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1.
Medicine (Baltimore) ; 99(24): e20310, 2020 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-32541454

RESUMEN

RATIONALE: Mitochondrial encephalomyopathy with lactic acidosis and stroke- like episodes (MELAS) syndrome is caused by mitochondrial respiratory chain dysfunction and oxidative phosphorylation disorder. It is a rare clinical metabolic disease involved with multiple systems. PATIENT CONCERNS: A 22-year-old patient presented with limb convulsion accompanied by loss of consciousness, headache, partial blindness, blurred vision, and so on. DIAGNOSES: Brain magnetic resonance imaging showed a high-intensity area in bilateral occipital cortex, left parietal lobe and cerebellum on diffusion-weighted imaging. These focus did not distribute as vascular territory. The pathological examination of skeletal muscle revealed several succinate dehydrogenase reactive vessels with overreaction and increased content of lipid droplets in some muscle fibers. Genetic testing showed that the patient carried m.10158T>C mutation. INTERVENTIONS: She was provided with traditional arginine hydrochloride therapy and orally medication of coenzyme Q (10 mg). OUTCOMES: Mitochondrial DNA of blood and hair follicle of patient carried m.10158T>C mutation LESSONS:: For the suspected patients of MELAS syndrome, if the hot-spot mutation test is negative, more detection sites should be selected.


Asunto(s)
Acidosis Láctica/complicaciones , ADN Mitocondrial/genética , Síndrome MELAS/genética , Accidente Cerebrovascular/etiología , Administración Oral , Arginina/administración & dosificación , Arginina/uso terapéutico , Concienciación , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Femenino , Humanos , Síndrome MELAS/diagnóstico por imagen , Síndrome MELAS/tratamiento farmacológico , Síndrome MELAS/patología , Imagen por Resonancia Magnética/métodos , Micronutrientes/administración & dosificación , Micronutrientes/uso terapéutico , Encefalomiopatías Mitocondriales/diagnóstico , Encefalomiopatías Mitocondriales/etiología , Encefalomiopatías Mitocondriales/patología , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Mutación , Accidente Cerebrovascular/diagnóstico , Succinato Deshidrogenasa/metabolismo , Ubiquinona/administración & dosificación , Ubiquinona/uso terapéutico , Adulto Joven
2.
Gene ; 752: 144765, 2020 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-32413480

RESUMEN

The natural flight response in shrimp is powered by rapid contractions of the abdominal muscle fibres to propel themselves backwards away from perceived danger. This muscle contraction is dependent on repetitive depolarization of muscle plasma membrane, triggering tightly spaced cytoplasmic [Ca2+] transients and rapidly rising tetanic force responses. To achieve such high amplitude and high frequency of Ca2+ transients requires a high abundance of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) to rapidly clear cytoplasmic Ca2+ between each transient and an efficient Ca2+ release system consisting of the Ryanodine Receptor (RyR), and voltage gated Ca2+ channels (CaVs). With the aim to expand our knowledge of muscle gene function and identify orthologous genes regulating muscle excitation-contraction (EC) coupling, this study assembled nine Penaeid shrimp muscle transcriptomes. On average, the nine transcriptomes contained 27,000 contigs, with an annotation rate of 36% and a BUSCO completeness of 70%. Despite maintaining their function, the crustacean RyR and CaV proteins showed evidence of significant diversification from mammalian orthologs, while SERCA remained more conserved. Several key components of protein interaction were conserved, while others showed distinct crustacean specific evolutionary adaptations. Lastly, this study revealed approximately 1,000 orthologous genes involved in muscle specific processes present across all nine species.


Asunto(s)
Acoplamiento Excitación-Contracción/genética , Penaeidae/genética , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/genética , Animales , Evolución Biológica , Calcio/metabolismo , Canales de Calcio Tipo L/metabolismo , Señalización del Calcio/fisiología , Citosol/metabolismo , Evolución Molecular , Contracción Muscular/fisiología , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Canal Liberador de Calcio Receptor de Rianodina/genética , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/metabolismo , Especificidad de la Especie , Transcriptoma/genética
3.
Gene ; 752: 144782, 2020 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-32442577

RESUMEN

The branched-chain amino acids (BCAA) play an important role in muscle energy metabolism, and Krüppel-like factor 15 (KLF15) is an essential regulator of BCAA metabolism in muscle under nutritional deficiency. In this study, we analyzed the effect of normal feeding (starvation for 0 day), starvation for 3, 7, 10, 15 days, and refeeding for 7 days after 15 days of starvation on the expression of KLF15 and BCAA metabolism in muscle of Chinese soft-shelled turtles by a fasting-refeeding trial. The results showed that the level of KLF15 transcription was increased first and then decreased in muscle during short-term starvation, and the protein level was gradually increased. Both the mRNA and protein level of the KLF15 returned to normal feeding level after refeeding for 7 days. The changing trend of the activities of branched-chain aminotransferase (BCAT) and alanine aminotransferase (ALT) was consistent to that of KLF15 mRNA, but at the transcription level, the expression of BCAT mRNA was consistent with the change of enzyme activity as well as ALT continued to increase in muscle under starvation. In addition, BCAA content showed a trend that decreased first and then increased under starvation, while the alanine (Ala) was the contrary. The above results indicated that the regulatory role of KLF15 in BCAA catabolism of muscle in Chinese soft-shelled turtles under nutritional deficiency, which might be activated the catabolism of BCAA in muscle to provide energy and maintain the homeostasis by KLF15-BACC signaling axis.


Asunto(s)
Aminoácidos de Cadena Ramificada/metabolismo , Factores de Transcripción de Tipo Kruppel/metabolismo , Músculo Esquelético/metabolismo , Alanina Transaminasa/metabolismo , Aminoácidos de Cadena Ramificada/genética , Animales , Metabolismo Energético/fisiología , Ayuno , Factores de Transcripción de Tipo Kruppel/genética , Músculos/metabolismo , Transducción de Señal/fisiología , Inanición/metabolismo , Tortugas/genética , Tortugas/metabolismo
5.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(1): 104-109, 2020 Jan 30.
Artículo en Chino | MEDLINE | ID: mdl-32376563

RESUMEN

OBJECTIVE: To investigate the changes of skeletal muscle mass and strength and the expressions of matrix metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinases-1 (TIMP-1) and collagen-1 in the skeletal muscle of aged rats with sarcopenia. METHODS: With 11 young (6-month-old) SD rats as control group, 18 aged (25-month-old) SD rats were divided into two groups (n=9) according to the relative lean mass determined dual X-ray absorptiometry (DXA), namely aged control group and aged sarcopenia group (the relative lean mass was 2SD higher in aged control than in aged sarcopenia group. The forelimb grip strength of the rats was measured using an electronic grip strength meter. The extracellular matrix (ECM) of the rat's gastrocnemius was observed with HE staining and sirius Red staining, and the protein expressions of collagen-1, MMP-1, and TIMP-1 in the muscular tissues were detected with Western blotting. RESULTS: Compared with the young rats, the aged control rats had significantly lower relative grip strength (P < 0.01) and increased expressions of collagen-1 and TIMP-1 (P < 0.05) and ECM content in the skeletal muscles, but the relative lean mass and MMP-1 protein expression were comparable between the two groups (P>0.05). Compared with the aged control rats, the aged sarcopenic rats had significantly lowered relative lean mass (P < 0.01) and MMP-1 expressions of (P < 0.05) and increased expressions of collagen-1 and TIMP-1 proteins and ECM content in the muscular tissues (P < 0.05) without significant changes in the relative grip strength (P>0.05). CONCLUSIONS: MMP-1/TIMP-1 imbalance in the skeletal muscle during aging affects ECM metabolism and leads to increased collagen fibers, which in turn affects the skeletal muscle mass and function and contribute to the onset of sarcopenia.


Asunto(s)
Envejecimiento , Metaloproteinasa 1 de la Matriz/metabolismo , Músculo Esquelético/metabolismo , Sarcopenia/metabolismo , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Animales , Metaloproteinasa 13 de la Matriz , Músculo Esquelético/patología , Ratas , Ratas Sprague-Dawley
6.
Science ; 368(6490)2020 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-32355002

RESUMEN

Repeated bouts of exercise condition muscle mitochondria to meet increased energy demand-an adaptive response associated with improved metabolic fitness. We found that the type 2 cytokine interleukin-13 (IL-13) is induced in exercising muscle, where it orchestrates metabolic reprogramming that preserves glycogen in favor of fatty acid oxidation and mitochondrial respiration. Exercise training-mediated mitochondrial biogenesis, running endurance, and beneficial glycemic effects were lost in Il13-/- mice. By contrast, enhanced muscle IL-13 signaling was sufficient to increase running distance, glucose tolerance, and mitochondrial activity similar to the effects of exercise training. In muscle, IL-13 acts through both its receptor IL-13Rα1 and the transcription factor Stat3. The genetic ablation of either of these downstream effectors reduced running capacity in mice. Thus, coordinated immunological and physiological responses mediate exercise-elicited metabolic adaptations that maximize muscle fuel economy.


Asunto(s)
Adaptación Fisiológica/inmunología , Glucógeno/metabolismo , Interleucina-13/metabolismo , Mitocondrias Musculares/metabolismo , Músculo Esquelético/metabolismo , Resistencia Física/inmunología , Animales , Glucemia/metabolismo , Línea Celular , Ácidos Grasos/metabolismo , Femenino , Humanos , Interleucina-13/sangre , Interleucina-13/genética , Subunidad alfa1 del Receptor de Interleucina-13/genética , Subunidad alfa1 del Receptor de Interleucina-13/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mioblastos/metabolismo , Oxidación-Reducción , Condicionamiento Físico Animal , Carrera , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo
7.
Food Chem ; 321: 126677, 2020 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-32247180

RESUMEN

Myosin heavy chain (MHC) isoforms in goat muscles and their possible relationships with meat quality have not been fully elucidated. This study characterized the MHC isoforms in different caprine muscles using sodium dodecyl sulphate glycerol gel electrophoresis (SDS-GGE). The relationships between MHC isoforms, calpain systems and meat quality characteristics of different muscles in goats were examined. Four muscles, namely infraspinatus (IF), longissimus dorsi (LD), psoas major (PM) and supraspinatus (SS) were obtained from ten Boer crossbred bucks (7-10 months old; 26.5 ± 3.5 kg, BW). The percentages of MHC I, MHC IIa and MHC IIx in SS, IF, PM and LD were 47.2, 38.3, 32.1, 11.9; 28.0, 42.1, 33.0, 36.4; and 24.8, 19.6, 34.9 and 51.7, respectively. IF and SS had higher levels of calpastatin, total collagen and insoluble collagen contents than did PM and LD. PM had longer sarcomere length than did other muscles. LD had higher collagen solubility, troponin-T degradation products and glycogen content than did other muscles. These results infer that variable fiber-type composition could account partially for the differences in the physicochemical properties of goat muscles.


Asunto(s)
Calpaína/metabolismo , Músculo Esquelético/metabolismo , Cadenas Pesadas de Miosina/metabolismo , Animales , Proteínas de Unión al Calcio/metabolismo , Electroforesis , Electroforesis en Gel de Poliacrilamida , Cabras , Carne/análisis , Músculo Esquelético/química , Isoformas de Proteínas/metabolismo , Troponina T/metabolismo
8.
Life Sci ; 251: 117603, 2020 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-32240680

RESUMEN

AIMS: The objective of this study was to establish a more accurate analytical model and method for grip strength test of mice and to investigate the beneficial effects of lifelong exercise training to prevent functional decline of muscle during aging. MAIN METHODS: Fifty randomly selected adult male BALB/c mice (24-56 week age) were used in grip strength testing periodically with short periods (3 s). Such method was used to detect a modified grip strength test. Then sixty-four male BALB/c mice (6 week age) were assigned into groups Sedentary (n = 32), Exercise (n = 32, lifelong treadmill training 3 days per week and 30 min per day). The muscle strength and morphology parameters were measured at the ages of 6, 12, 30 and 64 weeks, respectively. KEY FINDINGS: The grip strength (peak value and endurance) of sedentary group monotonically decreased in adult BALB/c mice during aging, while that of exercise group remained a relatively high level even slightly increased at aged period. Meanwhile, lifelong exercise training could slow down the loss of gastrocnemius muscle mass, myofiber cross-sectional area, myonuclear number and myonuclear domain. The number of myofibers was relatively stable in adult mice. SIGNIFICANCE: Modified analytical method for grip strength testing, with improved accuracy and reliability, may be an efficient substitute for conventional method in measuring the strength and endurance of mice and investigating the effect of lifelong exercise on muscle loss. Lifelong exercise training helps prevent muscle loss and muscle defunctionalization while aging.


Asunto(s)
Envejecimiento/fisiología , Fuerza Muscular/fisiología , Condicionamiento Físico Animal/fisiología , Conducta Sedentaria , Animales , Masculino , Ratones , Ratones Endogámicos BALB C , Fibras Musculares Esqueléticas/fisiología , Músculo Esquelético/metabolismo , Reproducibilidad de los Resultados
9.
Food Chem ; 319: 126559, 2020 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-32197215

RESUMEN

Postmortem biochemical properties (pH, salt solubility, Ca2+-ATPase activity, ATP-related compounds) and microstructural changes in the striated adductor muscle of pre-rigor frozen Japanese scallops (Patinopecten yessoensis) were studied after thawing and during storage at 4℃. Four thawing methods were used: running water (18℃, R); ice-water (0℃, I); air (4℃, A) and ice-saltwater (-2℃, S). The pH values and salt solubility of R group were lower than the other three thawing groups while I group was highest after thawing. However, no significant difference (P < 0.05) in Ca2+-ATPase activity were detected among 4 groups. The microstructure results indicated that the structure of I group was close to that of fresh scallop. Moreover, ATP decomposition rate was the slowest. Therefore, ice-water thawing is the best method because it induced the least changes in the biochemical properties and microstructures of scallop adductor muscle.


Asunto(s)
Músculo Esquelético/química , Pectinidae/química , Animales , Fenómenos Bioquímicos , Congelación , Músculo Esquelético/metabolismo , Pectinidae/metabolismo , Alimentos Marinos , Solubilidad
10.
PLoS One ; 15(3): e0230083, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32160266

RESUMEN

Duchenne Muscular Dystrophy (DMD) is a severe muscle-wasting disease caused by mutations in the DMD gene encoding dystrophin, expressed mainly in muscles but also in other tissues like retina and brain. Non-progressing cognitive dysfunction occurs in 20 to 50% of DMD patients. Furthermore, loss of expression of the Dp427 dystrophin isoform in the brain of mdx mice, the most used animal model of DMD, leads to behavioral deficits thought to be linked to insufficiencies in synaptogenesis and channel clustering at synapses. Mdx mice where the locomotor phenotype is mild also display a high and maladaptive response to stress. Recently, we generated Dmdmdx rats carrying an out-of frame mutation in exon 23 of the DMD gene and exhibiting a skeletal and cardiac muscle phenotype similar to DMD patients. In order to evaluate the impact of dystrophin loss on behavior, we explored locomotion parameters as well as anhedonia, anxiety and response to stress, in Dmdmdx rats aged from 1.5 to 7 months, in comparison to wild-type (WT) littermates. Pattern of dystrophin expression in the brain of WT and Dmdmdx rats was characterized by western-blot analyses and immunohistochemistry. We showed that dystrophin-deficient Dmdmdx rats displayed motor deficits in the beam test, without association with depressive or anxiety-like phenotype. However, Dmdmdx rats exhibited a strong response to restraint-induced stress, with a large increase in freezings frequency and duration, suggesting an alteration in a functional circuit including the amygdala. In brain, large dystrophin isoform Dp427 was not expressed in mutant animals. Dmdmdx rat is therefore a good animal model for preclinical evaluations of new treatments for DMD but care must be taken with their responses to mild stress.


Asunto(s)
Encéfalo/metabolismo , Distrofina/genética , Distrofia Muscular Animal/patología , Animales , Ansiedad/patología , Sistema Nervioso Central/metabolismo , Distrofina/deficiencia , Distrofina/metabolismo , Locomoción , Aprendizaje por Laberinto , Ratones Endogámicos mdx , Músculo Esquelético/metabolismo , Miocardio/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Ratas , Ratas Transgénicas , Estrés Psicológico
11.
PLoS One ; 15(3): e0229933, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32191723

RESUMEN

PURPOSE: Creatine Kinase (CK) reaction plays an important role in energy metabolism and estimate of its reaction rate constant in heart provides important insight into cardiac energetics. Fast saturation transfer method ([Formula: see text] nominal) to measure CK reaction rate constant (kf) was previously demonstrated in open chest swine hearts. The goal of this work is to further develop this method for measuring the kf in human myocardium at 7T. [Formula: see text] approach is combined with 1D-ISIS/2D-CSI for in vivo spatial localization and myocardial CK forward rate constant was then measured in 7 volunteers at 7T. METHODS: [Formula: see text] method uses two partially relaxed saturation transfer (ST) spectra and correction factor to determine CK rate constant. Correction factor is determined by numerical simulation of Bloch McConnell equations using known spin and experimental parameters. Optimal parameters and error estimate in calculation of CK reaction rate constant were determined by simulations. The technique was validated in calf muscles by direct comparison with saturation transfer measurements. [Formula: see text] pulse sequence was incorporated with 1D-image selected in vivo spectroscopy, combined with 2D-chemical shift spectroscopic imaging (1D-ISIS/2D-CSI) for studies in heart. The myocardial CK reaction rate constant was then measured in 7 volunteers. RESULTS: Skeletal muscle kf determined by conventional approach and [Formula: see text] approach were the same 0.31 ± 0.02 s-1 and 0.30 ± 0.04 s-1 demonstrating the validity of the technique. Results are reported as mean ± SD. Myocardial CK reaction rate constant was 0.29 ± 0.05 s-1, consistent with previously reported studies. CONCLUSION: [Formula: see text] method enables acquisition of 31P saturation transfer MRS under partially relaxed conditions and enables 2D-CSI of kf in myocardium. This work enables applications for in vivo CSI imaging of energetics in heart and other organs in clinically relevant acquisition time.


Asunto(s)
Creatina Quinasa/aislamiento & purificación , Creatina/metabolismo , Corazón/diagnóstico por imagen , Músculo Esquelético/enzimología , Adenosina Trifosfato/metabolismo , Adulto , Creatina Quinasa/metabolismo , Metabolismo Energético/fisiología , Femenino , Corazón/fisiología , Humanos , Cinética , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética , Masculino , Músculo Esquelético/metabolismo , Miocardio/enzimología , Miocardio/patología , Isótopos de Fósforo/química
12.
PLoS One ; 15(3): e0230737, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32210454

RESUMEN

Studying the time course of gene expression in injured skeletal muscle would help to estimate the timing of injuries. In this study, we investigated large-scale gene expression in incision-injured mouse skeletal muscle by DNA microarray using correspondence analysis (CA). Biceps femoris muscle samples were collected 6, 12, and 24 hours after injury, and RNA was extracted and prepared for microarray analysis. On a 2-dimensional plot by CA, the genes (row score coordinate) located farther from each time series (column score coordinate) had more upregulation at particular times. Each gene was situated in 6 subdivided triangular areas according to the magnitude of the relationship of the fold change (FC) value at each time point compared to the control. In each area, genes for which the ratios of two particular FC values were close to 1 were distributed along the two border lines. There was a tendency for genes whose FC values were almost equal to be distributed near the intersection of these 6 areas. Therefore, the gene marker candidates for estimation of the timing of injuries were detectable according to the location on the CA plot. Moreover, gene sets created by a specific gene and its surrounding genes were composed of genes that showed similar or identical fluctuation patterns to the specific gene. In various analyses on these sets, significant gene ontology term and pathway activity may reflect changes in specific genes. In conclusion, analyses of gene sets based on CA plots is effective for investigation of the time-dependent fluctuation in gene expression after injury.


Asunto(s)
Perfilación de la Expresión Génica/métodos , Músculo Esquelético/lesiones , Músculo Esquelético/metabolismo , Animales , Ontología de Genes , Masculino , Ratones , Ratones Endogámicos BALB C , Análisis de Secuencia por Matrices de Oligonucleótidos , Factores de Tiempo
13.
Braz J Med Biol Res ; 53(3): e8969, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32130291

RESUMEN

This study investigated the repercussions of adjuvant-induced arthritis (AIA) on body composition and the structural organization of the soleus and cardiac muscles, including their vascularization, at different times of disease manifestation. Male rats were submitted to AIA induction by intradermal administration of 100 µL of Mycobacterium tuberculosis (50 mg/mL), in the right hind paw. Animals submitted to AIA were studied 4 (AIA4), 15 (AIA15), and 40 (AIA40) days after AIA induction as well as a control group of animals not submitted to AIA. Unlike the control animals, AIA animals did not gain body mass throughout the evolution of the disease. AIA reduced food consumption, but only on the 40th day after induction. In the soleus muscle, AIA reduced the wet mass in a time-dependent manner but increased the capillary density by the 15th day and the fiber density by both 15 and 40 days after induction. The diameter of the soleus fiber decreased from the 4th day after AIA induction as well as the capillary/fiber ratio, which was most evident on the 40th day. Moreover, AIA induced slight histopathological changes in the cardiac muscle that were more evident on the 15th day after induction. In conclusion, AIA-induced changes in body composition as well as in the soleus muscle fibers and vasculature have early onset but are more evident by the 15th day after induction. Moreover, the heart may be a target organ of AIA, although less sensitive than skeletal muscles.


Asunto(s)
Artritis Experimental/patología , Composición Corporal , Músculo Esquelético/patología , Miocardio/patología , Animales , Artritis Experimental/metabolismo , Modelos Animales de Enfermedad , Masculino , Músculo Esquelético/metabolismo , Miocardio/metabolismo , Ratas
14.
Food Chem ; 319: 126571, 2020 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-32169769

RESUMEN

This study aims to investigate the changes in mitochondrial apoptotic factors and proteolysis of two porcine muscles (psoas major - PM and longissimus dorsi - LD) during aging. Results found that during 2-168 h postmortem mitochondrial membrane permeability, mitochondrial lipid peroxidation, Ca2+ levels were increased, while the reduction level and abundance of cytochrome c were decreased (P < 0.05) in both muscle types. Furthermore, the activation of caspase-3 along with increases in troponin-T and desmin degradation, and µ-calpain autolysis were found (P < 0.05), regardless of muscle type. PM maintained higher mitochondrial apoptotic factors, but had more intact desmin, less troponin-T degradation and less extent of autolyzed products of µ-calpain compared to LD (P < 0.05). These results indicate that the rapid onset of mitochondrial apoptosis of PM would not lead to a subsequent impact on myofibrillar protein degradation, suggesting that the mitochondrial apoptosis mediated tenderization process could be muscle-specific.


Asunto(s)
Apoptosis , Mitocondrias/metabolismo , Músculo Esquelético/metabolismo , Carne Roja , Animales , Autólisis/metabolismo , Calpaína/metabolismo , Desmina/metabolismo , Miofibrillas/metabolismo , Proteolisis , Porcinos , Factores de Tiempo , Troponina T/metabolismo
15.
Life Sci ; 250: 117549, 2020 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-32179073

RESUMEN

AIM: To evaluate physical fitness and cardiovascular effects in rats with renovascular hypertension, two kidneys, one clip (2K1C) submitted to voluntary exercise (ExV). MAIN METHODS: 24 h after surgery (SHAM and 2K1C) rats were submitted to ExV for one week (adaptation). ExV adherent rats were separated into exercise (2K1C-EX and SHAM-EX) or sedentary (2K1C-SED and SHAM-SED) groups. After 4 weeks, exhaustion test, plasma lactate, cardiovascular parameters were evaluated and gastrocnemius muscle was removed for evaluation of gene expression of muscle metabolism markers (PGC1α; AMPK, SIRT-1, UCP-3; MCP-1; LDH) and of the redox process. KEY FINDINGS: ExV decreased blood lactate concentration and increased SOD and CAT activity and a SIRT-1 and UCP-3 gene expression in the gastrocnemius muscle of 2K1C-ExV rats compared to 2K1C-SED rats. Gene expressions of PGC1α, UCP-3, MCT-1, AMPK were higher in 2K1C-ExV rats compared to SHAM-SED rats. Blood pressure in 2K1C-ExV was lower compared to 2K1C-SED and higher in SHAM-SED rats. Reflex bradycardia in 2K1C-EX rats increased compared to 2K1C-SED and was similar to SHAM-SED. The variation in mean blood pressure induced by ganglion blocker hexamethonium and Ang II AT1 receptor antagonist, losartan in the 2K1C-ExV rats was smaller compared to the 2K1C-SED rats and it was similar to the SHAM-SED rats. SIGNIFICANCE: O ExV induced adaptive responses in 2K1C-ExV rats by decreasing sympathetic and Ang II activities and stimulating intracellular signaling that favors redox balance and reduced blood lactate concentration. These adaptive responses, then, contribute to reduced arterial pressure, improved baroreflex sensitivity and physical fitness of 2K1C rats.


Asunto(s)
Hipertensión Renovascular/metabolismo , Músculo Esquelético/metabolismo , Condicionamiento Físico Animal , Transducción de Señal , Animales , Barorreflejo/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Bradicardia , Modelos Animales de Enfermedad , Frecuencia Cardíaca/efectos de los fármacos , Riñón/efectos de los fármacos , Losartán/farmacología , Masculino , Oxidación-Reducción , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Ratas , Ratas Endogámicas F344 , Sirtuina 1/metabolismo , Sistema Nervioso Simpático/efectos de los fármacos , Proteína Desacopladora 3/metabolismo
17.
PLoS One ; 15(3): e0226860, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32119683

RESUMEN

The mitochondrial theory of aging attributes much of the aging process to mitochondrial DNA damage. The polymerase gamma (PolG) mutant mouse was designed to evaluate this theory and thus carries a mutated proofreading region of polymerase gamma (D257A) that exclusively transcribes the mitochondrial genome. As a result, PolGD257A mice accumulate mitochondrial DNA (mtDNA) mutations that lead to premature aging, as evidenced by hair loss, weight loss, kyphosis, increased rates of apoptosis, organ damage, and an early death, occurring around 12 months of age. Research has shown that exercise decreases skeletal muscle mtDNA mutations and normalizes protein levels in PolG mice. However, brain mtDNA changes with exercise in PolG mice have not been studied. We found no effects of exercise on mtDNA mutations or copy number in either the brain or liver of PolG mice, despite changes to body mass. Our results suggest that mitochondrial mutations play little role in exercise-brain interactions in the PolG model of accelerated aging. In addition to evaluating the effect of exercise on mtDNA outcomes, we also implemented novel methods for both extracting mtDNA and measuring mtDNA mutations, with aims for improving the efficiency and accuracy of these methods.


Asunto(s)
Envejecimiento Prematuro/prevención & control , Daño del ADN/fisiología , Polimerasa del ADN Mitocondrial/genética , ADN Mitocondrial/genética , Condicionamiento Físico Animal/fisiología , Envejecimiento Prematuro/genética , Envejecimiento Prematuro/patología , Envejecimiento Prematuro/fisiopatología , Animales , Encéfalo/citología , Encéfalo/metabolismo , Encéfalo/patología , Variaciones en el Número de Copia de ADN , Polimerasa del ADN Mitocondrial/metabolismo , ADN Mitocondrial/aislamiento & purificación , ADN Mitocondrial/metabolismo , Modelos Animales de Enfermedad , Humanos , Hígado/citología , Hígado/metabolismo , Hígado/patología , Masculino , Ratones , Ratones Transgénicos , Músculo Esquelético/citología , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Mutación
18.
Artículo en Inglés | MEDLINE | ID: mdl-32062368

RESUMEN

This study investigated lipid alterations in muscle tissues [gastrocnemius (Gas) and soleus (Sol)] of mice under different diet programs (weight gain, weight maintenance, weight regain, and controls) by nanoflow ultrahigh pressure liquid chromatography-electrospray ionization-tandem mass spectrometry. Since overloaded lipids in the skeletal muscle tissues by excessive fat accumulation are related to insulin resistance leading to type II diabetes mellitus, analysis of lipid alteration in muscle tissues with respect to high-fat diet (HFD) is important to understand obesity related diseases. A total of 345 individual lipid species were identified with their molecular structures, and 184 lipids were quantified by selected reaction monitoring method. Most triacylglycerol (TG) and phosphatidylethanolamine (PE) species displayed a significant (>2-fold, p < 0.01) increase in both the Gas and Sol and to a larger degree in the Gas. However, lipid classes involved in insulin resistance and anti-inflammatory response, including lysophosphatidylcholine (18:0), diacylglycerol (16:0_18:1, 16:0_18:2, and 18:1_18:1), ceramide (d18:1/24:0 and d18:1/24:1), and phosphatidylinositol (18:0/20:4), showed a significant accumulation in the Sol exclusively after HFD treatment. In addition, the lipid profiles were not significantly altered in mice that were fed HFD only for the last 4 weeks (weight gain group), suggesting that consuming HFD in the younger age period can be more effective in the Gas. This study reveals that lipid classes related to insulin resistance accumulated more in the Sol than in the Gas following HFD treatment and the weight regain program perturbed lipid profiles of the Sol to a greater extent than that by the other diet programs, confirming that the Sol tissue is more influenced by HFD than Gas.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Dieta Alta en Grasa , Lípidos/análisis , Músculo Esquelético/química , Espectrometría de Masas en Tándem/métodos , Animales , Límite de Detección , Masculino , Ratones , Ratones Endogámicos C57BL , Músculo Esquelético/metabolismo , Aumento de Peso/fisiología
19.
PLoS One ; 15(2): e0223340, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32053588

RESUMEN

The Rab GTPase activating protein known as Akt substrate of 160 kDa (AS160 or TBC1D4) regulates insulin-stimulated glucose uptake in skeletal muscle, the heart, and white adipose tissue (WAT). A novel rat AS160-knockout (AS160-KO) was created with CRISPR/Cas9 technology. Because female AS160-KO versus wild type (WT) rats had not been previously evaluated, the primary objective of this study was to compare female AS160-KO rats with WT controls for multiple, important metabolism-related endpoints. Body mass and composition, physical activity, and energy expenditure were not different between genotypes. AS160-KO versus WT rats were glucose intolerant based on an oral glucose tolerance test (P<0.001) and insulin resistant based on a hyperinsulinemic-euglycemic clamp (HEC; P<0.001). Tissue glucose uptake during the HEC of female AS160-KO versus WT rats was: 1) significantly lower in epitrochlearis (P<0.05) and extensor digitorum longus (EDL; P<0.01) muscles of AS160-KO compared to WT rats; 2) not different in soleus, gastrocnemius or WAT; and 3) ~3-fold greater in the heart (P<0.05). GLUT4 protein content was reduced in AS160-KO versus WT rats in the epitrochlearis (P<0.05), EDL (P<0.05), gastrocnemius (P<0.05), soleus (P<0.05), WAT (P<0.05), and the heart (P<0.005). Insulin-stimulated glucose uptake by isolated epitrochlearis and soleus muscles was lower (P<0.001) in AS160-KO versus WT rats. Akt phosphorylation of insulin-stimulated tissues was not different between the genotypes. A secondary objective was to probe processes that might account for the genotype-related increase in myocardial glucose uptake, including glucose transporter protein abundance (GLUT1, GLUT4, GLUT8, SGLT1), hexokinase II protein abundance, and stimulation of the AMP-activated protein kinase (AMPK) pathway. None of these parameters differed between genotypes. Metabolic phenotyping in the current study revealed AS160 deficiency produced a profound glucoregulatory phenotype in female AS160-KO rats that was strikingly similar to the results previously reported in male AS160-KO rats.


Asunto(s)
Proteínas Activadoras de GTPasa/deficiencia , Gluconeogénesis/genética , Glucosa/metabolismo , Resistencia a la Insulina/genética , Músculo Esquelético/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Modelos Animales de Enfermedad , Femenino , Proteínas Activadoras de GTPasa/genética , Técnica de Clampeo de la Glucosa , Prueba de Tolerancia a la Glucosa , Proteínas Facilitadoras del Transporte de la Glucosa/metabolismo , Humanos , Hígado/metabolismo , Condicionamiento Físico Animal , Ratas , Ratas Transgénicas , Ratas Wistar , Transducción de Señal
20.
J Dairy Sci ; 103(4): 3730-3744, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32008771

RESUMEN

The transition from late gestation to early lactation is associated with extensive changes in metabolic, endocrine, and immune functions in dairy cows. Skeletal muscle plays an important role in maintaining the homeorhetic adaptation to the metabolic needs of lactation. The objective of this study was to characterize the skeletal muscle metabolome in the context of the metabolic changes that occur during the transition period in dairy cows with high (HBCS) versus normal body condition (NBCS). Fifteen weeks antepartum, 38 pregnant multiparous Holstein cows were assigned to 1 of 2 groups, which were fed differently to reach the targeted BCS and back fat thickness (BFT) until dry-off at -49 d before calving (HBCS: >3.75 and >1.4 cm; NBCS: <3.5 and <1.2 cm). During the dry period and the subsequent lactation, both groups were fed identical diets. The differences in both BCS and BFT were maintained throughout the study. The metabolome was characterized in skeletal muscle samples (semitendinosus muscle) collected on d -49, 3, 21, and 84 relative to calving using a targeted metabolomics approach (AbsoluteIDQ p180 kit; Biocrates Life Sciences AG, Innsbruck, Austria), which allowed for the quantification of up to 188 metabolites from 6 different compound classes (acylcarnitines, amino acids, biogenic amines, glycerophospholipids, sphingolipids, and hexoses). On d -49, the concentrations of citrulline and hydroxytetradecadienyl-l-carnitine in muscle were higher in HBCS cows than in NBCS cows, but those of carnosine were lower. Over-conditioning did not affect the muscle concentrations of any of the metabolites on d 3. On d 21, the concentrations of phenylethylamine and linoleylcarnitine in muscle were lower in HBCS cows than in NBCS cows, and the opposite was true for lysophosphatidylcholine acyl C20:4. On d 84, the significantly changed metabolites were mainly long-chain (>C32) acyl-alkyl phosphatidylcholine and di-acyl phosphatidylcholine, along with 3 long-chain (>C16) sphingomyelin that were all lower in HBCS cows than in NBCS cows. These data contribute to a better understanding of the metabolic adaptation in skeletal muscle of dairy cows during the transition period, although the physiological significance and underlying molecular mechanisms responsible for the regulation of citrulline, hydroxytetradecadienyl-l-carnitine, carnosine, and phenylethylamine associated with over-conditioning are still elusive and warrant further investigation. The changes observed in muscle lysophosphatidylcholine and phosphatidylcholine concentrations may point to an alteration in phosphatidylcholine metabolism, probably resulting in an increase in membrane stiffness, which may lead to abnormalities in insulin signaling in the muscle of over-conditioned cows.


Asunto(s)
Lactancia/fisiología , Metaboloma , Músculo Esquelético/metabolismo , Periodo Posparto/metabolismo , Animales , Bovinos , Dieta/veterinaria , Metabolismo Energético/fisiología , Femenino , Insulina/metabolismo , Metabolismo de los Lípidos , Embarazo
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