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1.
Life Sci ; 221: 224-232, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30771314

RESUMO

AIM: Investigate the effects of moderate continuous aerobic exercise (MCAE) on the inflammatory cytokine profile and expression of lipolytic and thermogenic genes in ß1-AR-/- mice adipose tissue. MAIN METHODS: Four- to five-month-old male wild type (WT) and ß1-AR-/- mice were divided into groups: WT control (WTc) and trained (WTt); and ß1-AR-/- control (ß1-AR-/-c) and trained (ß1-AR-/-t). Animals from trained groups were submitted to a MCAE regimen (60 min/day; 60% of maximal speed, 5 days/week) on a treadmill, for 8 weeks. After euthanasia, white epididymal (eWAT) and inguinal (iWAT) and brown (BAT) adipose tissues were dissected and used to determine: adiposity index; adipocyte histomorphometry; cytokine concentration; and gene expression. The content of fat, protein and water of the empty carcass was determined. KEY FINDINGS: MCAE reduced body weight, fat mass as well as iWAT and BAT adipocyte area in ß1-AR-/- animals. Aerobic exercise also diminished the concentrations of pro-inflammatory (IL-12p70, TNF-α, IL-6) and anti-inflammatory (IL-10) cytokines in adipose tissue (iWAT, eWAT or BAT) of ß1-AR-/- mice. However, MCAE had no effect on the expression lipolytic and thermogenic genes in ß1-AR-/- mice adipose tissue. SIGNIFICANCE: Alongside reductions in body weight, fat mass and adipocyte area eight weeks of MCAE improves the profile of inflammatory cytokines in ß1-AR-/- mice adipose tissue, despite no change in Lipolytic and thermogenic gene expression.


Assuntos
Tecido Adiposo/metabolismo , Citocinas/metabolismo , Condicionamento Físico Animal/fisiologia , Adipócitos/metabolismo , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Adiposidade/fisiologia , Animais , Peso Corporal , Inflamação/metabolismo , Lipólise/genética , Masculino , Camundongos , Camundongos Knockout , Obesidade , Receptores Adrenérgicos beta/genética , Termogênese/genética , Transcriptoma
2.
In. Negrão, Carlos Eduardo; Pereira-Barretto, Antônio Carlos; Rondon, Maria Urbana Pinto Brandão. Cardiologia do exercício: do atleta ao cardiopata / Exercise cardiology: from athlete to heart disease. São Paulo, Manole, 4ª; 2019. p.404-421.
Monografia em Português | LILACS | ID: biblio-1015713
3.
Int. j. cardiovasc. sci. (Impr.) ; 31(6): 610-618, nov.- dez. 2018. tab
Artigo em Inglês | LILACS | ID: biblio-979902

RESUMO

Background: Type 1 diabetes mellitus (DM1) can cause damage to several physiological systems.Objectives: To compare and characterize the effects of aerobic exercise training (ET) performed by swimming with those of ET performed on a treadmill on the skeletal muscle and heart of rats with DM1. Methods: 41 male Wistar rats were randomized into four groups: nondiabetic control (CTR), diabetic control (DMC), diabetic trained on the treadmill (DMT), and diabetic trained by swimming (DMS). The trained groups performed aerobic exercise training for 8 weeks, 5 times a week, 60 min per day. Exercise tolerance, blood glucose, body weight, wet weight of the skeletal muscles and left ventricle (LV), muscle glycogen, cross-sectional area of skeletal muscles, and cross-sectional diameter and collagen volume fraction of the LV were evaluated.Results: The results were expressed as mean ± standard deviation of the mean and submitted to two-way ANOVA with post-hoc Bonferroni test. Aerobic ET protocols applied to animals with DM1, regardless of the ergometer, showed satisfactory results (p < 0.05) when compared to the control groups: improved exercise tolerance, increased glycogen content of the soleus and extensor digitorum longus (EDL) muscles and increased cross-sectional diameter of the left ventricular cardiomyocytes. In some variables, such as exercise tolerance and cross-sectional area of the soleus and EDL muscles, DMT showed better results than DMS (p < 0.05). On the other hand, DMS showed increased cross-sectional diameter of cardiomyocytes when compared with the DMT group. Conclusion: Both aerobic ET protocols offered benefits to animals with diabetes; however, due to the specific characteristics of each modality, different physiological adaptations were observed between the trained groups


Assuntos
Animais , Ratos , Natação , Exercício , Ratos Wistar , Diabetes Mellitus , Teste de Esforço , Peso Corporal , Análise Estatística , Músculo Esquelético , Protocolos , Modelos Animais , Miócitos Cardíacos/fisiologia , Índice Glicêmico , Esforço Físico
4.
Arq. bras. cardiol ; 110(3): 256-262, Mar. 2018. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-888032

RESUMO

Abstract Background: The lack of cardiac β1-adrenergic receptors (β1-AR) negatively affects the regulation of both cardiac inotropy and lusitropy, leading, in the long term, to heart failure (HF). Moderate-intensity aerobic exercise (MCAE) is recommended as an adjunctive therapy for patients with HF. Objective: We tested the effects of MCAE on the contractile properties of left ventricular (LV) myocytes from β1 adrenergic receptor knockout (β1ARKO) mice. Methods: Four- to five-month-old male wild type (WT) and β1ARKO mice were divided into groups: WT control (WTc) and trained (WTt); and β1ARKO control (β1ARKOc) and trained (β1ARKOt). Animals from trained groups were submitted to a MCAE regimen (60 min/day; 60% of maximal speed, 5 days/week) on a treadmill, for 8 weeks. P ≤ 0.05 was considered significant in all comparisons. Results: The β1ARKO and exercised mice exhibited a higher (p < 0.05) running capacity than WT and sedentary ones, respectively. The β1ARKO mice showed higher body (BW), heart (HW) and left ventricle (LVW) weights, as well as the HW/BW and LVW/BW than WT mice. However, the MCAE did not affect these parameters. Left ventricular myocytes from β1ARKO mice showed increased (p < 0.05) amplitude and velocities of contraction and relaxation than those from WT. In addition, MCAE increased (p < 0.05) amplitude and velocities of contraction and relaxation in β1ARKO mice. Conclusion: MCAE improves myocyte contractility in the left ventricle of β1ARKO mice. This is evidence to support the therapeutic value of this type of exercise training in the treatment of heart diseases involving β1-AR desensitization or reduction.


Resumo Fundamento: A falta de receptores β1-adrenérgicos (β1-AR) cardíacos afeta negativamente a regulação de inotropismo e lusitropismo cardíacos, levando, no longo prazo, a insuficiência cardíaca (IC). Recomenda-se exercício aeróbico contínuo de intensidade moderada (EACM) como adjuvante no tratamento de pacientes com IC. Objetivo: Testar os efeitos do EACM nas propriedades contráteis de miócitos do ventrículo esquerdo (VE) de camundongos com nocaute para o receptor β1-adrenérgico (β1ARKO). Método: Camundongos machos com 4 a 5 meses de idade, wild-type (WT) e β1ARKO foram divididos em grupos: WT controle (WTc) e treinado (WTt); e β1ARKO controle (β1ARKOc) e treinado (β1ARKOt). Os grupos treinados foram submetidos a regime de EACM (60 min/dia; 60% da velocidade máxima, 5 dias/semana) em esteira rolante, por 8 semanas. Adotou-se P ≤ 0,05 como nível de significância em todas as comparações. Resultados: Os animais β1ARKO (β1ARKOc + β1ARKOt) correram uma distância maior do que os animais WT (WTc + WTt) (p < 0,05). Os camundongos β1ARKO apresentaram maiores pesos corporal (PC), do coração (PCo) e do ventrículo esquerdo (PVE), assim como PCo/PC e PVE/PC do que os camundongos WT. Entretanto, o EACM não afetou tais parâmetros. Os miócitos do VE de camundongos β1ARKO apresentaram maiores (p < 0,05) amplitude e velocidades de contração e relaxamento do que os dos camundongos WT. Além disso, o EACM aumentou (p < 0,05) a amplitude e as velocidades de contração e relaxamento nos camundongos β1ARKO. Conclusão: O EACM melhora a contratilidade do miócito do VE de camundongos β1ARKO. Tal achado confirma o valor terapêutico desse tipo de treinamento físico para o tratamento de doenças cardíacas envolvendo dessensibilização ou redução de β1-AR.

5.
Arq Bras Cardiol ; 110(3): 256-262, 2018 Mar.
Artigo em Português, Inglês | MEDLINE | ID: mdl-29466489

RESUMO

BACKGROUND: The lack of cardiac ß1-adrenergic receptors (ß1-AR) negatively affects the regulation of both cardiac inotropy and lusitropy, leading, in the long term, to heart failure (HF). Moderate-intensity aerobic exercise (MCAE) is recommended as an adjunctive therapy for patients with HF. OBJECTIVE: We tested the effects of MCAE on the contractile properties of left ventricular (LV) myocytes from ß1 adrenergic receptor knockout (ß1ARKO) mice. METHODS: Four- to five-month-old male wild type (WT) and ß1ARKO mice were divided into groups: WT control (WTc) and trained (WTt); and ß1ARKO control (ß1ARKOc) and trained (ß1ARKOt). Animals from trained groups were submitted to a MCAE regimen (60 min/day; 60% of maximal speed, 5 days/week) on a treadmill, for 8 weeks. P ≤ 0.05 was considered significant in all comparisons. RESULTS: The ß1ARKO and exercised mice exhibited a higher (p < 0.05) running capacity than WT and sedentary ones, respectively. The ß1ARKO mice showed higher body (BW), heart (HW) and left ventricle (LVW) weights, as well as the HW/BW and LVW/BW than WT mice. However, the MCAE did not affect these parameters. Left ventricular myocytes from ß1ARKO mice showed increased (p < 0.05) amplitude and velocities of contraction and relaxation than those from WT. In addition, MCAE increased (p < 0.05) amplitude and velocities of contraction and relaxation in ß1ARKO mice. CONCLUSION: MCAE improves myocyte contractility in the left ventricle of ß1ARKO mice. This is evidence to support the therapeutic value of this type of exercise training in the treatment of heart diseases involving ß1-AR desensitization or reduction.


Assuntos
Contração Miocárdica/fisiologia , Miócitos Cardíacos/fisiologia , Condicionamento Físico Animal/métodos , Condicionamento Físico Animal/fisiologia , Receptores Adrenérgicos beta 1/fisiologia , Função Ventricular Esquerda/fisiologia , Animais , Teste de Esforço/métodos , Terapia por Exercício/métodos , Insuficiência Cardíaca/fisiopatologia , Masculino , Camundongos , Camundongos Knockout , Reprodutibilidade dos Testes , Fatores de Tempo
6.
J Cell Mol Med ; 22(3): 1452-1463, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29265674

RESUMO

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.


Assuntos
Atividade Motora/fisiologia , Atrofia Muscular/prevenção & controle , Condicionamento Físico Animal , Biossíntese de Proteínas , Insuficiência Renal Crônica/terapia , Fator 4 Ativador da Transcrição/genética , Fator 4 Ativador da Transcrição/metabolismo , Fator 6 Ativador da Transcrição/genética , Fator 6 Ativador da Transcrição/metabolismo , Animais , Catalase/genética , Catalase/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Testes de Função Renal , Masculino , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatologia , Atrofia Muscular/genética , Atrofia Muscular/metabolismo , Atrofia Muscular/fisiopatologia , Nefrectomia/métodos , Complexo de Endopeptidases do Proteassoma/metabolismo , Ratos , Ratos Wistar , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/cirurgia , Teste de Desempenho do Rota-Rod , Comportamento Sedentário , Transdução de Sinais
7.
Int J Sports Med ; 38(4): 270-277, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28219104

RESUMO

To evaluate whether captopril (3×50 mg/day) potentiates post-resistance exercise hypotension (PREH) in hypertensives (HT), 12 HT men received captopril and placebo for 4 weeks each in a double-blinded, randomized-crossover design. On each therapy, subjects underwent 2 sessions: Control (C - rest) and Resistance Exercise (RE - 7 exercises, 3 sets to moderate fatigue, 50% of 1 RM -repetition maximum). Measurements were taken before and after 30-60 min (Post1) and 7 h (Post2), and ambulatory blood pressure (BP) was monitored for 24 h. There were no differences in PREH characteristics and mechanisms between the placebo and captopril periods. At Post1, systolic/diastolic BP decreased significantly and similarly after RE with both therapies (Placebo=-13±2/-9±1 mmHg vs. Captopril=-12±2/-10±1 mmHg, P<0.05). RE reduced cardiac output in some subjects and systemic vascular resistance in others. Heart rate and cardiac sympathetic modulation increased, while stroke volume and baroreflex sensitivity decreased after RE (Placebo: +13±2 bpm, +21±5 nu, -11±5 ml, -4±2 ms/mmHg; Captopril: +13±2 bpm, +35±4 nu, 17±5 ml, -3±1 ms/mmHg, P<0.05). At Post2, all variables returned to pre-intervention values. Ambulatory BP was similar between the sessions. Thus, captopril did not potentiate the magnitude and duration of PREH in HT men, and it did not influence PREH mechanisms.


Assuntos
Captopril/administração & dosagem , Hipertensão/fisiopatologia , Hipotensão Pós-Exercício/tratamento farmacológico , Treinamento de Resistência , Anti-Hipertensivos/administração & dosagem , Pressão Sanguínea , Estudos Cross-Over , Método Duplo-Cego , Frequência Cardíaca , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Volume Sistólico , Resistência Vascular
8.
Mol Cell Biochem ; 424(1-2): 87-98, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27761848

RESUMO

Dexamethasone is a potent and widely used anti-inflammatory and immunosuppressive drug. However, recent evidences suggest that dexamethasone cause pathologic cardiac remodeling, which later impairs cardiac function. The mechanism behind the cardiotoxic effect of dexamethasone is elusive. The present study aimed to verify if dexamethasone-induced cardiotoxicity would be associated with changes in the cardiac net balance of calcium handling protein and calcineurin signaling pathway activation. Wistar rats (~400 g) were treated with dexamethasone (35 µg/g) in drinking water for 15 days. After dexamethasone treatment, we analyzed cardiac function, cardiomyocyte diameter, cardiac fibrosis, and the expression of proteins involved in calcium handling and calcineurin signaling pathway. Dexamethasone-treated rats showed several cardiovascular abnormalities, including elevated blood pressure, diastolic dysfunction, cardiac fibrosis, and cardiomyocyte apoptosis. Regarding the expression of proteins involved in calcium handling, dexamethasone increased phosphorylation of phospholamban at threonine 17, reduced protein levels of Na+/Ca2+ exchanger, and had no effect on protein expression of Serca2a. Protein levels of NFAT and GATA-4 were increased in both cytoplasmic and nuclear faction. In addition, dexamethasone increased nuclear protein levels of calcineurin. Altogether our findings suggest that dexamethasone causes pathologic cardiac remodeling and diastolic dysfunction, which is associated with impaired calcium handling and calcineurin signaling pathway activation.


Assuntos
Calcineurina/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Cardiomegalia/metabolismo , Dexametasona/efeitos adversos , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Cardiomegalia/induzido quimicamente , Cardiomegalia/patologia , Dexametasona/farmacologia , Masculino , Miocárdio/patologia , Miócitos Cardíacos/patologia , Ratos , Ratos Wistar
9.
Lasers Med Sci ; 32(2): 317-325, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27909917

RESUMO

We evaluated whether strength training (ST) performed prior to skeletal muscle cryolesion would act as a preconditioning, improving skeletal muscle regeneration and responsiveness to low-level laser therapy (LLLT). Wistar rats were randomly assigned into non-exercised (NE), NE plus muscle lesion (NE + LE), NE + LE plus LLLT (NE + LE + LLLT), strength training (ST), ST + LE, and ST + LE + LLLT. The animals performed 10 weeks of ST (climbing ladder; 3× week; 80% overload). Forty-eight hours after the last ST session, tibialis anterior (TA) cryolesion was induced and LLLT (InGaAlP, 660 nm, 0.035 W, 4.9 J/cm2/point, 3 points, spot light 0.028 cm2, 14 J/cm2) initiated and conducted daily for 14 consecutive days. The difference between intergroups was assessed using Student's t test and intragroups by two-way analysis of variance. Cryolesion induced massive muscle degeneration associated with inflammatory infiltrate. Prior ST improved skeletal regeneration 14-days after cryolesion and potentiated the regenerative response to LLLT. Cryolesion induced increased TNF-α levels in both NE + LE and ST + LE groups. Both isolated ST and LLLT reduced TNF-α to control group levels; however, prior ST potentiated LLLT response. Both isolated ST and LLLT increased IL-10 levels with no additional effect. In contrast, increased TA IL-6 levels were restricted to ST and ST + LE + LLLT groups. TA myogenin mRNA levels were not changed by neither prior ST or ST + LLLT. Both prior ST and LLLT therapies increased MyoD mRNA levels and, interestingly, combined therapies potentiated this response. Myf5 mRNA levels were increased only in ST groups. Taken together, our data provides evidences for prior ST potentiating LLLT efficacy in promoting skeletal muscle regeneration.


Assuntos
Terapia com Luz de Baixa Intensidade , Músculo Esquelético/lesões , Músculo Esquelético/efeitos da radiação , Condicionamento Físico Animal , Regeneração/efeitos da radiação , Animais , Citocinas/genética , Citocinas/metabolismo , Masculino , Modelos Biológicos , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Wistar , Cicatrização/efeitos da radiação
10.
Motriz (Online) ; 23(spe): e101625, 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-841860

RESUMO

Abstract The validity and relevance of research with animals for the development of knowledge in Exercise Science have for long been discussed. Given the complexity of the biological systems, the use of animal models offers a significant contribution to uncover new findings about acute and chronic effects of exercise, particularly when these studies in humans have limitations and ethical implications. There have been notable findings using experimental animals either in basic sciences or in clinical studies involving physiology, pharmacology, genetic, biochemistry, urology, endocrinology and cancer. This article presents a brief review of scientific research using animal models with a focus on exercise training as an effective tool for the prophylaxis and treatment of different pathological processes, which are the basis of many concepts taught and used in undergraduate courses and graduate programs, as well as in new researches showed in scientific conference meetings in numerous areas of science.(AU)


Assuntos
Humanos , Animais , Exercício , Modelos Animais , Educação Física e Treinamento
11.
Life Sci ; 163: 11-22, 2016 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-27575705

RESUMO

AIMS: Resistance exercise training (RET) has been adopted as non-pharmacological anti-catabolic strategy. However, the role of RET to counteract cancer cachexia is still speculative. This study aimed to verify whether short-term RET would counteract skeletal muscle wasting in a severe cancer cachexia rat model. MAIN METHODS: Wistar rats were randomly allocated into four experimental groups; 1) untrained control rats (control), 2) rats submitted to RET (control+RET), 3) untrained rats injected with Walker 256 tumor cells in the bone marrow (tumor) and 4) rats injected with Walker 256 tumor cells in the bone marrow and submitted to RET (tumor+RET). KEY FINDINGS: Tumor group displayed skeletal muscle atrophy fifteen days post tumor cells injection as assessed by plantaris (-20.5%) and EDL (-20.0%) muscle mass. EDL atrophy was confirmed showing 43.8% decline in the fiber cross sectional area. Even though RET increased the lactate dehydrogenase protein content and fully restored phosphorylated form of 4EBP-1 to the control levels in skeletal muscle, it failed to rescue muscle morphology in tumor-bearing rats. Indeed, RET did not mitigated loss of muscle function, anorexia, tumor growth or mortality rate. However, loss of strength capacity (assessed by 1-RM test performance) demonstrated a negative correlation with rats' survival (p=0.02; r=0.40), suggesting that loss of strength capacity might predict cancer mortality. SIGNIFICANCE: These results demonstrated that bone marrow injection of Walker 256 tumor cells in rats induces cancer cachexia, strength capacity is associated with cancer survival and short-term RET promotes only modest effects during cachexia progression.


Assuntos
Caquexia/complicações , Caquexia/terapia , Progressão da Doença , Atrofia Muscular/complicações , Atrofia Muscular/terapia , Treinamento de Resistência , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Anorexia/terapia , Linhagem Celular Tumoral , L-Lactato Desidrogenase/metabolismo , Masculino , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Neoplasias/complicações , Neoplasias/terapia , Ratos , Ratos Wistar , Taxa de Sobrevida
12.
Med Sci Sports Exerc ; 48(9): 1699-707, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27128665

RESUMO

INTRODUCTION: Exercise performed with blood flow restriction simultaneously enhances the acute responses to both myogenic and mitochondrial pathways with roles in training adaptation. We investigated isoform-specific gene expression of the peroxisome proliferator-activated receptor gamma coactivator 1 and selected target genes and proteins regulating skeletal muscle training adaptation. METHODS: Nine healthy, untrained males participated in a randomized, counterbalanced, crossover design in which each subject completed a bout of low-intensity endurance exercise performed with blood flow restriction (15 min cycling at 40% of V˙O2peak, BFR-EE), endurance exercise (30 min cycling at 70% of V˙O2peak, EE), or resistance exercise (4 × 10 repetitions of leg press at 70% of one-repetition maximum) separated by at least 1 wk of recovery. A single resting muscle biopsy (vastus lateralis) was obtained 2 wk before the first exercise trial (rest) and 3 h after each bout. RESULTS: Total PGC-1α mRNA abundance, along with all four isoforms, increased above rest with EE only (P < 0.05) being higher than BFR-EE (P < 0.05). PGC-1α1, 2, and 4 were higher after EE compared with resistance exercise (P < 0.05). EE also increased vascular endothelial growth factor, Hif-1α, and MuRF-1 mRNA abundance above rest (P < 0.05), whereas COXIV mRNA expression increased with EE compared with BFR-EE (P < 0.05). CONCLUSION: The attenuated expression of all four PGC-1α isoforms when EE is performed with blood flow restriction suggests this type of exercise provides an insufficient stimulus to activate the signaling pathways governing mitochondrial and angiogenesis responses observed with moderate- to high-intensity EE.


Assuntos
Exercício/fisiologia , Músculo Esquelético/fisiologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Adulto , Estudos Cross-Over , Teste de Esforço , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , Proteínas Musculares/metabolismo , Músculo Esquelético/irrigação sanguínea , Consumo de Oxigênio , Resistência Física , Isoformas de Proteínas/metabolismo , Fluxo Sanguíneo Regional , Treinamento de Resistência , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto Jovem
13.
PLoS One ; 11(1): e0146795, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26815679

RESUMO

A series of studies have demonstrated that activation of the sympathetic nervous system (SNS) causes osteopenia via ß2-adrenoceptor (ß2-AR) signaling. However, in a recent study, we found an unexpected and generalized phenotype of high bone mass in female mice with chronic sympathetic hyperactivity, due to double gene inactivation of adrenoceptors that negatively regulate norepinephrine release, α2A-and α2C-AR (α2A/2C-AR-/-). These findings suggest that ß2-AR is not the single adrenoceptor involved in bone turnover regulation and show that α2-AR signaling may also mediate the SNS actions in the skeleton. In addition, we found that α2A/2C-AR-/- animals are resistant to the thyrotoxicosis-induced osteopenia, suggesting that thyroid hormone (TH), when in supraphysiological levels, interacts with the SNS to control bone mass and structure, and that this interaction may also involve α2-AR signaling. In the present study, to further investigate these hypotheses and to discriminate the roles of α2-AR subtypes, we have evaluated the bone phenotype of mice with the single gene inactivation of α2C-AR subtype, which mRNA expression was previously shown to be down regulated by triiodothyronine (T3). A cohort of 30 day-old female α2CAR-/- mice and their wild-type (WT) controls were treated with a supraphysiological dose of T3 for 30 or 90 days, which induced a thyrotoxic state in both mouse lineages. The micro-computed tomographic (µCT) analysis showed that α2C-AR-/- mice present lower trabecular bone volume (BV/TV) and number (Tb.N), and increased trabecular separation (Tb.Sp) in the femur compared with WT mice; which was accompanied by decreased bone strength (determined by the three-point bending test) in the femur and tibia. The opposite was observed in the vertebra, where α2C-AR-/- mice show increased BV/TV, Tb.N and trabecular thickness (Tb.Th), and decreased Tb.Sp, compared with WT animals. In spite of the contrasting bone phenotypes of the femur and L5, thyrotoxicosis negatively regulated most of the micro architectural features of the trabecular bone in both skeletal sites of WT, but not of α2C-AR-/- mice. T3 treatment also decreased biomechanical properties (maximum load and ultimate load) in the femur and tibia of WT, but not of knockout mice. The mRNA expression of osteocalcin, a marker of mature osteoblasts, and tartrate-resistant acid phosphatase, which is expressed by osteoclasts and is involved in collagen degradation, was increased by T3 treatment only in WT, and not in α2C-AR-/- mice. Altogether, these findings suggest that α2C-AR subtype mediates the effects of the SNS in the bone in a skeletal site-dependent manner, and that thyrotoxicosis depends on α2C-AR signaling to promote bone loss, which sustains the hypothesis of a TH-SNS interaction to modulate bone remodeling and structure.


Assuntos
Doenças Ósseas Metabólicas/etiologia , Receptores Adrenérgicos alfa 2/genética , Tireotoxicose/complicações , Animais , Fenômenos Biomecânicos , Doenças Ósseas Metabólicas/sangue , Remodelação Óssea , Feminino , Fêmur/metabolismo , Fêmur/fisiopatologia , Expressão Gênica , Camundongos Knockout , Fenótipo , Receptores Adrenérgicos alfa 2/metabolismo , Transdução de Sinais , Coluna Vertebral/metabolismo , Coluna Vertebral/fisiopatologia , Tireotoxicose/sangue , Tireotoxicose/genética , Tiroxina/sangue , Tíbia/metabolismo , Tíbia/fisiopatologia , Tri-Iodotironina/sangue
14.
PLoS One ; 10(5): e0127843, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25996919

RESUMO

BACKGROUND: Besides its role as a fuel source in intermediary metabolism, lactate has been considered a signaling molecule modulating lactate-sensitive genes involved in the regulation of skeletal muscle metabolism. Even though the flux of lactate is significantly high in the heart, its role on regulation of cardiac genes regulating lactate oxidation has not been clarified yet. We tested the hypothesis that lactate would increase cardiac levels of reactive oxygen species and up-regulate the expression of genes related to lactate oxidation complex. METHODS/PRINCIPAL FINDINGS: Isolated hearts from male adult Wistar rats were perfused with control, lactate or acetate (20mM) added Krebs-Henseleit solution during 120 min in modified Langendorff apparatus. Reactive oxygen species (O2●-/H2O2) levels, and NADH and NADPH oxidase activities (in enriched microsomal or plasmatic membranes, respectively) were evaluated by fluorimetry while SOD and catalase activities were evaluated by spectrophotometry. mRNA levels of lactate oxidation complex and energetic enzymes MCT1, MCT4, HK, LDH, PDH, CS, PGC1α and COXIV were quantified by real time RT-PCR. Mitochondrial DNA levels were also evaluated. Hemodynamic parameters were acquired during the experiment. The key findings of this work were that lactate elevated cardiac NADH oxidase activity but not NADPH activity. This response was associated with increased cardiac O2●-/H2O2 levels and up-regulation of MCT1, MCT4, LDH and PGC1α with no changes in HK, PDH, CS, COXIV mRNA levels and mitochondrial DNA levels. Lactate increased NRF-2 nuclear expression and SOD activity probably as counter-regulatory responses to increased O2●-/H2O2. CONCLUSIONS: Our results provide evidence for lactate-induced up-regulation of lactate oxidation complex associated with increased NADH oxidase activity and cardiac O2●-/H2O2 driving to an anti-oxidant response. These results unveil lactate as an important signaling molecule regulating components of the lactate oxidation complex in cardiac muscle.


Assuntos
Regulação da Expressão Gênica , Ventrículos do Coração/metabolismo , Ácido Láctico/metabolismo , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Metabolismo Energético , Hemodinâmica , Peróxido de Hidrogênio/metabolismo , Técnicas In Vitro , Masculino , Miocárdio/metabolismo , NAD/metabolismo , NADPH Oxidases/metabolismo , Oxirredução , Ratos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Superóxido Dismutase/metabolismo , Regulação para Cima , Função Ventricular
15.
Nutrients ; 7(5): 3751-66, 2015 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-25988767

RESUMO

Leucine supplementation potentiates the effects of aerobic exercise training (AET) on skeletal muscle; however, its potential effects associated with AET on cardiac muscle have not been clarified yet. We tested whether leucine supplementation would potentiate the anti-cardiac remodeling effect of AET in a genetic model of sympathetic hyperactivity-induced heart failure in mice (α2A/α2CARKO). Mice were assigned to five groups: wild type mice treated with placebo and sedentary (WT, n = 11), α2A/α2CARKO treated with placebo and sedentary (KO, n = 9), α2A/α2CARKO treated with leucine and sedentary (KOL, n = 11), α2A/α2CARKO treated with placebo and AET (KOT, n = 12) or α2A/α2CARKO treated with leucine and AET (KOLT, n = 12). AET consisted of four weeks on a treadmill with 60 min sessions (six days/week, 60% of maximal speed) and administration by gavage of leucine (1.35 g/kg/day) or placebo (distilled water). The AET significantly improved exercise capacity, fractional shortening and re-established cardiomyocytes' diameter and collagen fraction in KOT. Additionally, AET significantly prevented the proteasome hyperactivity, increased misfolded proteins and HSP27 expression. Isolated leucine supplementation displayed no effect on cardiac function and structure (KOL), however, when associated with AET (KOLT), it increased exercise tolerance to a higher degree than isolated AET (KOT) despite no additional effects on AET induced anti-cardiac remodeling. Our results provide evidence for the modest impact of leucine supplementation on cardiac structure and function in exercised heart failure mice. Leucine supplementation potentiated AET effects on exercise tolerance, which might be related to its recognized impact on skeletal muscle.


Assuntos
Suplementos Nutricionais , Tolerância ao Exercício/efeitos dos fármacos , Insuficiência Cardíaca/patologia , Coração/efeitos dos fármacos , Leucina/farmacologia , Miocárdio/patologia , Condicionamento Físico Animal/fisiologia , Animais , Colágeno/metabolismo , Teste de Esforço , Proteínas de Choque Térmico HSP27/metabolismo , Coração/fisiopatologia , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Leucina/uso terapêutico , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Esquelético/efeitos dos fármacos , Miocárdio/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Dobramento de Proteína/efeitos dos fármacos , Sistema Nervoso Simpático
16.
Oxid Med Cell Longev ; 2015: 464195, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25954323

RESUMO

BACKGROUND: We previously reported that exercise training (ET) facilitates the clearance of damaged proteins in heart failure. Here, we characterized the impact of ET on cardiac protein quality control during compensated ventricular hypertrophy in spontaneously hypertensive rats (SHR). METHODS AND RESULTS: SHR were randomly assigned into sedentary and swimming-trained groups. Sedentary SHR displayed cardiac hypertrophy with preserved ventricular function compared to normotensive rats, characterizing a compensated cardiac hypertrophy. Hypertensive rats presented signs of cardiac oxidative stress, depicted by increased lipid peroxidation. However, these changes were not followed by accumulation of lipid peroxidation-generated reactive aldehydes and damaged proteins. This scenario was explained, at least in part, by the increased catalytic activity of both aldehyde dehydrogenase 2 (ALDH2) and proteasome. Of interest, ET exacerbated cardiac hypertrophy, improved ventricular function, induced resting bradycardia, and decreased blood pressure in SHR. These changes were accompanied by reduced cardiac oxidative stress and a consequent decrease in ALDH2 and proteasome activities, without affecting small chaperones levels and apoptosis in SHR. CONCLUSION: Increased cardiac ALDH2 and proteasomal activities counteract the deleterious effect of excessive oxidative stress in hypertension-induced compensated cardiac hypertrophy in rats. ET has a positive effect in reducing cardiac oxidative stress without affecting protein quality control.


Assuntos
Aldeídos/metabolismo , Cardiomegalia/etiologia , Hipertensão/complicações , Aldeído Desidrogenase/metabolismo , Aldeído-Desidrogenase Mitocondrial , Animais , Pressão Sanguínea , Cardiomegalia/metabolismo , Frequência Cardíaca , Peroxidação de Lipídeos , Masculino , Proteínas Mitocondriais/metabolismo , Condicionamento Físico Animal , Complexo de Endopeptidases do Proteassoma/metabolismo , Carbonilação Proteica , Ratos , Ratos Endogâmicos SHR
17.
Mol Cell Biochem ; 402(1-2): 193-202, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25626892

RESUMO

The activity of the ubiquitin proteasome system (UPS) and the level of oxidative stress contribute to the transition from compensated cardiac hypertrophy to heart failure in hypertension. Moreover, aerobic exercise training (AET) is an important therapy for the treatment of hypertension, but its effects on the UPS are not completely known. The aim of this study was to evaluate the effect of AET on UPS's activity and oxidative stress level in heart of spontaneously hypertensive rats (SHR). A total of 53 Wistar and SHR rats were randomly divided into sedentary and trained groups. The AET protocol was 5×/week in treadmill for 13 weeks. Exercise tolerance test, non-invasive blood pressure measurement, echocardiographic analyses, and left ventricle hemodynamics were performed during experimental period. The expression of ubiquitinated proteins, 4-hydroxynonenal (4-HNE), Akt, phospho-Akt(ser473), GSK3ß, and phospho-GSK3ß(ser9) were analyzed by western blotting. The evaluation of lipid hydroperoxide concentration was performed using the xylenol orange method, and the proteasomal chymotrypsin-like activity was measured by fluorimetric assay. Sedentary hypertensive group presented cardiac hypertrophy, unaltered expression of total Akt, phospho-Akt, total GSK3ß and phospho-GSK3ß, UPS hyperactivity, increased lipid hydroperoxidation as well as elevated expression of 4-HNE but normal cardiac function. In contrast, AET significantly increased exercise tolerance, decreased resting systolic blood pressure and heart rate in hypertensive animals. In addition, the AET increased phospho-Akt expression, decreased phospho-GSK3ß, and did not alter the expression of total Akt, total GSK3ß, and ubiquitinated proteins, however, significantly attenuated 4-HNE levels, lipid hydroperoxidation, and UPS's activity toward normotensive group levels. Our results provide evidence for the main effect of AET on attenuating cardiac ubiquitin proteasome hyperactivity and oxidative stress in SHR rats.


Assuntos
Hipertensão/terapia , Miocárdio/metabolismo , Estresse Oxidativo , Complexo de Endopeptidases do Proteassoma/fisiologia , Animais , Tamanho Celular , Terapia por Exercício , Hipertensão/metabolismo , Masculino , Miócitos Cardíacos/patologia , Condicionamento Físico Animal , Proteólise , Ratos Endogâmicos SHR , Ratos Wistar , Transdução de Sinais , Ubiquitina/metabolismo , Ubiquitinação , Resposta a Proteínas não Dobradas
18.
Life Sci ; 125: 9-14, 2015 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-25500304

RESUMO

Aerobic exercise training (AET) induces several skeletal muscle changes, improving aerobic exercise capacity and health. Conversely, to the positive effects of AET, the cachexia syndrome is characterized by skeletal muscle wasting. Cachexia is a multifactorial disorderassociated with other chronic diseases such as heart failure and cancer. In these diseases, an overactivation of ubiquitin-proteasome and autophagy systems associated with a reduction in protein synthesis culminates in severe skeletal muscle wasting and, in the last instance, patient's death. In contrast, AET may recycle and enhance many protein expression and enzyme activities, counteracting metabolism impairment and muscle atrophy. Therefore, the aim of the current review was to discuss the supposed therapeutic effects of AET on skeletal muscle wasting in both cardiac and cancer cachexia.


Assuntos
Caquexia/complicações , Caquexia/terapia , Terapia por Exercício , Insuficiência Cardíaca/complicações , Doenças Musculares/complicações , Doenças Musculares/terapia , Neoplasias/complicações , Animais , Caquexia/metabolismo , Exercício , Terapia por Exercício/métodos , Insuficiência Cardíaca/metabolismo , Humanos , Atrofia Muscular/complicações , Atrofia Muscular/metabolismo , Atrofia Muscular/terapia , Doenças Musculares/metabolismo , Neoplasias/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo
19.
PLoS One ; 9(10): e108543, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25272046

RESUMO

Nephrotoxicity is substantial side effect for 30% of patients undergoing cancer therapy with cisplatin and may force them to change or even abandon the treatment. Studies regarding aerobic exercise have shown its efficacy for the treatment of many types of diseases and its capacity to reduce tumors. However, little is known about the impact of physical exercise on cisplatin-induced acute kidney injury (AKI). In the present study, our aim was to investigate the role of physical exercise in AKI induced by cisplatin. We submitted C57Bl6 male mice to seven weeks of chronic exercise on a training treadmill and treated them with single i.p. injection of cisplatin (20 mg/kg) in the last week. Exercise efficacy was confirmed by an increased capillary-to-fiber ratio in the gastrocnemius muscle of exercised groups (EX and CIS-EX). The group submitted to exercise before cisplatin administration (CIS-EX) exhibited less weight loss and decreased serum urea levels compared to the cisplatin group (CIS). Exercise also showed a protective role against cisplatin-induced cell death in the kidney. The CIS-EX group showed a lower inflammatory response, with less TNF and IL-10 expression in the kidney and serum. In the same group, we observed an increase of IL-6 and HO-1 expression in the kidney. Taken together, our results indicate that chronic aerobic exercise is able to attenuate AKI by inducing IL-6 and HO-1 production, which results in lower inflammatory and apoptotic profiles in the kidney.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/genética , Cisplatino/efeitos adversos , Regulação da Expressão Gênica , Interleucina-6/genética , Condicionamento Físico Animal , Lesão Renal Aguda/patologia , Lesão Renal Aguda/fisiopatologia , Lesão Renal Aguda/prevenção & controle , Animais , Apoptose/efeitos dos fármacos , Caquexia/etiologia , Caquexia/prevenção & controle , Cisplatino/administração & dosagem , Cisplatino/farmacologia , Modelos Animais de Doenças , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Inflamação/genética , Inflamação/metabolismo , Interleucina-6/metabolismo , Masculino , Camundongos , Fatores de Necrose Tumoral/genética , Fatores de Necrose Tumoral/metabolismo
20.
PLoS One ; 9(5): e98012, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24859374

RESUMO

BACKGROUND: Accumulated evidence shows that the ACE-AngII-AT1 axis of the renin-angiotensin system (RAS) is markedly activated in chronic heart failure (CHF). Recent studies provide information that Angiotensin (Ang)-(1-7), a metabolite of AngII, counteracts the effects of AngII. However, this balance between AngII and Ang-(1-7) is still little understood in CHF. We investigated the effects of exercise training on circulating and skeletal muscle RAS in the ischemic model of CHF. METHODS/MAIN RESULTS: Male Wistar rats underwent left coronary artery ligation or a Sham operation. They were divided into four groups: 1) Sedentary Sham (Sham-S), 2) exercise-trained Sham (Sham-Ex), sedentary CHF (CHF-S), and exercise-trained CHF (CHF-Ex). Angiotensin concentrations and ACE and ACE2 activity in the circulation and skeletal muscle (soleus and plantaris) were quantified. Skeletal muscle ACE and ACE2 protein expression, and AT1, AT2, and Mas receptor gene expression were also evaluated. CHF reduced ACE2 serum activity. Exercise training restored ACE2 and reduced ACE activity in CHF. Exercise training reduced plasma AngII concentration in both Sham and CHF rats and increased the Ang-(1-7)/AngII ratio in CHF rats. CHF and exercise training did not change skeletal muscle ACE and ACE2 activity and protein expression. CHF increased AngII levels in both soleus and plantaris muscle, and exercise training normalized them. Exercise training increased Ang-(1-7) in the plantaris muscle of CHF rats. The AT1 receptor was only increased in the soleus muscle of CHF rats, and exercise training normalized it. Exercise training increased the expression of the Mas receptor in the soleus muscle of both exercise-trained groups, and normalized it in plantaris muscle. CONCLUSIONS: Exercise training causes a shift in RAS towards the Ang-(1-7)-Mas axis in skeletal muscle, which can be influenced by skeletal muscle metabolic characteristics. The changes in RAS circulation do not necessarily reflect the changes occurring in the RAS of skeletal muscle.


Assuntos
Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/metabolismo , Músculo Esquelético/metabolismo , Condicionamento Físico Animal , Sistema Renina-Angiotensina , Angiotensina II/sangue , Angiotensina II/metabolismo , Animais , Insuficiência Cardíaca/fisiopatologia , Testes de Função Cardíaca , Masculino , Peptidil Dipeptidase A/sangue , Peptidil Dipeptidase A/metabolismo , Ratos , Ratos Wistar
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