Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.106
Filtrar
1.
Braz J Med Biol Res ; 52(12): e8576, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31800730

RESUMO

Physical exercise is a known preventive and therapeutic alternative for several cerebrovascular diseases. Therefore, the objective of the present study was to evaluate the motor performance and histomorphometry of the biceps brachii, soleus, and tibialis anterior muscles of rats submitted to a treadmill training program prior to the induction of cerebral ischemia via occlusion of the middle cerebral artery (OMCA). A total of 24 Wistar rats were distributed into four groups: Sham-Sed: sedentary control animals (n=6), who underwent sham surgery (in which OMCA did not occur); Sham+Ex: control animals exercised before the sham surgery (n=6); I-Sed: sedentary animals with cerebral ischemia (n=6); and I+Ex: animals exercised before the induction of ischemia (n=6). The physical exercise consisted of treadmill training for five weeks, 30 min/day (5 days/week), at a speed of 14 m/min. The results showed that the type-I fibers presented greater fiber area in the exercised ischemic group (I+Ex: 2347.96±202.77 µm2) compared to the other groups (Sham-Sed: 1676.46±132.21 µm2; Sham+Ex: 1647.63±191.09 µm2; I+Ex: 1566.93±185.09 µm2; P=0.0002). Our findings suggested that the angiogenesis process may have influenced muscle recovery and reduced muscle atrophy of type-I fibers in the animals that exercised before cerebral ischemia.


Assuntos
Isquemia Encefálica/complicações , Infarto da Artéria Cerebral Média , Músculo Esquelético/fisiopatologia , Atrofia Muscular/prevenção & controle , Condicionamento Físico Animal/fisiologia , Animais , Isquemia Encefálica/fisiopatologia , Modelos Animais de Doenças , Masculino , Atrofia Muscular/etiologia , Atrofia Muscular/patologia , Ratos , Ratos Wistar
2.
Life Sci ; 237: 116919, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31610200

RESUMO

AIMS: Stroke-prone spontaneously hypertensive rats (SHRSP) show significantly lower body weight than normotensive Wistar-Kyoto rats (WKY). Our hypotheses are as follows: weight loss of the skeletal muscle is related to hypertension-related diseases, and muscle hypotrophy is useful as a therapeutic target for hypertension and hypertension-related diseases. In this study, we aimed to investigate the pathophysiological characteristics of muscle hypotrophy in SHRSP to determine the therapeutic target molecule(s). MAIN METHODS: The difference in skeletal muscles in the lower leg between WKY and SHRSP was evaluated mainly through weight/tibial length, histological, gene expression, and protein expression analyses. KEY FINDINGS: SHRSP had a significantly lower weight/tibial length in soleus and gastrocnemius, but not in plantaris and tibialis anterior, indicating that muscles consisting of a relatively high amount of slow muscle fiber were affected. This result was confirmed by the histological analysis of soleus, showing that type I fiber mainly decreased the fiber size. Microarray and protein expression analyses showed that the muscle-specific ubiquitin ligase, muscle RING finger 1 (MuRF1), but not atrogin-1, was highly expressed in soleus, but not in plantaris, in SHRSP. TNF-like weak inducer of apoptosis receptor (TWEAKR) was predicted as a MuRF1 up-regulator by Ingenuity Pathway Analysis and immunostained only in type II fiber in WKY but in both type I and II fibers in SHRSP. SIGNIFICANCE: TWEAKR is a type II-specific receptor in the skeletal muscle. Ectopic TWEAKR expression in type I fiber of SHRSP is most likely involved in slow muscle-specific hypotrophy through MuRF1 overexpression.


Assuntos
Hipertensão/patologia , Fibras Musculares Esqueléticas/patologia , Músculo Esquelético/patologia , Músculo Liso Vascular/patologia , Atrofia Muscular/patologia , Acidente Vascular Cerebral/patologia , Receptor de TWEAK/metabolismo , Animais , Hipertensão/complicações , Hipertensão/metabolismo , Masculino , Fibras Musculares Esqueléticas/metabolismo , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Músculo Liso Vascular/metabolismo , Atrofia Muscular/etiologia , Atrofia Muscular/metabolismo , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/metabolismo , Receptor de TWEAK/genética , Proteínas com Motivo Tripartido/genética , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
3.
Life Sci ; 235: 116800, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31472151

RESUMO

AIMS: It is well known that cigarette smoke (CS) is the main risk factor for chronic obstructive pulmonary disease (COPD) accompanied by skeletal muscle atrophy. Histone deacetylases (HDACs) that remove acetyl groups from target proteins are necessary for the muscle atrophy associated with skeletal muscle disuse. However, the role of HDACs and trichostatin A (TSA), a HDAC inhibitor, in skeletal muscle atrophy caused by CS exposure remains poorly understood. MAIN METHODS: Female mice were exposed to CS twice daily for 40 days and TSA injected intraperitoneally into CS-exposed mice on alternate days. Skeletal muscles were weighed and gastrocnemius (Gas) muscle histomorphology examined by hematoxylin and eosin staining. Histone deacetylases 1 and 2 (HDAC1/2), and markers of ubiquitin degradation, muscle differentiation, apoptosis, pyroptosis, and the cytoskeletal proteins were assessed by western blot and immunohistochemistry in Gas. KEYFINDINGS: CS exposure decreased body and skeletal muscle weights and triggered an increase in the percentage of fiber with centralized nuclei in Gas. HDAC1/2 proteins were upregulated in the Gas of mice exposed to CS, while TSA effectively inhibited HDAC1/2 protein levels and attenuated the loss of body weight and skeletal muscle wet weight induced by CS exposure. Markers for ubiquitin degradation, muscle differentiation, cytoskeletal proteins, apoptosis and pyroptosis were all upregulated following CS exposure and effectively restored by TSA. SIGNIFICANCE: TSA may inhibit skeletal muscle atrophy and histomorphological alterations induced by CS exposure by downregulating markers of ubiquitin degradation, muscle fiber differentiation, cytoskeletal proteins, apoptosis and pyroptosis via HDAC1/2 inhibition.


Assuntos
Apoptose/efeitos dos fármacos , Histona Desacetilase 1/antagonistas & inibidores , Inibidores de Histona Desacetilases/farmacologia , Ácidos Hidroxâmicos/farmacologia , Músculo Esquelético/efeitos dos fármacos , Atrofia Muscular/tratamento farmacológico , Fumar/efeitos adversos , Animais , Proteínas do Citoesqueleto/metabolismo , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Atrofia Muscular/etiologia , Atrofia Muscular/patologia
4.
Muscle Nerve ; 60(6): 739-744, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31449671

RESUMO

BACKGROUND: Hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) is characterized by adult onset, a slowly progressive course and autosomal dominant inheritance. It remains unclear whether myopathic changes occur histopathologically. METHODS: We encountered 2 patients in a family with a heterozygous p.P285L mutation in TRK-fused gene (TFG), which is known to cause HMSN-P. The affected individuals developed proximal-dominant muscle weakness in their 40s, which slowly progressed to a motor neuron disease-like phenotype. RESULTS: Muscle biopsy showed myopathic pathology including fiber size variability, increased internal nuclei, fiber splitting, and core-like structures, associated with neurogenic changes: large groups of atrophic fibers and fiber type-grouping. Immunohistochemistry revealed sarcoplasmic aggregates of TFG, TDP-43, and p62 without congophilic material. CONCLUSIONS: The present study demonstrates myopathic changes in HMSN-P. Although the mechanisms underlying the skeletal muscle involvement remain to be elucidated, immunohistochemistry suggests that abnormal protein aggregation may be involved in the myopathic pathology.


Assuntos
Neuropatia Hereditária Motora e Sensorial/patologia , Fibras Musculares Esqueléticas/patologia , Músculo Esquelético/patologia , Potenciais de Ação , Proteínas de Ligação a DNA/metabolismo , Feminino , Imunofluorescência , Neuropatia Hereditária Motora e Sensorial/diagnóstico por imagem , Neuropatia Hereditária Motora e Sensorial/genética , Neuropatia Hereditária Motora e Sensorial/fisiopatologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Atrofia Muscular/patologia , Condução Nervosa , Linhagem , Proteínas/genética , Proteínas de Ligação a RNA/metabolismo , Retículo Sarcoplasmático/metabolismo , Irmãos
5.
Biomed Res Int ; 2019: 3719643, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31467885

RESUMO

Background: The clinical anti-inflammatory drug dexamethasone (DEX) can cause many side effects such as muscle atrophy for long-term use. Muscle atrophy induced by DEX may be caused by decrease of glucose consumption. Panax ginseng C.A. Meyer was previously considered to be an antiatrophic agent for glucocorticoid- (GC-) treated therapies. As one of the main components, it remains unclear whether ginseng total protein (GP) facilitates recovery from muscle atrophy induced by DEX. Methods: In this study, GP was extracted and purified with Sephadex-G50. C2C12 myoblasts was induced with 2% horse serum to differentiate into C2C12 myotubes. Cell viability was analyzed by the MTT assay, and Ca2+ concentration was analyzed by a flow cytometer. The release of lactic dehydrogenase (LDH) and the glucose consumption were analyzed by spectrophotometry. The phosphorylation of AMP-activated protein kinase (AMPK), phosphoinositide 3-kinase (PI3K), and protein kinase B (Akt) and the expression of glucose transporter 4 (GLUT4) were analyzed by Western blotting. The phosphorylation of AS160 was quantified by Immunofluorescence staining. Results: We found that GP increased cell viability and increased myotube diameter in high-dose DEX-treated C2C12 myotubes for 24 h, but this activity was not found in the enzymatic hydrolyzed GP group. GP reduced muscle atrophy by decreasing the expression of key proteins such as muscle RING-finger protein-1 and muscle atrophy F-box, reducing the Ca2+ concentration, and decreasing the release of LDH in DEX-injured C2C12 myotubes. Moreover, GP improved glucose consumption and increased the phosphorylation of AMPK, PI3K, Akt, and AS160 and the expression of GLUT4 in DEX-treated C2C12 myotubes. Conclusion: The results of this study suggest that GP has effects on recovering DEX-induced muscle atrophy and cell injury, which may improve glucose consumption via the AMPK and PI3K/Akt pathways in high-dose DEX-treated C2C12 myotubes. This study provides in vitro mechanistic insights into the recovery of muscle atrophy with GP treatment.


Assuntos
Glucose/metabolismo , Atrofia Muscular/tratamento farmacológico , Panax/química , Extratos Vegetais/farmacologia , Animais , Dexametasona/toxicidade , Expressão Gênica/efeitos dos fármacos , Transportador de Glucose Tipo 4 , Humanos , Camundongos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/patologia , Mioblastos/efeitos dos fármacos , Mioblastos/patologia , Fosforilação/efeitos dos fármacos , Extratos Vegetais/química
6.
Biomed Pharmacother ; 117: 109197, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31387190

RESUMO

Sucrose nonfermenting AMPK-related kinase (SNARK) is a member of the AMPK family of kinases and has been implicated in the regulation of critical metabolic processes. Recent findings demonstrate that SNARK has an important role in the maintenance of muscle mass with age. Loss of skeletal muscle mass (cachexia) is a key problem for cancer patients. Thus, based on our previous findings with aging, we hypothesized that SNARK would play a role in regulating muscle mass under conditions of cancer cachexia. To test this hypothesis, Lewis Lung Carcinoma tumor cells or vehicle were injected subcutaneously in the right flank of wild type mice, muscle-specific transgenic mice expressing inactive SNARK mutant (SDN) or muscle-specific transgenic mice overexpressing wild-type SNARK (SWT). All tumor-bearing mice presented muscle wasting compared to vehicle-injected mice. However, SDN tumor-bearing mice had more pronounced atrophy compared to wild-type and SWT tumor-bearing mice. Histological analysis confirmed muscle atrophy in tumor-bearing mice, and SDN tumor-bearing mice exhibited a significantly smaller skeletal muscle cross-sectional area than wild-type and SWT tumor-bearing mice. Moreover, SDN tumor-bearing mice had increased skeletal muscle BAX protein expression, a marker of apoptosis, compared to other groups.Thus, lack of SNARK in skeletal muscle aggravates cancer-induced skeletal muscle wasting. These findings uncover a role for SNARK in the maintenance of skeletal muscle mass under cachexia conditions.


Assuntos
Carcinoma Pulmonar de Lewis/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Proteínas Serina-Treonina Quinases/metabolismo , Sacarose/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Apoptose/fisiologia , Caquexia/metabolismo , Caquexia/patologia , Carcinoma Pulmonar de Lewis/complicações , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Atrofia Muscular/etiologia
7.
Nutrients ; 11(8)2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31344809

RESUMO

Military personnel may be exposed to circumstances (e.g., large energy deficits, sleep deprivation, cognitive demands, and environmental extremes) of external stressors during training and combat operations (i.e., operational stressors) that combine to degrade muscle protein. The loss of muscle protein is further exacerbated by frequent periods of severe energy deficit. Exposure to these factors results in a hypogonadal state that may contribute to observed decrements in muscle mass. In this review, lessons learned from studying severe clinical stressed states and the interventions designed to mitigate the loss of muscle protein are discussed in the context of military operational stress. For example, restoration of the anabolic hormonal status (e.g., testosterone, insulin, and growth hormone) in stressed physiological states may be necessary to restore the anabolic influence derived from dietary protein on muscle. Based on our clinical experiences, restoration of the normal testosterone status during sustained periods of operational stress may be advantageous. We demonstrated that in severe burn patients, pharmacologic normalization of the anabolic hormonal status restores the anabolic stimulatory effect of nutrition on muscle by improving the protein synthetic efficiency and limiting amino acid loss from skeletal muscle. Furthermore, an optimal protein intake, and in particular essential amino acid delivery, may be an integral ingredient in a restored anabolic response during the stress state. Interventions which improve the muscle net protein balance may positively impact soldier performance in trying conditions.


Assuntos
Proteínas na Dieta/administração & dosagem , Medicina Militar , Militares , Contração Muscular , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Atrofia Muscular/prevenção & controle , Doenças Profissionais/prevenção & controle , Estresse Fisiológico , Animais , Proteínas na Dieta/metabolismo , Metabolismo Energético , Hormônios/metabolismo , Humanos , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Atrofia Muscular/fisiopatologia , Estado Nutricional , Doenças Profissionais/metabolismo , Doenças Profissionais/patologia , Doenças Profissionais/fisiopatologia , Saúde do Trabalhador , Fatores de Proteção , Fatores de Risco
8.
Nat Commun ; 10(1): 3187, 2019 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-31320633

RESUMO

Loss of innervation of skeletal muscle is a determinant event in several muscle diseases. Although several effectors have been identified, the pathways controlling the integrated muscle response to denervation remain largely unknown. Here, we demonstrate that PKB/Akt and mTORC1 play important roles in regulating muscle homeostasis and maintaining neuromuscular endplates after nerve injury. To allow dynamic changes in autophagy, mTORC1 activation must be tightly balanced following denervation. Acutely activating or inhibiting mTORC1 impairs autophagy regulation and alters homeostasis in denervated muscle. Importantly, PKB/Akt inhibition, conferred by sustained mTORC1 activation, abrogates denervation-induced synaptic remodeling and causes neuromuscular endplate degeneration. We establish that PKB/Akt activation promotes the nuclear import of HDAC4 and is thereby required for epigenetic changes and synaptic gene up-regulation upon denervation. Hence, our study unveils yet-unknown functions of PKB/Akt-mTORC1 signaling in the muscle response to nerve injury, with important implications for neuromuscular integrity in various pathological conditions.


Assuntos
Autofagia/fisiologia , Histona Desacetilases/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Denervação Muscular , Músculo Esquelético/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Linhagem Celular , Alvo Mecanístico do Complexo 1 de Rapamicina/antagonistas & inibidores , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Camundongos , Placa Motora/patologia , Atrofia Muscular/patologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/genética
9.
Arch Physiol Biochem ; 125(5): 470-477, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31291133

RESUMO

Context: Skeletal muscle atrophy is a complication of diabetes, partially induced by nicotinamide adenine dinucleotide (NAD+) deficiency. Objective: This study investigates the potential of nicotinamide (NAM) supplementation, a precursor of NAD+, against muscle atrophy. Methods: Mice were separated into normal control group, normal control with NAM administration group, diabetic group, and diabetic mice with NAM administration group. Basic characteristics, muscle weight, maximal grip strength, and myofibers cross-sectional area were analysed. Markers reflecting muscle atrophy and hypertrophy, and transforming growth factor ß1/Smad2 (TGF-ß1/Smad2) pathway were examined. Results: NAM did not influence body weight and blood glucose. In diabetic mice, NAM increased NAD+ level, rescued muscle weight and strength loss, and increased myofibers cross-sectional area. NAM inhibited MuRF1 and Atrogin1, while elevated phosphorylation of Akt. Overactivation of TGF-ß1/Smad2 pathway was repressed by NAM. Conclusion: NAM ameliorated diabetic muscle atrophy by rebalancing protein anabolism and catabolism, probably through de-activation of TGF-ß1/Smad2 signaling.


Assuntos
Diabetes Mellitus Experimental/complicações , Músculo Esquelético/efeitos dos fármacos , Atrofia Muscular/complicações , Atrofia Muscular/prevenção & controle , Niacinamida/farmacologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Proteólise/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Proteína Smad2/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
10.
Int J Sports Med ; 40(8): 544-550, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31288294

RESUMO

Circumference measurements have been used to estimate muscle cross-sectional area (CSA) in clinical settings. Measurements of thigh circumference are affected by muscle and subcutaneous fat (SF). In fact, SF could increase over a short period. Therefore, clarifying the relationship between thigh circumference and muscle and SF following ACL reconstruction is important. This study's primary purpose was to examine pre- and post-operative changes in thigh circumference, thigh muscles and SF CSAs in both legs. Secondary, the relationship between thigh circumference and muscle and SF CSAs was examined to demonstrate that circumference measurements could be used to detect atrophy. Quadriceps, hamstrings, and SF CSAs at 15, 10, and 5 cm proximal to the patella were measured by MRI pre- and 4 weeks postoperatively to examine how reconstruction affected those tissues in the thighs. The results showed increases in SF CSA (r=0.72 at 10 cm, r=0.67 at 15 cm) greatly affected thigh circumference in females on the surgical side. In males, increases in SF CSA (r=0.83) at 15- and 5-cm and decreases in quadriceps muscle CSA (r=0.73) at 5 cm affected thigh circumference on the surgical side. Thigh circumference measurements might not reflect actual muscle CSA in ACL patients.


Assuntos
Reconstrução do Ligamento Cruzado Anterior , Músculos Isquiotibiais/anatomia & histologia , Atrofia Muscular/patologia , Músculo Quadríceps/anatomia & histologia , Gordura Subcutânea/anatomia & histologia , Coxa da Perna/anatomia & histologia , Adolescente , Adulto , Feminino , Músculos Isquiotibiais/diagnóstico por imagem , Músculos Isquiotibiais/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Atrofia Muscular/diagnóstico por imagem , Período Pós-Operatório , Músculo Quadríceps/diagnóstico por imagem , Músculo Quadríceps/patologia , Gordura Subcutânea/diagnóstico por imagem , Gordura Subcutânea/patologia , Coxa da Perna/diagnóstico por imagem , Coxa da Perna/patologia , Adulto Jovem
11.
Biol Pharm Bull ; 42(7): 1128-1133, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31257289

RESUMO

In diabetic patients, skeletal muscle atrophy occurs due to increased oxidative stress and inflammation. Skeletal muscle atrophy reduces the QOL of patients and worsens life prognosis. Therefore, development of preventive therapy for muscle atrophy in hyperglycemic state is eagerly awaited. Juzentaihoto is a medicinal herb that has a function to supplement physical strength, and it is expected to prevent muscle atrophy. To determine the preventive effect of juzentaihoto on muscle atrophy in hyperglycemic state, streptozotocin (STZ) was administered to induce diabetes in mice and the preventive effect of juzentaihoto was evaluated. Mice that received juzentaihoto extract (JTT) showed that the decrease in muscle fiber cross-sectional area in the gastrocnemius muscle was reversed. Additionally, the expression level of tumor necrosis factor α (TNF-α), an inflammatory cytokine, in serum decreased, and that of ubiquitin ligase (atrogin-1, muscle RING-finger protein-1) mRNA in skeletal muscle decreased. An anti-inflammatory cytokine interleukin-10 showed increased levels in the serum and increased levels in spleen cell culture supernatant collected from mice that received JTT. JTT had no effect on the blood glucose level. These results suggest that prophylactic administration of JTT to STZ-induced diabetic mice affects immune cells such as in spleen, causing an anti-inflammatory effect and inhibiting excessive activation of the ubiquitin-proteasome system, to reverse muscle atrophy.


Assuntos
Anti-Inflamatórios/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Atrofia Muscular/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Glicemia/análise , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Medicamentos de Ervas Chinesas/farmacologia , Interleucina-10/sangue , Masculino , Camundongos Endogâmicos ICR , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/patologia , Proteínas Musculares/genética , Atrofia Muscular/sangue , Atrofia Muscular/genética , Atrofia Muscular/patologia , Proteínas Ligases SKP Culina F-Box/genética , Proteínas com Motivo Tripartido/genética , Fator de Necrose Tumoral alfa/sangue , Ubiquitina-Proteína Ligases/genética
12.
Biomed Pharmacother ; 117: 109053, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31176169

RESUMO

Chronic obstructive pulmonary disease (COPD) often causes diaphragm dysfunction, which is the main contributor to neuro-muscular respiratory failure and associated with the prognosis of COPD. However, the morphological changes in diaphragm during the development of COPD are complicated and underlying mechanisms have not been absolutely elucidated. Considering smoking is one of the most leading and important risk factors for development of COPD, we set out to investigate the effects of smoking on muscle fibre remodeling and underlying mechanisms in diaphragms. Rats were randomly exposed to cigarette smoke (CS) for one of three durations of 4, 8, and 12 weeks. CS exposure resulted in increased percentage of type I muscle fibres, enhanced apoptosis index, endoplasmic reticulum (ER) dilation, elevated expression of glucose-regulated protein 78, C/EBP homologous protein, caspase-12, peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), cytochrome c oxidase 4, Sdhb, p53 and a reduction in fibre diameters in rat diaphragms. The results indicated that CS exposure induced a shift to muscle fibres with aerobic metabolism in predominance in rat diaphragms, which may be dependent on the regulation of PGC-1α and p53. Additionally, ER stress (ERS) associated apoptosis may contribute to the pathogenesis of diaphragmatic muscle atrophy induced by CS exposure.


Assuntos
Diafragma/patologia , Fibras Musculares Esqueléticas/patologia , Fumar/efeitos adversos , Animais , Apoptose , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Enfisema/complicações , Enfisema/patologia , Retículo Endoplasmático/ultraestrutura , Estresse do Retículo Endoplasmático , Feminino , Mitocôndrias/metabolismo , Atrofia Muscular/patologia , Miosinas/metabolismo , Oxirredução , Pneumonia/complicações , Pneumonia/patologia , Ratos Sprague-Dawley , Fatores de Tempo , Proteína Supressora de Tumor p53/metabolismo
13.
Cells ; 8(6)2019 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-31208084

RESUMO

The maintenance of muscle mass and its ability to function relies on a bioenergetic efficient mitochondrial network. This network is highly impacted by fusion and fission events. We have recently shown that the acute deletion of the fusion protein Opa1 induces muscle atrophy, systemic inflammatory response, precocious epithelial senescence, and premature death that are caused by muscle-dependent secretion of FGF21. However, both fusion and fission machinery are suppressed in aging sarcopenia, cancer cachexia, and chemotherapy-induced muscle wasting. We generated inducible muscle-specific Opa1 and Drp1 double-knockout mice to address the physiological relevance of the concomitant impairment of fusion and fission machinery in skeletal muscle. Here we show that acute ablation of Opa1 and Drp1 in adult muscle causes the accumulation of abnormal and dysfunctional mitochondria, as well as the inhibition of autophagy and mitophagy pathways. This ultimately results in ER stress, muscle loss, and the reduction of force generation. However, the simultaneous inhibition of the fission protein Drp1 when Opa1 is absent alleviates FGF21 induction, oxidative stress, denervation, and inflammation rescuing the lethal phenotype of Opa1 knockout mice, despite the presence of any muscle weakness. Thus, the simultaneous inhibition of fusion and fission processes mitigates the detrimental effects of unbalanced mitochondrial fusion and prevents the secretion of pro-senescence factors.


Assuntos
Envelhecimento/patologia , GTP Fosfo-Hidrolases/metabolismo , Dinâmica Mitocondrial , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Animais , Autofagia , Dinaminas/deficiência , Dinaminas/metabolismo , Estresse do Retículo Endoplasmático , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo , GTP Fosfo-Hidrolases/deficiência , Camundongos Knockout , Mitocôndrias/patologia , Debilidade Muscular/complicações , Debilidade Muscular/patologia , Atrofia Muscular/complicações , Atrofia Muscular/patologia , Estresse Oxidativo , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise , Ubiquitina/metabolismo
14.
Crit Rev Oncol Hematol ; 141: 43-53, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31228648

RESUMO

Weight loss and depletion of nutritional status are frequent presentation hallmarks in non-small cell lung cancer (NSCLC). Decline in muscle mass is a major component in weight loss and may have both a prognostic and predictive value for survival and treatment-related toxicities. Recent findings suggest that weight and skeletal muscle mass gain during treatment may represent surrogate markers for outcome in advanced NSCLC patients. Herein we present an in-depth view of the impact of nutritional status derangements on NSCLC patients' outcome, focusing on lean body mass variations during disease course. We explored the impact of malnutrition with a major attention on novel treatment options. We reviewed molecular, metabolic and immunological mechanisms underlying muscle-wasting condition, which may exhibit a meaningful targeting potential. Incorporating a specialized and accurate body composition assessment into a comprehensive, patient-centered and tailored intervention will facilitate the achievement of nutritional goals and optimal care for lung cancer patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Músculo Esquelético/patologia , Estado Nutricional/fisiologia , Perda de Peso/fisiologia , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Composição Corporal/fisiologia , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/terapia , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/terapia , Músculo Esquelético/metabolismo , Atrofia Muscular/diagnóstico , Atrofia Muscular/etiologia , Atrofia Muscular/patologia , Prognóstico
15.
Biomed Res Int ; 2019: 7387131, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31061826

RESUMO

Background: Significant proportion of rotator cuff tears (RCTs) in clinical field are of a kind of repairable tear wherein the degree of fatty infiltration is of Goutallier stage 1 or stage 2. Therefore, the animal model, showing similar fatty infiltration, seems preferable for researches. The purpose of this study is to find out the proper time frame in which there is Goutallier stage 1 or stage 2 fatty infiltration in the rabbit RCT model for the research of repairable RCT in humans. Methods: Supraspinatus tendon tears were created in forty male New Zealand white rabbits at their right shoulder (n= 8 for each group), and a sham operation on the left shoulder. Rabbits were divided into five groups (2nd, 4th, 6th, 8th, and 12th weeks). Specimens were harvested from the central portion of the supraspinatus muscle for haematoxylin and eosin (H &E) staining, followed by histological and Goutallier grading evaluation. Results are expressed as mean ± standard deviation by Sigma Plot software (version 7.0). Results: At two weeks, mainly lipoblasts were observed around the muscle fibers, and at four weeks these lipoblasts were replaced by mature adipocytes with fatty infiltration amount (2.13 ± 0.35). The degree of muscle atrophy was (1.50 ± 0.53) at four weeks compared to sham group (0.88 ± 0.64) with significant difference (p < 0.05). The inflammatory process appeared as two phases. At two weeks, it was increased with grading value (1.88 ± 0.35). However, in the four-week group, it showed a sharp decrease (0.50 ± 0.53). At six weeks, inflammation reappeared to increase (1.13 ± 0.83). Then, a gradual decline appeared at eight weeks (0.88 ± 0.83) and at 12 weeks (0.50 ± 0.92). Conclusions: At two and four weeks, both fat distribution in rabbit supraspinatus muscles and Goutallier grading scale mostly appeared as grade 2. Therefore, we can consider four weeks to be a suitable period for making a repairable RCT animal model for the human research, considering the early acute tissue reaction at 2 weeks after the tendon tears.


Assuntos
Tecido Adiposo/metabolismo , Atrofia Muscular/metabolismo , Lesões do Manguito Rotador/metabolismo , Manguito Rotador/metabolismo , Tecido Adiposo/patologia , Animais , Modelos Animais de Doenças , Humanos , Masculino , Atrofia Muscular/etiologia , Atrofia Muscular/patologia , Coelhos , Manguito Rotador/patologia , Lesões do Manguito Rotador/patologia , Ombro/patologia , Fatores de Tempo
16.
Mar Drugs ; 17(5)2019 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-31083497

RESUMO

Dexamethasone (DEX), a synthetic glucocorticoid, causes skeletal muscle atrophy. This study examined the protective effects of Pyropia yezoensis peptide (PYP15) against DEX-induced myotube atrophy and its association with insulin-like growth factor-I (IGF-I) and the Akt/mammalian target of rapamycin (mTOR)-forkhead box O (FoxO) signaling pathway. To elucidate the molecular mechanisms underlying the effects of PYP15 on DEX-induced myotube atrophy, C2C12 myotubes were treated for 24 h with 100 µM DEX in the presence or absence of 500 ng/mL PYP15. Cell viability assays revealed no PYP15 toxicity in C2C12 myotubes. PYP15 activated the insulin-like growth factor-I receptor (IGF-IR) and Akt-mTORC1 signaling pathway in DEX-induced myotube atrophy. In addition, PYP15 markedly downregulated the nuclear translocation of transcription factors FoxO1 and FoxO3a, and inhibited 20S proteasome activity. Furthermore, PYP15 inhibited the autophagy-lysosomal pathway in DEX-stimulated myotube atrophy. Our findings suggest that PYP15 treatment protected against myotube atrophy by regulating IGF-I and the Akt-mTORC1-FoxO signaling pathway in skeletal muscle. Therefore, PYP15 treatment appears to exert protective effects against skeletal muscle atrophy.


Assuntos
Dexametasona/toxicidade , Fibras Musculares Esqueléticas/efeitos dos fármacos , Atrofia Muscular/tratamento farmacológico , Peptídeos/farmacologia , Proteínas de Plantas/farmacologia , Rodófitas/química , Animais , Autofagia/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Dexametasona/farmacologia , Proteínas Substratos do Receptor de Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Lisossomos/metabolismo , Camundongos , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patologia , Músculo Esquelético/efeitos dos fármacos , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Peptídeos/química , Proteínas de Plantas/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo
17.
Muscle Nerve ; 60(2): 192-201, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31093982

RESUMO

INTRODUCTION: We recently demonstrated the beneficial effects of 4-aminopyridine (4-AP), a potassium channel blocker, in enhancing remyelination and recovery of nerve conduction velocity and motor function after sciatic nerve crush injury in mice. Although muscle atrophy occurs very rapidly after nerve injury, the effect of 4-AP on muscle atrophy and intrinsic muscle contractile function is largely unknown. METHODS: Mice were assigned to sciatic nerve crush injury and no-injury groups and were followed for 3, 7, and 14 days with/without 4-AP or saline treatment. Morphological, functional, and transcriptional properties of skeletal muscle were assessed. RESULTS: In addition to improving in vivo function, 4-AP significantly reduced muscle atrophy with increased muscle fiber diameter and contractile force. Reduced muscle atrophy was associated with attenuated expression of atrophy-related genes and increased expression of proliferating stem cells. DISCUSSION: These findings provide new insights into the potential therapeutic benefits of 4-AP against nerve injury-induced muscle atrophy and dysfunction. Muscle Nerve 60: 192-201, 2019.


Assuntos
4-Aminopiridina/farmacologia , Lesões por Esmagamento/fisiopatologia , Músculo Esquelético/efeitos dos fármacos , Atrofia Muscular/patologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Bloqueadores dos Canais de Potássio/farmacologia , Remielinização/efeitos dos fármacos , Nervo Isquiático/efeitos dos fármacos , Animais , Lesões por Esmagamento/metabolismo , Lesões por Esmagamento/patologia , Proteína Forkhead Box O1/efeitos dos fármacos , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O3/efeitos dos fármacos , Proteína Forkhead Box O3/genética , Camundongos , Proteínas Musculares/efeitos dos fármacos , Proteínas Musculares/genética , Músculo Esquelético/inervação , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Atrofia Muscular/genética , Traumatismos dos Nervos Periféricos/genética , Traumatismos dos Nervos Periféricos/patologia , Regeneração/efeitos dos fármacos , Nervo Isquiático/lesões , Nervo Isquiático/patologia , Nervo Isquiático/fisiopatologia , Proteínas com Motivo Tripartido/efeitos dos fármacos , Proteínas com Motivo Tripartido/genética , Ubiquitina-Proteína Ligases/efeitos dos fármacos , Ubiquitina-Proteína Ligases/genética
18.
Anesthesiology ; 131(3): 569-579, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31094757

RESUMO

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: Muscle atrophy is common in the critically ill, and diaphragm atrophy occurs during mechanical ventilation. It is not known whether wasting of diaphragm and nondiaphragm muscle is related. WHAT THIS ARTICLE TELLS US THAT IS NEW: Ultrasound was used for serial assessment of diaphragm and pectoral muscle in 97 critically ill patients. Diaphragm and pectoral atrophy occurred in 48% and 29%, respectively, and was associated with septic shock (diaphragm) and steroid use (pectoral); atrophy of the two muscle types appears unrelated. BACKGROUND: Muscle atrophy occurs early during critical illnesses. Although diffuse, this atrophy may specifically affect the diaphragm under artificial inactivity accompanying invasive mechanical ventilation. The primary objective of this study was to highlight diaphragm atrophy during the first 5 days of critical illness. Monitoring of pectoral thickness (a nonpostural muscle with mainly phasic function) served as a control. METHODS: Diaphragm and pectoral thicknesses were measured by ultrasound within the first 24 h of admission in 97 critically ill patients, including 62 on mechanical ventilation. Thirty-five patients were reexamined at day 5. RESULTS: Baseline median (interquartile) values of diaphragm and pectoral thicknesses at day 1 were 2.4 (2.0, 2.9) and 5.9 (4.7, 7.2) mm, respectively (n = 97). Higher values of diaphragm thickness at baseline were positively associated with male sex, chronic obstructive pulmonary disease, and diabetes. Diaphragm and pectoral atrophies (defined as a decrease of 10% or more between day 1 and day 5) were detected in 48% (17 of 35) and 29% (10 of 34) respectively, and were uncorrelated with each other. Diaphragm atrophy was significantly more frequent in patients with septic shock and in those with mechanical ventilation, as compared with their respective counterparts (71% [10 of 14] vs. 33% [7 of 21], P = 0.027 and 71% [17 of 28] vs. 0% [0 of 7], P = 0.004, respectively), whereas pectoral atrophy was more common in patients treated with steroids as compared with their counterparts (58% [7 of 12] vs. 14% [3 of 22], P = 0.006). A statistically significant association between diaphragm atrophy and outcome was not found. Pectoral atrophy seemed associated with less successful weaning from mechanical ventilation at day 14 (12% [1 of 8] vs. 58% [11 of 19], P = 0.043). CONCLUSIONS: Ultrasound enables identification of specific early diaphragm atrophy that affects the majority of mechanically ventilated patients and septic shock patients. Diaphragm atrophy and pectoral muscle atrophy seem to be two unrelated processes.


Assuntos
Diafragma/diagnóstico por imagem , Diafragma/patologia , Atrofia Muscular/diagnóstico por imagem , Atrofia Muscular/patologia , Músculos Peitorais/diagnóstico por imagem , Músculos Peitorais/patologia , Idoso , Estado Terminal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Respiração Artificial , Ultrassonografia/métodos
19.
Med Hypotheses ; 127: 91-96, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31088657

RESUMO

HYPOTHESIS: The hypothesis of this work is that infrared thermography could become a valid tool for the diagnosis and follow-up of the Emery-Dreifuss disease due to putative temperature changes produced by a constant degenerative evolution of this muscular dystrophy. TESTING THE HYPOTHESIS: To justify this hypothesis we proposed a pilot study with 2 brothers affected of Emery-Dreifuss who present a very different age, with the principal objective to evidence a possible evolution of this pathology. Acquisition and comparison of images of computerized axial tomography (CT) and thermography (IRT) of the distal limbs in 2 affected brothers. DATA AND DISCUSSION: Important image correlations in the region of the thighs and the posterior region of the legs have been highlighted. The comparison between the CT and the thermography showed how the first results are encouraged and promising and open a possible new line of research on the evaluation and follow-up of this disease. Despite this, a larger number of studies are needed to validate the thermography as a diagnostic technique and follow-up of this pathology.


Assuntos
Músculo Esquelético/fisiopatologia , Distrofia Muscular de Emery-Dreifuss/diagnóstico , Termografia/métodos , Temperatura Corporal , Desfibriladores , Seguimentos , Humanos , Processamento de Imagem Assistida por Computador/métodos , Raios Infravermelhos , Imagem por Ressonância Magnética , Masculino , Proteínas de Membrana/metabolismo , Atrofia Muscular/patologia , Distrofia Muscular de Emery-Dreifuss/fisiopatologia , Distrofia Muscular de Emery-Dreifuss/terapia , Mutação , Proteínas Nucleares/metabolismo , Oscilometria , Projetos Piloto , Tomografia Computadorizada por Raios X , Adulto Jovem
20.
Chem Biol Interact ; 306: 70-77, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30980806

RESUMO

PURPOSE: Skeletal muscle is severely affected in diabetes leading to muscle atrophy. Previously we reported the role of ER stress in muscle atrophy due to hyperglycemia. Hence, in the present study, we investigated the effect of a classical ER stress inhibitor, 4-phenylbutyric acid (PBA), on muscle atrophy in diabetic rats. METHODS: Diabetes was induced in male rats by streptozotocin, and PBA was administered (40 mg/kg/day; intraperitoneal) after two months of diabetes for two more months. Gastrocnemius muscle is collected after four months of experimental period. The cross-sectional area of myocytes was measured on Hematoxylin and Eosin stained muscle sections. Protein levels of ER stress markers, ubiquitin-proteasome system (UPS) components, and apoptosis were analysed by immunoblot. Proteasomal activity and apoptotic cells were measured. RESULTS: ER stress markers (GRP78, ATF6, ATF4 and CHOP) that are elevated in diabetes are decreased with PBA treatment. PBA also averted diabetes-induced alterations in UPS (higher levels of E1, atrogin-1, UCHL1 and UCHL5, accumulation of ubiquitinated proteins and increased proteasomal activity). Apoptosis mediators-p53, BAX, and cleaved caspase-3 protein levels, and TUNEL positive cells were decreased in PBA treated diabetic rats. PBA notably improved the muscle-cross sectional area. CONCLUSIONS: Results highlighted the therapeutic potential of PBA in diabetes muscle wastage.


Assuntos
Diabetes Mellitus Experimental/prevenção & controle , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Atrofia Muscular/prevenção & controle , Fenilbutiratos/farmacologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Ubiquitina/metabolismo , Animais , Apoptose/efeitos dos fármacos , Biomarcadores/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/patologia , Injeções Intraperitoneais , Masculino , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/patologia , Fenilbutiratos/administração & dosagem , Ratos , Ratos Sprague-Dawley , Estreptozocina
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA