Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 16 de 16
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Artigo em Inglês | MEDLINE | ID: mdl-31743617

RESUMO

BACKGROUND: The exercise intolerance in chronic heart failure with reduced ejection fraction (HFrEF) is mostly attributed to alterations in skeletal muscle. However, the mechanisms underlying the skeletal myopathy in patients with HFrEF are not completely understood. We hypothesized that (i) aerobic exercise training (AET) and inspiratory muscle training (IMT) would change skeletal muscle microRNA-1 expression and downstream-associated pathways in patients with HFrEF and (ii) AET and IMT would increase leg blood flow (LBF), functional capacity, and quality of life in these patients. METHODS: Patients age 35 to 70 years, left ventricular ejection fraction (LVEF) ≤40%, New York Heart Association functional classes II-III, were randomized into control, IMT, and AET groups. Skeletal muscle changes were examined by vastus lateralis biopsy. LBF was measured by venous occlusion plethysmography, functional capacity by cardiopulmonary exercise test, and quality of life by Minnesota Living with Heart Failure Questionnaire. All patients were evaluated at baseline and after 4 months. RESULTS: Thirty-three patients finished the study protocol: control (n = 10; LVEF = 25 ± 1%; six males), IMT (n = 11; LVEF = 31 ± 2%; three males), and AET (n = 12; LVEF = 26 ± 2%; seven males). AET, but not IMT, increased the expression of microRNA-1 (P = 0.02; percent changes = 53 ± 17%), decreased the expression of PTEN (P = 0.003; percent changes = -15 ± 0.03%), and tended to increase the p-AKTser473 /AKT ratio (P = 0.06). In addition, AET decreased HDAC4 expression (P = 0.03; percent changes = -40 ± 19%) and upregulated follistatin (P = 0.01; percent changes = 174 ± 58%), MEF2C (P = 0.05; percent changes = 34 ± 15%), and MyoD expression (P = 0.05; percent changes = 47 ± 18%). AET also increased muscle cross-sectional area (P = 0.01). AET and IMT increased LBF, functional capacity, and quality of life. Further analyses showed a significant correlation between percent changes in microRNA-1 and percent changes in follistatin mRNA (P = 0.001, rho = 0.58) and between percent changes in follistatin mRNA and percent changes in peak VO2 (P = 0.004, rho = 0.51). CONCLUSIONS: AET upregulates microRNA-1 levels and decreases the protein expression of PTEN, which reduces the inhibitory action on the PI3K-AKT pathway that regulates the skeletal muscle tropism. The increased levels of microRNA-1 also decreased HDAC4 and increased MEF2c, MyoD, and follistatin expression, improving skeletal muscle regeneration. These changes associated with the increase in muscle cross-sectional area and LBF contribute to the attenuation in skeletal myopathy, and the improvement in functional capacity and quality of life in patients with HFrEF. IMT caused no changes in microRNA-1 and in the downstream-associated pathway. The increased functional capacity provoked by IMT seems to be associated with amelioration in the respiratory function instead of changes in skeletal muscle. ClinicalTrials.gov (Identifier: NCT01747395).

2.
J Appl Physiol (1985) ; 122(4): 817-827, 2017 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-28104751

RESUMO

We have recently demonstrated that NADPH oxidase hyperactivity, NF-κB activation, and increased p38 phosphorylation lead to atrophy of glycolytic muscle in heart failure (HF). Aerobic exercise training (AET) is an efficient strategy to counteract skeletal muscle atrophy in this syndrome. Therefore, we tested whether AET would regulate muscle redox balance and protein degradation by decreasing NADPH oxidase hyperactivity and reestablishing NF-κB signaling, p38 phosphorylation, and proteasome activity in plantaris muscle of myocardial infarcted-induced HF (MI) rats. Thirty-two male Wistar rats underwent MI or fictitious surgery (SHAM) and were randomly assigned into untrained (UNT) and trained (T; 8 wk of AET on treadmill) groups. AET prevented HF signals and skeletal muscle atrophy in MI-T, which showed an improved exercise tolerance, attenuated cardiac dysfunction and increased plantaris fiber cross-sectional area. To verify the role of inflammation and redox imbalance in triggering protein degradation, circulating TNF-α levels, NADPH oxidase profile, NF-κB signaling, p38 protein levels, and proteasome activity were assessed. MI-T showed a reduced TNF-α levels, NADPH oxidase activity, and Nox2 mRNA expression toward SHAM-UNT levels. The rescue of NADPH oxidase activity induced by AET in MI rats was paralleled by reducing nuclear binding activity of the NF-κB, p38 phosphorylation, atrogin-1, mRNA levels, and 26S chymotrypsin-like proteasome activity. Taken together our data provide evidence for AET improving plantaris redox homeostasis in HF associated with a decreased NADPH oxidase, redox-sensitive proteins activation, and proteasome hyperactivity further preventing atrophy. These data reinforce the role of AET as an efficient therapy for muscle wasting in HF.NEW & NOTEWORTHY This study demonstrates, for the first time, the contribution of aerobic exercise training (AET) in decreasing muscle NADPH oxidase activity associated with reduced reactive oxygen species production and systemic inflammation, which diminish NF-κB overactivation, p38 phosphorylation, and ubiquitin proteasome system hyperactivity. These molecular changes counteract plantaris atrophy in trained myocardial infarction-induced heart failure rats. Our data provide new evidence into how AET may regulate protein degradation and thus prevent skeletal muscle atrophy.


Assuntos
Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatologia , NADPH Oxidases/metabolismo , Condicionamento Físico Animal/fisiologia , Animais , Modelos Animais de Doenças , Teste de Esforço/métodos , Coração/fisiologia , Masculino , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/fisiologia , Atrofia Muscular/metabolismo , Atrofia Muscular/fisiopatologia , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/fisiopatologia , NF-kappa B/metabolismo , Oxirredução , Fosforilação/fisiologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise , Ratos , Ratos Wistar , Transdução de Sinais/fisiologia , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
3.
Mayo Clin Proc ; 91(5): 575-86, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27040087

RESUMO

OBJECTIVE: To examine whether combined testosterone replacement and exercise training (ET) therapies would potentiate the beneficial effects of isolated therapies on neurovascular control and muscle wasting in patients with heart failure (HF) with testosterone deficiency. PATIENTS AND METHODS: From January 10, 2010, through July 25, 2013, 39 male patients with HF, New York Heart Association functional class III, total testosterone level less than 249 ng/dL (to convert to nmol/L, multiply by .03467), and free testosterone level less than 131 pmol/L were randomized to training (4-month cycloergometer training), testosterone (intramuscular injection of testosterone undecylate for 4 months), and training + testosterone groups. Muscle sympathetic nerve activity was measured using microneurography, forearm blood flow using plethysmography, body composition using dual X-ray absorptiometry, and functional capacity using cardiopulmonary test. Skeletal muscle biopsy was performed in the vastus lateralis. RESULTS: Muscle sympathetic nerve activity decreased in ET groups (training, P<.01; training + testosterone, P<.01), whereas no changes were observed in the testosterone group (P=.89). Forearm blood flow was similar in all groups. Lean mass increased in ET groups (training, P<.01; training + testosterone, P<.01), whereas lean mass decreased in the testosterone group (P<.01). The response of cross-sectional area of type I (P<.01) and type II (P<.05) fibers increased in the training + testosterone group as compared with the isolated testosterone group. CONCLUSION: Our findings provide evidence for a superior effect of combined ET and testosterone replacement therapies on muscle sympathetic nerve activity, muscle wasting, and functional capacity in patients with HF with testosterone deficiency.


Assuntos
Exercício/fisiologia , Insuficiência Cardíaca/terapia , Terapia de Reposição Hormonal , Músculo Esquelético/efeitos dos fármacos , Testosterona/administração & dosagem , Absorciometria de Fóton , Análise de Variância , Androgênios/administração & dosagem , Androgênios/deficiência , Androgênios/fisiologia , Biópsia , Composição Corporal , Brasil , Terapia Combinada , Teste de Esforço , Antebraço/irrigação sanguínea , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/complicações , Humanos , Injeções Intramusculares , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Consumo de Oxigênio , Pletismografia , Prognóstico , Estudos Prospectivos , Músculo Quadríceps/metabolismo , Músculo Quadríceps/patologia , Qualidade de Vida , Sistema Nervoso Simpático/fisiopatologia , Testosterona/deficiência , Testosterona/fisiologia
4.
Int J Cardiol ; 214: 137-47, 2016 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-27060274

RESUMO

BACKGROUND: Exercise intolerance is one of the main clinical symptoms of heart failure (HF) and is associated with skeletal muscle wasting due to an imbalance between proteolysis and protein synthesis. In this study, we tested whether aerobic exercise training (AET) would counteract skeletal muscle atrophy by activating IGF-I/Akt/mTOR pathway in HF mice. METHODS: Sympathetic hyperactivity induced HF mice were assigned into 8-week moderate intensity AET. Untrained wild type and HF mice were used as control. Soleus cross sectional area was evaluated by histochemistry and motor performance by rotarod. 26S proteasome activity was assessed by fluorimetric assay, and components of IGF-I/Akt/mTOR pathway or myostatin pathway by qRT-PCR or immunoblotting. A different subset of mice was used to evaluate the relative contribution of mTOR inhibition (rapamycin) or activation (leucine) on AET-induced changes in muscle mass regulation. RESULTS: AET prevented exercise intolerance and impaired motor performance in HF mice. These effects were associated with attenuation of soleus atrophy. Rapamycin treatment precluded AET effects on soleus mass in HF mice suggesting the involvement of IGF signaling pathway in this response. In fact, AET increased IGF-I Ea and IGF-I Pan mRNA levels, while it reduced myostatin and Smad2 mRNA levels in HF mice. At protein levels, AET prevented reduced expression levels of IGF-I, pAkt (at basal state), as well as, p4E-BP1 and pP70(S6K) (leucine-stimulated state) in HF mice. Additionally, AET prevented 26S proteasome hyperactivity in HF mice. CONCLUSIONS: Taken together, our data provide evidence for AET-induced activation of IGF-I/Akt/mTOR signaling pathway counteracting HF-induced muscle wasting.


Assuntos
Insuficiência Cardíaca/metabolismo , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Condicionamento Físico Animal/fisiologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Insuficiência Cardíaca/terapia , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Atrofia Muscular/prevenção & controle , Condicionamento Físico Animal/métodos , RNA Mensageiro/metabolismo , Transdução de Sinais/fisiologia
5.
PLoS One ; 10(8): e0134844, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26302153

RESUMO

Metabolic syndrome is a cluster of metabolic risk factors such as obesity, diabetes and cardiovascular diseases. Mitochondria is the main site of ATP production and its dysfunction leads to decreased oxidative phosphorylation, resulting in lipid accumulation and insulin resistance. Our group has demonstrated that kinins can modulate glucose and lipid metabolism as well as skeletal muscle mass. By using B2 receptor knockout mice (B2R-/-) we investigated whether kinin action affects weight gain and physical performance of the animals. Our results show that B2R-/- mice are resistant to high fat diet-induced obesity, have higher glucose tolerance as well as increased mitochondrial mass. These features are accompanied by higher energy expenditure and a lower feed efficiency associated with an increase in the proportion of type I fibers and intermediary fibers characterized by higher mitochondrial content and increased expression of genes related to oxidative metabolism. Additionally, the increased percentage of oxidative skeletal muscle fibers and mitochondrial apparatus in B2R-/- mice is coupled with a higher aerobic exercise performance. Taken together, our data give support to the involvement of kinins in skeletal muscle fiber type distribution and muscle metabolism, which ultimately protects against fat-induced obesity and improves aerobic exercise performance.


Assuntos
Músculo Esquelético/metabolismo , Condicionamento Físico Animal/fisiologia , Receptor B2 da Bradicinina/fisiologia , Animais , Dieta Hiperlipídica , Expressão Gênica/fisiologia , Teste de Tolerância a Glucose , Insulina/sangue , Leptina/sangue , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Esquelético/fisiologia , Consumo de Oxigênio/fisiologia
6.
Mediators Inflamm ; 2014: 326803, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24987195

RESUMO

Glucose and glutamine are important energetic and biosynthetic nutrients for T and B lymphocytes. These cells consume both nutrients at high rates in a function-dependent manner. In other words, the pathways that control lymphocyte function and survival directly control the glucose and glutamine metabolic pathways. Therefore, lymphocytes in different functional states reprogram their glucose and glutamine metabolism to balance their requirement for ATP and macromolecule production. The tight association between metabolism and function in these cells was suggested to introduce the possibility of several pathologies resulting from the inability of lymphocytes to meet their nutrient demands under a given condition. In fact, disruptions in lymphocyte metabolism and function have been observed in different inflammatory, metabolic, and autoimmune pathologies. Regular physical exercise and physical activity offer protection against several chronic pathologies, and this benefit has been associated with the anti-inflammatory and immunomodulatory effects of exercise/physical activity. Chronic exercise induces changes in lymphocyte functionality and substrate metabolism. In the present review, we discuss whether the beneficial effects of exercise on lymphocyte function in health and disease are associated with modulation of the glucose and glutamine metabolic pathways.


Assuntos
Exercício/fisiologia , Glucose/metabolismo , Glutamina/metabolismo , Linfócitos/metabolismo , Animais , Humanos , Condicionamento Físico Animal
7.
J Strength Cond Res ; 28(11): 3215-23, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24832980

RESUMO

Concurrent training (CT) seems to impair training-induced muscle hypertrophy. This study compared the effects of CT, strength training (ST) and interval training (IT) on the muscle fiber cross-sectional area (CSA) response, and on the expression of selected genes involved in the myostatin (MSTN) signaling mRNA levels. Thirty-seven physically active men were randomly divided into 4 groups: CT (n = 11), ST (n = 11), IT (n = 8), and control group (C) (n = 7) and underwent an 8-week training period. Vastus lateralis biopsy muscle samples were obtained at baseline and 48 hours after the last training session. Muscle fiber CSA, selected genes expression, and maximum dynamic ST (1 repetition maximum) were evaluated before and after training. Type IIa and type I muscle fiber CSA increased from pre- to posttest only in the ST group (17.08 and 17.9%, respectively). The SMAD-7 gene expression significantly increased at the posttest in the ST (53.9%) and CT groups (39.3%). The MSTN and its regulatory genes ActIIb, FLST-3, FOXO-3a, and GASP-1 mRNA levels remained unchanged across time and groups. One repetition maximum increased from pre- to posttest in both the ST and CT groups (ST = 18.5%; CT = 17.6%). Our findings are suggestive that MSTN and their regulatory genes at transcript level cannot differentiate muscle fiber CSA responses between CT and ST regimens in humans.


Assuntos
Expressão Gênica , Miostatina/metabolismo , Músculo Quadríceps/metabolismo , Treinamento de Resistência , Corrida/fisiologia , Adolescente , Adulto , Teste de Esforço , Proteína Forkhead Box O3 , Fatores de Transcrição Forkhead/genética , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Masculino , Fibras Musculares de Contração Rápida/citologia , Fibras Musculares de Contração Lenta/citologia , Miostatina/genética , Consumo de Oxigênio , Condicionamento Físico Humano/métodos , Condicionamento Físico Humano/fisiologia , Proteínas/genética , Músculo Quadríceps/citologia , RNA Mensageiro/metabolismo , Transdução de Sinais/genética , Proteína Smad7/genética , Adulto Jovem
8.
J Cell Mol Med ; 18(6): 1087-97, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24629015

RESUMO

Skeletal myopathy is a hallmark of heart failure (HF) and has been associated with a poor prognosis. HF and other chronic degenerative diseases share a common feature of a stressed system: sympathetic hyperactivity. Although beneficial acutely, chronic sympathetic hyperactivity is one of the main triggers of skeletal myopathy in HF. Considering that ß2 -adrenoceptors mediate the activity of sympathetic nervous system in skeletal muscle, we presently evaluated the contribution of ß2 -adrenoceptors for the morphofunctional alterations in skeletal muscle and also for exercise intolerance induced by HF. Male WT and ß2 -adrenoceptor knockout mice on a FVB genetic background (ß2 KO) were submitted to myocardial infarction (MI) or SHAM surgery. Ninety days after MI both WT and ß2 KO mice presented to cardiac dysfunction and remodelling accompanied by significantly increased norepinephrine and epinephrine plasma levels, exercise intolerance, changes towards more glycolytic fibres and vascular rarefaction in plantaris muscle. However, ß2 KO MI mice displayed more pronounced exercise intolerance and skeletal myopathy when compared to WT MI mice. Skeletal muscle atrophy of infarcted ß2 KO mice was paralleled by reduced levels of phosphorylated Akt at Ser 473 while increased levels of proteins related with the ubiquitin--proteasome system, and increased 26S proteasome activity. Taken together, our results suggest that lack of ß2 -adrenoceptors worsen and/or anticipate the skeletal myopathy observed in HF.


Assuntos
Insuficiência Cardíaca/complicações , Músculo Esquelético/patologia , Atrofia Muscular/etiologia , Infarto do Miocárdio/complicações , Receptores Adrenérgicos beta 2/fisiologia , Animais , Ecocardiografia , Insuficiência Cardíaca/fisiopatologia , Masculino , Camundongos , Camundongos Knockout , Músculo Esquelético/metabolismo , Atrofia Muscular/patologia , Infarto do Miocárdio/fisiopatologia , Condicionamento Físico Animal , Complexo de Endopeptidases do Proteassoma , Transdução de Sinais , Ubiquitina/metabolismo
9.
PLoS One ; 7(8): e41701, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22870245

RESUMO

BACKGROUND: Heart failure (HF) is known to lead to skeletal muscle atrophy and dysfunction. However, intracellular mechanisms underlying HF-induced myopathy are not fully understood. We hypothesized that HF would increase oxidative stress and ubiquitin-proteasome system (UPS) activation in skeletal muscle of sympathetic hyperactivity mouse model. We also tested the hypothesis that aerobic exercise training (AET) would reestablish UPS activation in mice and human HF. METHODS/PRINCIPAL FINDINGS: Time-course evaluation of plantaris muscle cross-sectional area, lipid hydroperoxidation, protein carbonylation and chymotrypsin-like proteasome activity was performed in a mouse model of sympathetic hyperactivity-induced HF. At the 7(th) month of age, HF mice displayed skeletal muscle atrophy, increased oxidative stress and UPS overactivation. Moderate-intensity AET restored lipid hydroperoxides and carbonylated protein levels paralleled by reduced E3 ligases mRNA levels, and reestablished chymotrypsin-like proteasome activity and plantaris trophicity. In human HF (patients randomized to sedentary or moderate-intensity AET protocol), skeletal muscle chymotrypsin-like proteasome activity was also increased and AET restored it to healthy control subjects' levels. CONCLUSIONS: Collectively, our data provide evidence that AET effectively counteracts redox imbalance and UPS overactivation, preventing skeletal myopathy and exercise intolerance in sympathetic hyperactivity-induced HF in mice. Of particular interest, AET attenuates skeletal muscle proteasome activity paralleled by improved aerobic capacity in HF patients, which is not achieved by drug treatment itself. Altogether these findings strengthen the clinical relevance of AET in the treatment of HF.


Assuntos
Terapia por Exercício , Proteínas Musculares/metabolismo , Atrofia Muscular , Estresse Oxidativo , Condicionamento Físico Animal , Complexo de Endopeptidases do Proteassoma/metabolismo , Ubiquitina/metabolismo , Idoso , Idoso de 80 Anos ou mais , Animais , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Humanos , Peroxidação de Lipídeos/genética , Masculino , Camundongos , Camundongos Knockout , Proteínas Musculares/genética , Atrofia Muscular/etiologia , Atrofia Muscular/genética , Atrofia Muscular/metabolismo , Atrofia Muscular/fisiopatologia , Atrofia Muscular/terapia , Complexo de Endopeptidases do Proteassoma/genética , Ubiquitina/genética
10.
J Appl Physiol (1985) ; 112(11): 1839-46, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22461440

RESUMO

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, and CSA. Muscle RING finger-1 mRNA expression was increased in 8-wk-trained mice. Accordingly, elevated 26S proteasome activity was observed in the 8-wk-trained group, without accumulation of ubiquitinated or carbonylated proteins. In addition, calpain abundance was increased by 8 wk of AET, whereas no difference was observed in its endogenous inhibitor calpastatin. Taken together, our findings indicate that skeletal muscle enhancements, as evidenced by increased running capacity, plantaris capillarization, and CSA, occurred in spite of the upregulated UPS and calpain system, suggesting that overactivation of skeletal muscle proteolytic systems is not restricted to atrophying states. Our data provide evidence for the contribution of the UPS and calpain system to metabolic turnover of myofibrillar proteins and skeletal muscle adaptations to AET.


Assuntos
Calpaína/biossíntese , Músculo Esquelético/metabolismo , Condicionamento Físico Animal/fisiologia , Complexo de Endopeptidases do Proteassoma/biossíntese , Ubiquitina/biossíntese , Regulação para Cima/fisiologia , Animais , Teste de Esforço/métodos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/enzimologia , Condicionamento Físico Animal/métodos
11.
Cell Biochem Funct ; 28(4): 266-73, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20517889

RESUMO

Active lymphocytes (LY) and macrophages (MPhi) 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 MPhi, 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.


Assuntos
Artrite Experimental/metabolismo , Linfócitos/metabolismo , Macrófagos/metabolismo , Condicionamento Físico Animal , Animais , Artrite Experimental/induzido quimicamente , Artrite Experimental/prevenção & controle , Bovinos , Colágeno Tipo II/toxicidade , Corticosterona/sangue , Feminino , Glucose/metabolismo , Glutamina/metabolismo , Interleucina-2/sangue , Linfócitos/imunologia , Linfócitos/fisiologia , Macrófagos/imunologia , Macrófagos/fisiologia , Progesterona/sangue , Ratos , Ratos Wistar
12.
Mediators Inflamm ; 2010: 364290, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21234393

RESUMO

In lymphocytes (LY), the well-documented antiproliferative effects of IFN-α are associated with inhibition of protein synthesis, decreased amino acid incorporation, and cell cycle arrest. However, the effects of this cytokine on the metabolism of glucose and glutamine in these cells have not been well investigated. Thus, mesenteric and spleen LY of male Wistar rats were cultured in the presence or absence of IFN-α, and the changes on glucose and glutamine metabolisms were investigated. The reduced proliferation of mesenteric LY was accompanied by a reduction in glucose total consumption (35%), aerobic glucose metabolism (55%), maximal activity of glucose-6-phosphate dehydrogenase (49%), citrate synthase activity (34%), total glutamine consumption (30%), aerobic glutamine consumption (20.3%) and glutaminase activity (56%). In LY isolated from spleen, IFNα also reduced the proliferation and impaired metabolism. These data demonstrate that in LY, the antiproliferative effects of IFNα are associated with a reduction in glucose and glutamine metabolisms.


Assuntos
Glucose/metabolismo , Glutamina/metabolismo , Fatores Imunológicos/farmacologia , Interferon-alfa/farmacologia , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Fatores Imunológicos/imunologia , Interferon-alfa/imunologia , Linfonodos/citologia , Linfócitos/citologia , Masculino , Mesentério/citologia , Ratos , Ratos Wistar , Baço/citologia
13.
J Appl Physiol (1985) ; 106(5): 1631-40, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19179649

RESUMO

Sympathetic hyperactivity (SH) is a hallmark of heart failure (HF), and several lines of evidence suggest that SH contributes to HF-induced skeletal myopathy. However, little is known about the influence of SH on skeletal muscle morphology and metabolism in a setting of developing HF, taking into consideration muscles with different fiber compositions. The contribution of SH on exercise tolerance and skeletal muscle morphology and biochemistry was investigated in 3- and 7-mo-old mice lacking both alpha(2A)- and alpha(2C)-adrenergic receptor subtypes (alpha(2A)/alpha(2C)ARKO mice) that present SH with evidence of HF by 7 mo. To verify whether exercise training (ET) would prevent skeletal muscle myopathy in advanced-stage HF, alpha(2A)/alpha(2C)ARKO mice were exercised from 5 to 7 mo of age. At 3 mo, alpha(2A)/alpha(2C)ARKO mice showed no signs of HF and preserved exercise tolerance and muscular norepinephrine with no changes in soleus morphology. In contrast, plantaris muscle of alpha(2A)/alpha(2C)ARKO mice displayed hypertrophy and fiber type shift (IIA --> IIX) paralleled by capillary rarefaction, increased hexokinase activity, and oxidative stress. At 7 mo, alpha(2A)/alpha(2C)ARKO mice displayed exercise intolerance and increased muscular norepinephrine, muscular atrophy, capillary rarefaction, and increased oxidative stress. ET reestablished alpha(2A)/alpha(2C)ARKO mouse exercise tolerance to 7-mo-old wild-type levels and prevented muscular atrophy and capillary rarefaction associated with reduced oxidative stress. Collectively, these data provide direct evidence that SH is a major factor contributing to skeletal muscle morphological changes in a setting of developing HF. ET prevented skeletal muscle myopathy in alpha(2A)/alpha(2C)ARKO mice, which highlights its importance as a therapeutic tool for HF.


Assuntos
Insuficiência Cardíaca/patologia , Músculo Esquelético/patologia , Condicionamento Físico Animal/fisiologia , Sistema Nervoso Simpático/fisiopatologia , Animais , Capilares/patologia , Modelos Animais de Doenças , Tolerância ao Exercício/fisiologia , Insuficiência Cardíaca/fisiopatologia , Hipertrofia/metabolismo , Hipertrofia/patologia , Masculino , Camundongos , Camundongos Congênicos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Atrofia Muscular/prevenção & controle , Norepinefrina/metabolismo , Estresse Oxidativo/fisiologia , Receptores Adrenérgicos alfa 2/deficiência , Receptores Adrenérgicos alfa 2/genética , Receptores Adrenérgicos alfa 2/metabolismo
14.
In. Krieger, José Eduardo. Bases moleculares das Doenças Cardiovasculares: a integração entre a pesquisa e a prática clínica. São Paulo, Atheneu, 2008. p.281-295.
Monografia em Português | LILACS | ID: lil-511095
15.
An. acad. bras. ciênc ; 78(3): 485-503, Sept. 2006. ilus, tab
Artigo em Inglês | LILACS | ID: lil-433716

RESUMO

A insuficiência cardíaca (IC) é a via final comum da maioria das doenças cardiovasculares e uma das maiores causas de morbi-mortalidade. O desenvolvimento do estágio final da IC freqüentemente envolve um insulto inicial do miocárdio, reduzindo o débito cardíaco e levando ao aumento compensatório da atividade do sistema nervoso simpático (SNS). Existem evidências de que apesar da exposição aguda ser benéfica, exposições crônicas a elevadas concentrações de catecolaminas, liberadas pelo terminal nervoso simpático e pela glândula adrenal, são tóxicas ao tecido cardíaco e levam a deterioração da função cardíaca. Em nível molecular observa-se que a hiperatividade do SNS está associada a alterações na sinalização intracelular mediada pelos receptores beta-adrenérgicos. Sabe-se que tanto a densidade como a função dos receptores beta-adrenérgicos estão diminuídas na IC, assim como outros mecanismos intracelulares subjacentes à estimulação da via receptores beta-adrenérgicos. Nesta revisão, apresentaremos uma breve descrição da via de sinalização dos receptores beta-adrenérgicos no coração normal e as conseqüências da hiperatividade do SNS na IC. Daremos ênfase ao potencial miopático de diversos componentes da cascata de sinalização dos receptores beta-adrenérgicos discutindo estudos realizados com animais geneticamente modificados. Finalmente, discorreremos sobre o impacto clínico do conhecimento dos polimorfismos para o gene do receptor beta-adrenérgico para um melhor entendimento da progressão da IC.


Assuntos
Animais , Humanos , Camundongos , Baixo Débito Cardíaco/fisiopatologia , /fisiologia , Transdução de Sinais/fisiologia , Modelos Animais de Doenças , Progressão da Doença , Polimorfismo Genético , Receptores Adrenérgicos beta 1/genética , Receptores Adrenérgicos beta 1/fisiologia , /genética
16.
An Acad Bras Cienc ; 78(3): 485-503, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16936938

RESUMO

Heart failure (HF) is a common endpoint for many forms of cardiovascular disease and a significant cause of morbidity and mortality. The development of end-stage HF often involves an initial insult to the myocardium that reduces cardiac output and leads to a compensatory increase in sympathetic nervous system activity. Acutely, the sympathetic hyperactivity through the activation of beta-adrenergic receptors increases heart rate and cardiac contractility, which compensate for decreased cardiac output. However, chronic exposure of the heart to elevated levels of catecholamines released from sympathetic nerve terminals and the adrenal gland may lead to further pathologic changes in the heart, resulting in continued elevation of sympathetic tone and a progressive deterioration in cardiac function. On a molecular level, altered beta-adrenergic receptor signaling plays a pivotal role in the genesis and progression of HF. beta-adrenergic receptor number and function are decreased, and downstream mechanisms are altered. In this review we will present an overview of the normal beta-adrenergic receptor pathway in the heart and the consequences of sustained adrenergic activation in HF. The myopathic potential of individual components of the adrenergic signaling will be discussed through the results of research performed in genetic modified animals. Finally, we will discuss the potential clinical impact of beta-adrenergic receptor gene polymorphisms for better understanding the progression of HF.


Assuntos
Baixo Débito Cardíaco/fisiopatologia , Receptores Adrenérgicos beta 2/fisiologia , Transdução de Sinais/fisiologia , Animais , Modelos Animais de Doenças , Progressão da Doença , Humanos , Camundongos , Polimorfismo Genético , Receptores Adrenérgicos beta 1/genética , Receptores Adrenérgicos beta 1/fisiologia , Receptores Adrenérgicos beta 2/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA