDL, concomitant with raised in Myod. This results could showed one increased in hyperplasia in skeletal muscle.
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    Efeito do treinamento físico aeróbio sobre a apoptose da musculatura esquelética de ratos espontaneamente hipertensos
    (Universidade Federal de São Paulo (UNIFESP), 2013-02-18) Matsuo Junior, Eduardo Hiroshi [UNIFESP]; Medeiros, Alessandra [UNIFESP]; Ribeiro, Daniel Araki [UNIFESP]; http://lattes.cnpq.br/9969803499258672; http://lattes.cnpq.br/0071198026371230; http://lattes.cnpq.br/0088252656781637; Universidade Federal de São Paulo (UNIFESP)
    A hipertensão arterial é uma doença que está associada com alterações na musculatura esquelética, podendo existir fenótipos pró-apoptóticos que podem levar às disfunções deste órgão, trazendo sérios riscos e prejuízos à saúde, como fadiga excessiva e menor força e contratilidade. Sobre a apoptose, este evento é responsável pela morte celular programada, ou seja, ele regula o desaparecimento das células de forma ordenada e bem definida, sendo um evento essencial para a vida do ser humano. Porém, na hipertensão arterial, o evento apoptótico ocorre de maneira desordenada, ou seja, em excesso e causando prejuízos. Dessa forma, o presente estudo analisou o efeito do treinamento físico aeróbio sobre a apoptose na musculatura esquelética de ratos espontaneamente hipertensos (SHR). Neste estudo utilizamos 12 ratos SHR e 12 ratos Wistar-Kyoto (WKY), com oito semanas de vida. Estes foram divididos em quatro grupos, seis SHR – Treinados, seis SHR – Sedentários, seis WKY – Treinados, seis WKY – Sedentários. Os animais dos grupos treinados realizaram um protocolo de treinamento físico em esteira rolante durante 13 semanas, realizando sessões de 60 minutos, 5 vezes por semana, a uma intensidade de 55% do VO2 máximo. Nesse mesmo período, em um dia que não era realizado o treinamento físico, eram feitas as coletas de dados da pressão arterial sistólica (PAS) e frequência cardíaca (FC) de todos os animais, por meio da pletismografia caudal. Além dos parâmetros de PAS e FC, foram coletados os dados do teste de tolerância ao esforço físico progressivo, além das análises de genotoxicidade do DNA dos músculos esqueléticos sóleo e plantar. Em relação ao teste de tolerância ao esforço físico progressivo, os animais que realizaram o protocolo de treinamento físico, apresentaram resultados superiores em comparação aos grupos sedentários. Sobre os dados de PAS (pós treinamento) houve diferença estatística em comparação aos grupos WKY e SHR, já em relação aos tratamentos, os animais treinados obtiveram números mais acentuados em comparação aos animais sedentários, isso ocorreu para ambos os grupos. No teste de genotoxicidade dos músculos esqueléticos sóleo e plantar, os resultados mostraram que não houve diferenças entre os grupos. Por fim, podemos concluir que o treinamento físico foi eficaz aumentando a capacidade de esforço físico progressivo, e diminuindo a PAS (dos quais os valores pré estava mais elevados no grupo SHR). Em relação aos resultados de genotoxicidade dos músculos esqueléticos, não houve diferença significativa. Entretanto, como existem outros fatores específicos relacionados a hipertensão arterial e apoptose, antes da submissão do presente estudo para publicação, será realizada a análise de imunohistoquímica, para a quantificação das atividades das proteínas pró e anti apoptóticas, para uma possível validação dos resultados de genotoxicidade.
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    Efeitos comparativos de diferentes protocolos de treinamento físico na massa muscular esquelética de ratos diabéticos: natação e esteira rolante
    (Universidade Federal de São Paulo (UNIFESP), 2015-03-13) Moura, Elizabeth de Orleans Carvalho de [UNIFESP]; Medeiros, Alessandra [UNIFESP]; http://lattes.cnpq.br/0071198026371230; http://lattes.cnpq.br/7179837567280020; Universidade Federal de São Paulo (UNIFESP)
    Diabetes mellitus (DM) is a metabolic syndrome which may affect many organs and systems. Regular physical exercise is associated with attenuation of diabetes complications in people with type 1 DM (DM1). Physical training (PT) has long been the subject of scientific research in the treatment of diabetes . However, there are still few studies comparing the different training protocols available to people with diabetes. The aim of this study was to compare the effects on the skeletal muscle of diabetic rats of aerobic TF performed with the aerobic swimming to TF effects performed on a treadmill. Thus, 42 male Wistar rats were randomized into 4 groups diabetic control (DS), non-diabetic (CS) diabetic trained on the treadmill (DE) and diabetic trained on swimming (DN) . To induce type 1 diabetes, animals received 70 mg / kg of intravenous streptozotocin. The trained groups performed 8 weeks of TF in their respective ergometers at maximum lactate steady state intensity (MLSS). We evaluated the following data: exercise tolerance, MLSS, glycemic control and body weight, water and food intake, excretion of urine and feces, soleus and EDL muscles wet weight, muscle glycogen and the cross-sectional area of soleus and EDL muscles. Data were analyzed using one or two-way repeated way ANOVA with Bonferroni pos hoc comparisons. We found that the glycemic profile in DN group showed the smallest variation between the means throughout the experiment. Only in the last week the DE group increased average compared to DN and CS groups. Regarding body mass variation both TF protocols offered no significant differences. In relation to food and water intake, DS, DN and DE groups showed higher consumption compared to CS group. The trained groupsDN (137.16 ± 16.85) and DE (125.33 ± 21.51) showed a significant increase in water consumption during post-exercise period when compared to DS group (14.10 ± 11 16). Excretion of feces and urine were higher in DN (28.74 ± 4.98; 149.54 ± 31.02) and DE (40.85 ± 14.76; 136.44 ± 31.09) groups when compared to CS (7.45 ± 3.45; 21.9 ± 9.60) and DS (17.67 ± 4.69; 56.45 ± 19.57) groups. At maximal exercise test DE group (27.96 ± 4.53) was larger than DN (23.37 ± 5.46) although both showed higher exercise tolerance in the post-exercise period when compared to the DS group (16.05 ± 3.73). In MLSS, DE group only showed a significant increase when comparing post- versus pre-exercise. There was no statistical difference between TF protocols studied regarding wet weight of soleus and EDL. Regarding cross-sectional area of muscle fibers, only the ED group (3184.49 ± 1018.31; 1898.07 ± 481.54) showed higher cross-sectional area for both soleus and EDL muscles when compared to all CS groups (1039.35 ± 168.98; 819.65 ± 130.15), DS (689.62 ± 54.82; 504.19 ± 174.49) and DN (1110.99 ± 221.27; 702.56 ± 149.19). However, analysis of muscle glycogen in EDL showed that DN and DE groups (1277.0 ± 365.55; 1001.2 ± 288.25) had higher concentrations compared to CS and DS (647.9 ± 150.72; 20.9 ± 83.86), DN being greater than DE. For muscle glycogen of soleus muscle, there was statistical diference (p?0.05) between all groups, being DN and DE groups (813.5 ± 350.65; 696.4 ± 148.05) higher than DS (257.2 ± 95.78).Only DN was higher than CS (452.2 ± 178.94) For soleus muscle, we found a statistical difference between all groups (p = 0.05) Thus, our data suggests that both aerobic TF protocols in animals with DM1offered benefits in aspects such as reduced variation of blood glucose levels, improved resistance to physical exertion, increased cross-sectional area, increase in muscle glycogen concentration and an improvement in MLSS when compared to control animals. Regarding the variables glycemic profile, maximal exercise test, cross-sectional area and MLSS was possible to visualize difference between DN and DE groups. The glycemic profile of DN group showed a small variation between the measurements concerning the trial period although no statistical difference was found. At maximal exercise test DE group animals showed better performance and higher cross-sectional area when compared to DN group. MLSS in the DE group showed improvement in the first half of TF protocol, which can suggest that training on the treadmill was more effective.
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    Efeitos do óleo de peixe sobre indicadores indiretos de lesão e morfologia das fibras musculares em ratos wistar submetidos a treinamento resistido
    (Universidade Federal de São Paulo (UNIFESP), 2018-12-20) Coqueiro, Daniel Pereira [UNIFESP]; Simões, Manuel de Jesus [UNIFESP]; Bueno, Patricia Cincotto dos Santos; http://lattes.cnpq.br/2557791256543812; http://lattes.cnpq.br/5987164343458678; http://lattes.cnpq.br/7423610207242392; Universidade Federal de São Paulo (UNIFESP)
    Introduction: Fish oil rich in omega-3 polyunsaturated fatty acids (PUFA/n3) has been studied for the purpose of reducing levels of inflammation, which are increased under disease conditions or tissue lesions. Objective: To evaluate the effects of fish oil intake on muscle injuries induced by resistance exercise (RE). Methods: Fifty-Six Wistar rats were initially divided into three groups. Control group (Cont), composed of eight animals that did not receive fish oil and did not make RE; Resistance Exercise Group (Ex) composed of 24 animals that performed RE and did not receive fish oil; and Resistance Exercise group and fish oil (ExO) composed of 24 animals that performed RE and received fish oil. The RE was performed in a tank and consisted of vertical jumps from the bottom of the tank to the surface of the water. For the protocol, an additional load was fixed to the thorax of the animals. The animals performed 10 vertical jumps repeated 4 times (series) with 60s intervals between sets, three times a week for 8 weeks. The animals of the EXO Group received 2g/kg/day of fish oil. At the end of the last RE session, the animals receiving fish oil and those not receiving the fish oil were subdivided according to the time of blood collection and withdrawal of the gastrocnemius muscle (12, 24 and 48 hours). Results: The indicators of muscle injury Creatine Kinase (CK) and lactic dehydrogenase (DHL) were lower in the groups that ingested fish oil and belonged to time periods 12, 24, 48 h post RE. The values of Protein C reactive (PCR) and Myoglobin (Mb) were respectively lower in the group analyzed in the period 24 and 12h post RE and that received fish oil. Animals that used fish oil thromped statistically more favorably to dissociation of muscle fibers, presence of inflammatory infiltrate and necrosis.Conclusion: The physical exercise model produced alterations in the indirect serum markers of muscle lesion and morphological alterations, and the fish oil intake decreased the serum levels of these indicators and mitigated the morphological alterations in muscle tissue.
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    Efeitos do treinamento físico aeróbio sobre a resposta à proteína mal enovelada na musculatura esquelética de ratos submetidos à uremia experimental
    (Universidade Federal de São Paulo (UNIFESP), 2016-07-28) Moraes, Wilson Max Almeida Monteiro de [UNIFESP]; Medeiros, Alessandra [UNIFESP]; http://lattes.cnpq.br/0071198026371230; Universidade Federal de São Paulo (UNIFESP)
    The present study tested whether aerobic exercise training (AET) would modulate the unfolded protein response (UPR) in a model of Chronic Kidney Disease (CKD) in rats. Adult Wistar rats were evaluated in 4 groups: control (CS), control trained (CE), and 5/6 nephrectomy sedentary (5/6NxS) or trained (5/6NxE). Exercised rats were submitted to treadmill exercise for 60 min, 5 times/wk for 2 months. We evaluated motor performance (tolerance to exercise in treadmill and rotarod), cross sectional area (AST), gene and protein levels related to UPR, protein synthesis/survive and apoptosis signaling, accumulated misfolded proteins, chymotripsin-like proteasome activity (UPS activity), redox balance and HSPs protein levels in tibialis anterior. Despite the AST were not different between groups, the 5/6NxS presented a reduction in motor performance followed by down regulation in protein synthesis and up regulation of apoptosis signaling, increased UPS activity, misfolded proteins, GRP78, derlin, HSP27 and HSP70 protein levels and ATF4 and GRP78 genes, increased in oxidative damage compared to CS group. In 5/6NxE, we observed restoration in exercise tolerance, accumulated misfolded proteins, UPS activity, protein synthesis and apoptosis signaling, derlin and HSPs protein levels as well as increased in ATF4 and GRP78 genes and GRP78,ATF6? protein levels accompanied by an decrease in oxidative damage and increased catalase and glutathione-peroxidase activities. These results suggest that an UPR is activated in white muscle fibers of CKD rats, independently of atrophy and that AET amplified this response, but prevented accumulated misfolded proteins, promoting reduction in oxidative damage, HSPs protein levels and exercise tolerance.
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    The Effect of the Aerobic Training on Morphological and Histochemical Characteristics of Tibial Anterior Muscle in Rats Fed with High Fat Diet
    (Soc Chilena Anatomia, 2008-12-01) Ciabattari, Olimpia Maria [UNIFESP]; Dâmaso, Ana Raimunda [UNIFESP]; Dal Pai, V; Dal-Pai-Silva, M.; Freitas, I. F.; Universidade Federal de São Paulo (UNIFESP); Univ Western Sao Paulo UNOESTE; Sao Paulo State Univ UNESP
    The aim of this study was to investigate the effect of high fat diet and different frequencies of swimming programs in the tibial anterior muscle in male Wistar rats. In conclussion, the aerobic training during two days/week and five days/week caused injuries in muscle fibers and the high fat diet did not cause statically significant results compared to normal diet.
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    The effects of prenatal and postnatal malnutrition on the morphology, differentiation, and metabolism of skeletal striated muscle tissue in rats
    (Soc Brasil Pediatria, 2008-05-01) Alves, Alessandra Pires [UNIFESP]; Dâmaso, Ana Raimunda [UNIFESP]; Dal Pai, Vitalino; Universidade Federal de São Paulo (UNIFESP); Univ Oeste Paulista Unoeste
    Objective: To study the contractile properties, metabolism and. morphological characteristics of muscles submitted to prenatal and postnatal protein malnutrition.Methods: Animals were distributed into two groups: Control, normoprotein diet (CG; n = 15; 5/5/5), and Malnourished, hypoprotein diet (MG; n = 15; 5/5/5), and examined on the 7th, 14th, and 28th days of the experiment. Total body mass, weight, and the contractile properties and morphology of the anterior tibial muscle were assessed. Several 8 mu m-thick tissue samples were taken from 7, 14, and 28 day old rats and stained with HE or subjected to NADH-TR or m-ATPase (pH = 4.4) techniques.Results: Body and muscle weight were lower in the malnourished group. On the 7th day of malnutrition, muscle samples exhibited fibers with smaller diameter, higher polymorphism and higher endomysial conjunctive tissue content. Histochemical methods were unable to precisely determine the types of fiber present, On the 14th day, there were smaller muscle fibers, more polymorphism, many of them with central nuclei and moderate endomysial conjunctive tissue content. With reference to contractile properties, the m-ATPase reaction identified both slow and fast fibers. the NADH-TR reaction revealed the following types of fiber: slow oxidative (SO), fast oxidative glycolytic (FOG) and fast glycolytic (FG). On the 28th day smaller, bunched muscle fibers varying shapes. All three types of fiber exhibited unclear recognition limits with respect to contraction and metabolism.Conclusion: Our experimental results suggest that, in addition to the reduction in numbers of fibers, malnutrition retards the differentiation of the morphological, metabolic, and contractile characteristics of skeletal muscle fibers in growing rats.
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    Erythropoietin reduces the expression of myostatin in mdx dystrophic mice
    (Assoc Bras Divulg Cientifica, 2014-11-01) Feder, David; Rugollini, M.; Santomauro, A.; Oliveira, Luciano P.; Lioi, V. P.; Santos, Rosangela Aparecida dos; Ferreira, Leonardo G.; Nunes, Maria Tereza; Carvalho, Maria Helena; Delgado, Pilar O.; Carvalho, Alzira A. S.; Fonseca, Fernando Luiz Affonso [UNIFESP]; Fac Med ABC; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)
    Erythropoietin (EPO) has been well characterized as a renal glycoprotein hormone regulating red blood cell production by inhibiting apoptosis of erythrocyte progenitors in hematopoietic tissues. EPO exerts regulatory effects in cardiac and skeletal muscles. Duchenne muscular dystrophy is a lethal degenerative disorder of skeletal and cardiac muscle. in this study, we tested the possible therapeutic beneficial effect of recombinant EPO (rhEPO) in dystrophic muscles in mdx mice. Total strength was measured using a force transducer coupled to a computer. Gene expression for myostatin, transforming growth factor-beta 1 (TGF-beta 1), and tumor necrosis factor-alpha (TNF-alpha) was determined by quantitative real time polymerase chain reaction. Myostatin expression was significantly decreased in quadriceps from mdx mice treated with rhEPO (rhEPO = 0.60 +/- 0.11, control= 1.07 +/- 0.11). On the other hand, rhEPO had no significant effect on the expression of TGF-beta 1 (rhEPO = 0.95 +/- 0.14, control= 1.05 +/- 0.16) and TNF-alpha (rhEPO = 0.73 +/- 0.20, control= 1.01 +/- 0.09). These results may help to clarify some of the direct actions of EPO on skeletal muscle.