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1.
Ecotoxicol Environ Saf ; 188: 109876, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31704319

RESUMO

This study aimed to assess the levels of pyrethroids and organochlorine residues in the tissues of cultured Mugil capito and in water samples obtained from three different sites (Al-Hamol, Al-Riad and Sidi Salem; referred to as Area 1, Area 2, and Area 3, respectively) in the Delta region, Egypt. The study also assessed the biochemical markers in exposed mullet and evaluated the impact of these residues on the expression of insulin-like growth factor 1 (IGF-1) in muscle and cytochrome P4501A (CYP1A) in liver tissues using qRT-PCR and SDS-PAGE methods. The results revealed that pesticide residue levels in the water were variable, but were lower than detected levels in fish. Significant (P < 0.05) differences were found across the three study areas in terms of serum ALT, but the serum AST level was not significantly (P > 0.05) elevated in all study regions. Serum creatinine and urea levels were significantly (P < 0.05) elevated in area 3. Furthermore, glutathione and malondialdehyde concentrations significantly increased (P < 0.05) in liver tissues in area 3. Using the qRT-PCR technique, the results revealed that the expression level of IGF-1 was most significant in area 3, while the expression level of CYP1A was most significant in area 1. The protein profile showed some differences in band numbers and molecular weights of protein bands across different regions. Overall, the alteration in biochemical parameters revealed pesticide interference with the metabolic processes of fish. Furthermore, the pesticide pollution had an effect on the expression of IGF-1 and CYP1A genes and led to changes in the protein profile. Therefore, these markers can be used to monitor fish distress following exposure to the pollutant.


Assuntos
Família 1 do Citocromo P450/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Hidrocarbonetos Clorados/toxicidade , Fator de Crescimento Insulin-Like I/genética , Proteínas Musculares/metabolismo , Piretrinas/toxicidade , Smegmamorpha/metabolismo , Animais , Aquicultura , Egito , Biomarcadores Ambientais/genética , Hidrocarbonetos Clorados/análise , Hidrocarbonetos Clorados/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Proteínas Musculares/química , Resíduos de Praguicidas/análise , Resíduos de Praguicidas/metabolismo , Resíduos de Praguicidas/toxicidade , Piretrinas/análise , Piretrinas/metabolismo , Alimentos Marinhos/análise , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/metabolismo
2.
Food Chem ; 309: 125614, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-31678672

RESUMO

Effects of partial substitution of NaCl with KCl, MgCl2 or CaCl2 on oxidative characteristics of myofibrillar protein (MP) in a hydroxyl radical generating system and their heat-induced gel properties were investigated. Results indicated that MP oxidation is dependent upon the different chloride salt types and substitution degree. MP at 0.60 M NaCl was beneficial to protein unfolding and gel quality in the oxidative system. Increased formation of disulfide bonds affected the MP conformation and resulted in a large particle size and an aggregatednetworkofgel at the 50% substitution degree of KCl. The presence of CaCl2 or MgCl2 substitutes contributed to protein polymerization and insolubility. MP aggregation restrained the formation of dense and continuous gel networks during heating, and thus resulted in a low-grade gel. Ca2+ had more serious impact on gel properties than Mg2+, dependent on different cation effects. Substitution of 25% NaCl by KCl gave acceptable gel quality in MP.


Assuntos
Manipulação de Alimentos/métodos , Proteínas Musculares/química , Cloreto de Potássio/química , Cloreto de Sódio/química , Animais , Cloreto de Cálcio/química , Dissulfetos/química , Géis/química , Radical Hidroxila/química , Cloreto de Magnésio/química , Oxirredução , Tamanho da Partícula , Desdobramento de Proteína
3.
Food Chem ; 308: 125576, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-31648092

RESUMO

This study investigated the effects of cold storage at different temperatures (4, -0.5, -3, and -20 °C) on protein degradation and its relationship to structural changes of black carp muscle. At -0.5 and 4 °C, major structural changes occurred, including the formation of gaps between myofibers and myofibrils, breakage of myofibrils and myofibers, and degradation of sarcoplasmic reticulum. Gel-based proteomic analysis showed that these structural changes were accompanied by degradation of a series of myofibrillar proteins, including titin, nebulin, troponin, myosin, myomesin, myosin-binding protein, and α-actinin. Loss of extractable gelatinolytic and caseinolytic protease activities was also observed. At -3 and -20 °C, formation of ice crystals was the most noticeable change. The major proteins were degraded at different locations in the black carp muscle, and gelatinolytic and caseinolytic proteases appear to contribute to the degradation of those proteins.


Assuntos
Carpas/metabolismo , Actinina/metabolismo , Animais , Proteínas de Transporte , Temperatura Baixa , Conectina/metabolismo , Cyprinidae/metabolismo , Proteínas Musculares/metabolismo , Miofibrilas/metabolismo , Miosinas/metabolismo , Proteólise , Proteômica
4.
J Sci Food Agric ; 100(1): 119-128, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31441054

RESUMO

BACKGROUND: T-2 toxin (T-2) is a potent mycotoxin and a common contaminant of aquatic animal feed, posing a serious risk to health and aquatic animals. We investigated the effect of T-2 on shrimp muscle proteins using proteomics and conventional biochemical methods. Shrimp were fed a diet containing T-2 at 0-12.2 mg kg-1 for 20 days, and changes to the muscle protein composition, ATPase activities, and the sulfhydryl (SH) content and hydrophobicity of actomyosin (AM) were determined. A proteomics study of the proteins was conducted with sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), two-dimensional (2D) electrophoresis, and matrix-assisted laser desorption/ionization - time of flight mass spectrometry (MALDI-TOF/TOF MS). RESULTS: Exposure to T-2 markedly affected the muscle protein composition of shrimp in a concentration-responsive manner that displayed a diphasic effect. At a low T-2 concentration (1.2 mg kg-1 ), the levels of three major muscle proteins (myofibrillar, sarcoplasmic, and stroma) increased but at higher concentrations they declined progressively. T-2 exposure also led to a breakdown of muscle proteins as evidenced by increases in alkali-soluble protein and the surface hydrophobicity (SoANS) of AM. Thirty differentially expressed proteins were detected, 12 of which showed a concentration-response relationship with T-2 exposure. Among them, 11 homologous proteins were identified by mass spectrometry (MS), with several being key enzymes in energy metabolism. CONCLUSION: This study demonstrated that T-2 exposure at medium to high concentrations could significantly affect the protein composition and quality of shrimp muscle, and potentially some of its key metabolisms. One of the arginine kinases (spot 27) was particularly responsive to T-2 and could potentially be used as a biomarker protein for T-2 intoxication by shrimp. © 2019 Society of Chemical Industry.


Assuntos
Proteínas Musculares/química , Penaeidae/efeitos dos fármacos , Frutos do Mar/análise , Toxina T-2/toxicidade , Ração Animal/análise , Animais , Eletroforese em Gel de Poliacrilamida , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Músculos/química , Músculos/efeitos dos fármacos , Músculos/metabolismo , Penaeidae/química , Penaeidae/genética , Penaeidae/metabolismo , Proteômica , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
5.
J Sci Food Agric ; 100(1): 258-267, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31512250

RESUMO

BACKGROUND: Composite gels were individually prepared from 20 g kg-1 myofibrillar protein (MP) imbedded with typical native starch (potato, tapioca, rice or corn starch) in 0.6 mol L-1 NaCl at pH 6.2. The gel strength, water holding capacity, rheological properties and microstructure of the obtained myofibrillar protein-starch composite gels were evaluated. RESULTS: Tapioca starch improved (P < 0.05) gel strength and water holding capacity of MP composite gel at 80 °C. Rheological properties of MP-starch composites differed significantly with the addition of different types of native starch. Additionally, the promoting effect of starch on the storage modulus of the composite gels positively correlated with the gelatinization properties of different typical starch. Environmental scanning electron microscopy showed that the filling effect of starch on the composite gel was related to the pasting temperature and particle size of typical starch, with almost no particles forming at 80 °C. Moreover, the addition of starch changed the relaxation peak area and increased the relaxation time in nuclear magnetic resonance tests, which suggested that starch could improve the water holding capacity of MP-starch composite gels. CONCLUSION: Different typical native starch has varied impacts on the gel strength, water holding capacity, rheological properties and microstructure of MP gels, indicating the potential and feasibility of these typical native starches as an addition agent to modify the textural properties in comminuted meat products. © 2019 Society of Chemical Industry.


Assuntos
Produtos da Carne/análise , Proteínas Musculares/química , Miofibrilas/química , Extratos Vegetais/química , Amido/química , Animais , Aditivos Alimentares/química , Géis/química , Espectroscopia de Ressonância Magnética , Manihot/química , Oryza/química , Reologia , Solanum tuberosum/química , Suínos , Zea mays/química
6.
J Sci Food Agric ; 100(2): 551-559, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31587285

RESUMO

BACKGROUND: Phosphorylation is one of the most important post-translational modifications. Currently, many postmortem protein phosphorylation studies in muscle have been related to meat quality such as tenderness and color stability. However, the effects of various storage temperatures (25, 15, 4 and -1.5 °C) on the phosphorylation level of protein are poorly understood. Changes in the protein phosphorylation levels in postmortem ovine muscle at various storage temperatures were determined in this study. RESULTS: The obtained data showed that pH decline rate was significantly inhibited at -1.5 °C from 12 h to 7 days postmortem (P < 0.05). The ATP consumption rate was higher at 25 °C than that at other three temperatures (P < 0.05). Analysis of the temperature, pH and ATP content revealed that the ATP content was related to the phosphorylation levels of individual protein bands. Phosphorylated myofibrillar and sarcoplasmic proteins, such as myosin binding protein C, troponin T3, myosin light chain 1, glucose-6-phosphate isomerase and pyruvate kinase, were mainly involved in glycolysis and muscle contraction. CONCLUSION: The global and specific protein phosphorylation levels can be influenced by the postmortem storage temperature of muscle. Phosphorylation of proteins was correlated with glycolysis and muscle contraction. Certain phosphorylated proteins, such as heat shock proteins, require further study to clarify their effects on meat traits. © 2019 Society of Chemical Industry.


Assuntos
Armazenamento de Alimentos/métodos , Carne/análise , Proteínas Musculares/química , Músculo Esquelético/química , Animais , Armazenamento de Alimentos/instrumentação , Glicólise , Fosforilação , Mudanças Depois da Morte , Ovinos , Temperatura Ambiente
7.
Artigo em Inglês | MEDLINE | ID: mdl-31465878

RESUMO

This study was conducted to characterise the muscle-specific gene expression, energy metabolism level and growth rates of Atlantic salmon Salmo salar L. reared under different photoperiod regimes. The effects of two photoperiod regimes - LD 16:8 (16 h light:8 h dark) and LD 24:0 (24 h light:0 h dark) over a period of 3 months (August to October) on growth, energy metabolism enzyme activities (cytochrome c oxidase, COX; lactate dehydrogenase, LDH; and aldolase) and the gene expression levels of myogenic regulatory factors (MRFs - MyoD1 paralogues (MyoD1a, MyoD1b, MyoD1c), Myf5, MyoG), myostatin paralogues (MSTN-1a, MSTN-1b, MSTN-2a) and the fast skeletal myosin heavy chain (MyHC) in the muscles of Atlantic salmon underyearling fry (0+) were investigated. The experiment was conducted in a fish hatchery with natural variations in water temperature. The results were compared with those obtained in salmon reared under the lighting conditions of a fish hatchery (HL, hatchery lighting). The results revealed that the fry reared under constant light (LD 24:0) grew faster and were bigger at the end of the experiment. Fishes reared within the photoperiod regime LD 16:8 had a lower growth rate. COX activity was lower in fish under the LD 16:8 regime compared with the LD 24:0 group. The LDH and aldolase enzyme activities were higher in the group with constant light in comparison to control in the beginning of September. The expression level for all of the genes studied variated during the duration of the experiment, and MyHC, MyoG, MyoD1a and Myf5 expression depended on the light regime as well. The more noticeable changes in gene expression occurred in October. The MyHC and MyoG mRNA levels increased, accompanied by MyD1c gene expression, in both groups that had additional lighting (LD 16:8 and LD24:0) at the beginning of October and were higher than the HL group. In the HL group, the elevation of MyHC and MyoG mRNA was gradual during October, but there was a sharp increase in Myf5 expression at the beginning of October. MyoD1 paralogues differently expressed during the experiment. The MyoD1a mRNA level was elevated at the end of October along with MyHC and MyoG expression, but MyoD1b and MyoD1c mRNA levels decreased along with Myf5 gene expression. The expression of MSTN paralogues were elevated with increases in MyHC and MRFs transcripts. These findings show that constant light has a positive effect on the growth rate of salmon, affecting the aerobic and anaerobic capacity in their muscles. The alterations in muscle-specific gene expression between the groups with different light indicated that the mechanisms for regulating muscle growth processes in fish depend on photoperiod duration.


Assuntos
Proteínas de Peixes/biossíntese , Regulação Enzimológica da Expressão Gênica/fisiologia , Proteínas Musculares/biossíntese , Músculo Esquelético/enzimologia , Salmo salar/metabolismo , Animais
8.
BMC Complement Altern Med ; 19(1): 360, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31829159

RESUMO

BACKGROUND: Lingguizhugan decoction (LGZG), an ancient Chinese herbal formula, has been used to treat cardiovascular diseases in eastern Asia. We investigated whether LGZG has protective activity and the mechanism underlying its effect in an animal model of heart failure (HF). METHODS: A rat model of HF was established by administering eight intraperitoneal injections of doxorubicin (DOX) (cumulative dose of 16 mg/kg) over a 4-week period. Subsequently, LGZG at 5, 10, and 15 mL/kg/d was administered to the rats intragastrically once daily for 4 weeks. The body weight, heart weight index (HWI), heart weight/tibia length ratio (HW/TL), and serum BNP level were investigated to assess the effect of LGZG on HF. Echocardiography was performed to investigate cardiac function, and H&E staining to visualize myocardial morphology. Myocardial ultrastructure and T-tubule-sarcoplasmic reticulum (TT-SR) junctions were observed by transmission electron microscopy. The JP-2 protein level was determined by Western blotting. The mRNA level of CACNA1S and RyR2 and the microRNA-24 (miR-24) level were assayed by quantitative RT-PCR. RESULTS: Four weeks after DOX treatment, rats developed cardiac damage and exhibited a significantly increased BNP level compared with the control rats (169.6 ± 29.6 pg/mL versus 80.1 ± 9.8 pg/mL, P < 0.001). Conversely, LGZG, especially at the highest dose, markedly reduced the BNP level (93.8 ± 17.9 pg/mL, P < 0.001). Rats treated with DOX developed cardiac dysfunction, characterized by a strong decrease in left ventricular ejection fraction compared with the control (58.5 ± 8.7% versus 88.7 ± 4.0%; P < 0.001). Digoxin and LGZG improved cardiac dysfunction (79.6 ± 6.1%, 69.2 ± 2.5%, respectively) and preserved the left ventricular ejection fraction (77.9 ± 5.1, and 80.5 ± 4.9, respectively, P < 0.01). LGZG also improved the LVEDD, LVESD, and FS and eliminated ventricular hypertrophy, as indicated by decreased HWI and HW/TL ratio. LGZG attenuated morphological abnormalities and mitochondrial damage in the myocardium. In addition, a high dose of LGZG significantly downregulated the expression of miR-24 compared with that in DOX-treated rats (fold change 1.4 versus 3.4, P < 0.001), but upregulated the expression of JP-2 and antagonized DOX-induced T-tubule TT-SR microstructural remodeling. These activities improved periodic Ca2+ transients and cell contraction, which may underly the beneficial effect of LGZG on HF. CONCLUSIONS: LGZG exerted beneficial effects on DOX-induced HF in rats, which were mediated in part by improved TT-SR microstructural remodeling.


Assuntos
Cardiotônicos/farmacologia , Doxorrubicina/efeitos adversos , Insuficiência Cardíaca/induzido quimicamente , Extratos Vegetais/farmacologia , Retículo Sarcoplasmático/efeitos dos fármacos , Animais , Coração/efeitos dos fármacos , Masculino , Proteínas de Membrana/metabolismo , MicroRNAs , Proteínas Musculares/metabolismo , Miocárdio/química , Miocárdio/metabolismo , Ratos , Ratos Sprague-Dawley , Retículo Sarcoplasmático/ultraestrutura
9.
Yi Chuan ; 41(12): 1110-1118, 2019 Dec 20.
Artigo em Chinês | MEDLINE | ID: mdl-31857282

RESUMO

Myogenesis is a complex physiological process that is mainly involved in the proliferation of myogenic stem cells to form myoblasts, which then differentiated and fused to form multinucleated myotubes. Many proteins have been found to be involved in myoblast fusion, but none of them are muscle-specific fusion proteins. In recent years, two muscle-specific transmembrane proteins, i.e. Myomaker and Myomerger, have been discovered and identified, which can coordinate and promote the fusion of myoblasts and thus participate in the process of myogenesis. In this review, we summarize the research progress of Myomaker and Myomerger in myogenesis, including their expression patterns and functional domains, as well as their participation in myoblast fusion mechanisms, aiming to provide relevant ideas for in-depth study of the myogenesis process and treatment of diseases related to myoblast fusion.


Assuntos
Proteínas de Membrana , Músculo Esquelético , Mioblastos , Animais , Diferenciação Celular , Fusão Celular , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Desenvolvimento Muscular , Proteínas Musculares , Músculo Esquelético/citologia , Mioblastos/citologia
10.
Zhonghua Zhong Liu Za Zhi ; 41(12): 918-922, 2019 Dec 23.
Artigo em Chinês | MEDLINE | ID: mdl-31874549

RESUMO

Objective: To investigate the expression level of antisense transcript of pseudogene, general transcription factor Ⅱi psedugen23 (GTF2IP23), in breast cancer and its effect on the host gene general transcription factor Ⅱi (GTF2I). Methods: The expressions of GTF2IP23 and GTF2I were detected in 40 cases of invasive breast cancer tumors and their counterparts by using quantitative real-time polymerase chain reaction (qRT-PCR). The effects of GTF2IP23 on the expression of GTF2I gene and cell proliferation and migration were analyzed by overexpression of GTF2IP23 in breast cancer cells. Results: The expression of GTF2IP23 mRNA in breast cancer tissues was significantly higher than that in adjacent tissues (P<0.001), while the expression of GTF2I mRNA was significantly lower than that in adjacent tissues (P=0.007). The expression of GTF2IP23 was negatively correlated with GTF2I (r=-0.335, P=0.025). The expression of GTF2IP23 in breast cancer cells was significantly higher than in normal breast cells (P<0.01), while GTF2I expression in breast cancer cells was significantly lower than that in normal breast cells (P<0.01). Overexpression of GTF2IP23 in ZR-75-30 cells significantly reduced the expression of GTF2I (P=0.034) and enhanced cell proliferation (P=0.017) and migration (P=0.026) capacity. Conclusions: GTF2IP23 is distinctly upregulated in breast cancer, it inhibits the expression of real gene GTF2I and promotes the proliferation of breast cancer cells.


Assuntos
Neoplasias da Mama/sangue , Proteínas Musculares/metabolismo , Proteínas Nucleares/metabolismo , Transativadores/metabolismo , Fatores de Transcrição TFII/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas Musculares/genética , Proteínas Nucleares/genética , Reação em Cadeia da Polimerase em Tempo Real , Transativadores/genética , Fatores de Transcrição TFII/metabolismo
11.
Nat Commun ; 10(1): 4679, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31616000

RESUMO

Postsynaptic density (PSD) proteins have been implicated in the pathophysiology of neurodevelopmental and psychiatric disorders. Here, we present detailed clinical and genetic data for 20 patients with likely gene-disrupting mutations in TANC2-whose protein product interacts with multiple PSD proteins. Pediatric patients with disruptive mutations present with autism, intellectual disability, and delayed language and motor development. In addition to a variable degree of epilepsy and facial dysmorphism, we observe a pattern of more complex psychiatric dysfunction or behavioral problems in adult probands or carrier parents. Although this observation requires replication to establish statistical significance, it also suggests that mutations in this gene are associated with a variety of neuropsychiatric disorders consistent with its postsynaptic function. We find that TANC2 is expressed broadly in the human developing brain, especially in excitatory neurons and glial cells, but shows a more restricted pattern in Drosophila glial cells where its disruption affects behavioral outcomes.


Assuntos
Transtornos Mentais/genética , Proteínas do Tecido Nervoso/metabolismo , Transtornos do Neurodesenvolvimento/genética , Proteínas/genética , Adolescente , Adulto , Animais , Transtorno Autístico/genética , Transtorno Autístico/psicologia , Comportamento Animal , Encéfalo/metabolismo , Criança , Pré-Escolar , Anormalidades Craniofaciais/genética , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/psicologia , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster , Epilepsia/genética , Feminino , Humanos , Deficiência Intelectual/genética , Deficiência Intelectual/psicologia , Transtornos do Desenvolvimento da Linguagem/genética , Transtornos do Desenvolvimento da Linguagem/psicologia , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Transtornos Mentais/psicologia , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Mutação , Transtornos do Neurodesenvolvimento/psicologia , Neuroglia/metabolismo , Neurônios/metabolismo , Proteínas/metabolismo , Sequenciamento Completo do Exoma , Adulto Jovem
12.
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
13.
Nature ; 574(7777): 259-263, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31554973

RESUMO

Chikungunya virus (CHIKV) is a re-emerging alphavirus that is transmitted to humans by mosquito bites and causes musculoskeletal and joint pain1,2. Despite intensive investigations, the human cellular factors that are critical for CHIKV infection remain unknown, hampering the understanding of viral pathogenesis and the development of anti-CHIKV therapies. Here we identified the four-and-a-half LIM domain protein 1 (FHL1)3 as a host factor that is required for CHIKV permissiveness and pathogenesis in humans and mice. Ablation of FHL1 expression results in the inhibition of infection by several CHIKV strains and o'nyong-nyong virus, but not by other alphaviruses and flaviviruses. Conversely, expression of FHL1 promotes CHIKV infection in cells that do not normally express it. FHL1 interacts directly with the hypervariable domain of the nsP3 protein of CHIKV and is essential for the replication of viral RNA. FHL1 is highly expressed in CHIKV-target cells and is particularly abundant in muscles3,4. Dermal fibroblasts and muscle cells derived from patients with Emery-Dreifuss muscular dystrophy that lack functional FHL15 are resistant to CHIKV infection. Furthermore,  CHIKV infection  is undetectable in Fhl1-knockout mice. Overall, this study shows that FHL1 is a key factor expressed by the host that enables CHIKV infection and identifies the interaction between nsP3 and FHL1 as a promising target for the development of anti-CHIKV therapies.


Assuntos
Febre de Chikungunya/virologia , Vírus Chikungunya/patogenicidade , Fatores Celulares Derivados do Hospedeiro/metabolismo , Interações Hospedeiro-Patógeno , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas com Domínio LIM/metabolismo , Proteínas Musculares/metabolismo , Animais , Células Cultivadas , Febre de Chikungunya/tratamento farmacológico , Vírus Chikungunya/efeitos dos fármacos , Vírus Chikungunya/genética , Vírus Chikungunya/crescimento & desenvolvimento , Feminino , Fibroblastos/virologia , Células HEK293 , Fatores Celulares Derivados do Hospedeiro/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/deficiência , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas com Domínio LIM/deficiência , Proteínas com Domínio LIM/genética , Masculino , Camundongos , Proteínas Musculares/deficiência , Proteínas Musculares/genética , Mioblastos/virologia , Vírus O'nyong-nyong/crescimento & desenvolvimento , Vírus O'nyong-nyong/patogenicidade , Ligação Proteica , RNA Viral/biossíntese , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo , Replicação Viral
14.
Einstein (Sao Paulo) ; 17(3): eRB4898, 2019 Sep 05.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31508659

RESUMO

Alongside a proper diet, ergogenic aids with potential direct and/or indirect physical performance enhancing effects are sought after for improved adaptation to physical training. Nutritional ergogenics include diet composition changes and/or dietary supplementation. Branched-chain amino acids valine, leucine and isoleucine are widely popular among products with ergogenic claims. Their major marketing appeal derives from allegations that branched-chain amino acids intake combined with resistance physical exercise stimulates muscle protein synthesis. Evidence supporting the efficacy of branched-chain amino acids alone for muscle hypertrophy in humans is somewhat equivocal. This brief review describes physiological and biochemical mechanisms underpinning the effects of complete protein source and branched-chain amino acid intake on skeletal muscle growth in the postabsorptive and post-exercise state. Evidence in favor of or against potential anabolic effects of isolated branched-chain amino acid intake on muscle protein synthesis in humans is also examined.


Assuntos
Aminoácidos de Cadeia Ramificada/metabolismo , Proteínas Musculares/biossíntese , Aminoácidos de Cadeia Ramificada/fisiologia , Suplementos Nutricionais , Exercício/fisiologia , Absorção Gastrointestinal/efeitos dos fármacos , Humanos , Músculo Esquelético/metabolismo , Período Pós-Prandial/efeitos dos fármacos
15.
Elife ; 82019 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-31549961

RESUMO

Neuromuscular junction is a synapse between motoneurons and skeletal muscles, where acetylcholine receptors (AChRs) are concentrated to control muscle contraction. Studies of this synapse have contributed to our understanding of synapse assembly and pathological mechanisms of neuromuscular disorders. Nevertheless, underlying mechanisms of NMJ formation was not well understood. To this end, we took a novel approach - studying mutant genes implicated in congenital myasthenic syndrome (CMS). We showed that knock-in mice carrying N88K, a prevalent CMS mutation of Rapsyn (Rapsn), died soon after birth with profound NMJ deficits. Rapsn is an adapter protein that bridges AChRs to the cytoskeleton and possesses E3 ligase activity. In investigating how N88K impairs the NMJ, we uncovered a novel signaling pathway by which Agrin-LRP4-MuSK induces tyrosine phosphorylation of Rapsn, which is required for its self-association and E3 ligase activity. Our results also provide insight into pathological mechanisms of CMS.


Assuntos
Agrina/metabolismo , Proteínas Musculares/metabolismo , Proteínas Mutantes/metabolismo , Mutação de Sentido Incorreto , Síndromes Miastênicas Congênitas/fisiopatologia , Transdução de Sinais , Animais , Modelos Animais de Doenças , Técnicas de Introdução de Genes , Camundongos , Proteínas Musculares/genética , Proteínas Mutantes/genética
16.
Molecules ; 24(18)2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31500282

RESUMO

The present study investigated the antioxidant potential and the ability to inhibit lipid and protein oxidation in bovine meat of four native Chilean species: canelo (Drimys winteri), nalca (Gunnera tinctoria), tiaca (Caldcluvia paniculata), and ulmo (Eucryphia cordifolia). Phenolic acids (gallic, chlorogenic, caffeic, and coumaric) and flavonoids (catechin, epicatechin, and rutin) were identified and quantified by HPLC-MS/MS. Drimys winteri extract exhibited the highest antioxidant capacity evaluated by oxygen radical absorption capacity-red pyrogallol method (ORAC-PGR) and ferric ion reducing antioxidant power (FRAP) assays. All extracts decreased lipid oxidation induced by 2,2'-azo-bis(2-amidinopropane) dihydrochloride (AAPH) derived peroxyl radicals by anywhere between 30% and 50% the. In addition, canelo and nalca extracts decreased spontaneous oxidation by around 57% and 37% in relation to the control group, being even more efficient than butylated hydroxyanisole (BHT) a synthetic antioxidant. Protein oxidation in the myofibrillar proteins was evaluated by the formation of protein carbonyls and loss of protein thiols. The canelo, ulmo, and nalca extracts decreased the formation of carbonyls by around 30%. Plant extracts and BHT did not show an antioxidant effect on protein thiol loss. However, tiaca and ulmo extracts exerted a pro-oxidant effect, favoring the oxidation of sulfhydryl groups. The oxidizing system induced structural changes in myofibrillar protein (SDS-PAGE). A protective effect on protein structure from the canelo extract can be observed during the incubation when compared to samples incubated with AAPH.


Assuntos
Antioxidantes/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Magnoliopsida/química , Proteínas Musculares/química , Animais , Antioxidantes/química , Bovinos , Flavonoides/química , Flavonoides/farmacologia , Hidroxibenzoatos/química , Hidroxibenzoatos/farmacologia , Componentes Aéreos da Planta/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química
17.
Braz J Med Biol Res ; 52(9): e8551, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31482977

RESUMO

Fibroblasts are a highly heterogeneous population of cells, being found in a large number of different tissues. These cells produce the extracellular matrix, which is essential to preserve structural integrity of connective tissues. Fibroblasts are frequently engaged in migration and remodeling, exerting traction forces in the extracellular matrix, which is crucial for matrix deposition and wound healing. In addition, previous studies performed on primary myoblasts suggest that the E3 ligase MuRF2 might function as a cytoskeleton adaptor. Here, we hypothesized that MuRF2 also plays a functional role in skeletal muscle fibroblasts. We found that skeletal muscle fibroblasts express MuRF2 and its siRNA knock-down promoted decreased fibroblast migration, cell border accumulation of polymerized actin, and down-regulation of the phospho-Akt expression. Our results indicated that MuRF2 was necessary to maintain the actin cytoskeleton functionality in skeletal muscle fibroblasts via Akt activity and exerted an important role in extracellular matrix remodeling in the skeletal muscle tissue.


Assuntos
Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Fibroblastos/fisiologia , Proteínas Musculares/fisiologia , Músculo Esquelético/fisiologia , Ubiquitina-Proteína Ligases/fisiologia , Animais , Western Blotting , Fibroblastos/metabolismo , Imunofluorescência , Camundongos , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
18.
Biol Pharm Bull ; 42(9): 1437-1445, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474705

RESUMO

Chronic kidney disease (CKD), a chronic catabolic condition, is characterized by muscle wasting and decreased muscle endurance. Many insights into the molecular mechanisms of muscle wasting in CKD have been obtained. A persistent imbalance between protein degradation and synthesis in muscle causes muscle wasting. During muscle wasting, high levels of reactive oxygen species (ROS) and inflammatory cytokines are detected in muscle. These increased ROS and inflammatory cytokine levels induce the expression of myostatin. The myostatin binding to its receptor activin A receptor type IIB stimulates the expression of atrogenes such as atrogin-1 and muscle ring factor 1, members of the muscle-specific ubiquitin ligase family. Impaired mitochondrial function also contributes to reducing muscle endurance. The increased protein-bound uremic toxin, parathyroid hormone, glucocorticoid, and angiotensin II levels that are observed in CKD all have a negative effect on muscle mass and endurance. Among the protein-bound uremic toxins, indoxyl sulfate, an indole-containing compound has the potential to induce muscle atrophy by stimulating ROS-mediated myostatin and atrogenes expression. Indoxyl sulfate also impairs mitochondrial function. Some potential therapeutic approaches based on the muscle wasting mechanisms in CKD are currently in the testing stages.


Assuntos
Proteínas Musculares/biossíntese , Músculo Esquelético/metabolismo , Insuficiência Renal Crônica/complicações , Sarcopenia/etiologia , Citocinas/imunologia , Humanos , Indicã/biossíntese , Músculo Esquelético/imunologia , Miostatina/biossíntese , Estresse Oxidativo/imunologia , Proteólise , Espécies Reativas de Oxigênio/metabolismo , Insuficiência Renal Crônica/imunologia , Insuficiência Renal Crônica/metabolismo , Sarcopenia/imunologia , Sarcopenia/metabolismo
19.
Nutrients ; 11(8)2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31394788

RESUMO

Plant-sourced proteins offer environmental and health benefits, and research increasingly includes them in study formulas. However, plant-based proteins have less of an anabolic effect than animal proteins due to their lower digestibility, lower essential amino acid content (especially leucine), and deficiency in other essential amino acids, such as sulfur amino acids or lysine. Thus, plant amino acids are directed toward oxidation rather than used for muscle protein synthesis. In this review, we evaluate the ability of plant- versus animal-based proteins to help maintain skeletal muscle mass in healthy and especially older people and examine different nutritional strategies for improving the anabolic properties of plant-based proteins. Among these strategies, increasing protein intake has led to a positive acute postprandial muscle protein synthesis response and even positive long-term improvement in lean mass. Increasing the quality of protein intake by improving amino acid composition could also compensate for the lower anabolic potential of plant-based proteins. We evaluated and discussed four nutritional strategies for improving the amino acid composition of plant-based proteins: fortifying plant-based proteins with specific essential amino acids, selective breeding, blending several plant protein sources, and blending plant with animal-based protein sources. These nutritional approaches need to be profoundly examined in older individuals in order to optimize protein intake for this population who require a high-quality food protein intake to mitigate age-related muscle loss.


Assuntos
Anabolizantes , Proteínas na Dieta/administração & dosagem , Proteínas Musculares/administração & dosagem , Músculo Esquelético/fisiologia , Proteínas de Plantas/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Aminoácidos/análise , Animais , Proteínas na Dieta/farmacologia , Digestão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Musculares/análise , Proteínas Musculares/metabolismo , Fenômenos Fisiológicos da Nutrição , Proteínas de Plantas/análise , Proteínas de Plantas/metabolismo , Biossíntese de Proteínas/fisiologia
20.
Cell Prolif ; 52(6): e12673, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31418947

RESUMO

OBJECTIVE: Inflammatory bowel disease (IBD) is a disorder intestinal inflammation and impaired barrier function, associated with increased epithelial expression of monocarboxylate transporter 4 (MCT4). However, the specific non-metabolic function and clinical relevance of MCT4 in IBD remain to be fully elucidated. METHODS: Lentivirus-mediated overexpression of MCT4 was used to assess the role of MCT4 in transcriptionally regulating ZO-1 and IL-6 expression by luciferase assays, WB and ChIP. IP was used to analyse the effect of MCT4 on the interaction NF-κB-CBP or CREB-CBP, and these MCT4-mediated effects were confirmed in vivo assay. RESULTS: We showed that ectopic expression of MCT4 inhibited ZO-1 expression, while increased pro-inflammatory factors expression, leading to destroy intestinal epithelial barrier function in vitro and in vivo. Mechanistically, MCT4 contributed NF-κB p65 nuclear translocation and increased the binding of NF-κB p65 to the promoter of IL-6, which is attributed to MCT4 enhanced NF-κB-CBP interaction and dissolved CREB-CBP complex, resulting in reduction of CREB activity and CREB-mediated ZO-1 expression. In addition, treatment of experimental colitis with MCT4 inhibitor α-cyano-4-hydroxycinnamate (CHC) ameliorated mucosal intestinal barrier function, which was due to attenuation of pro-inflammation factors expression and enhancement of ZO-1 expression. CONCLUSION: These findings suggested a novel role of MCT4 in controlling development of IBD and provided evidence for potential targets of IBD.


Assuntos
Epitélio/efeitos dos fármacos , Interleucina-6/metabolismo , Transportadores de Ácidos Monocarboxílicos/metabolismo , Proteínas Musculares/metabolismo , Proteína da Zônula de Oclusão-1/metabolismo , Células CACO-2 , Colo/metabolismo , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , NF-kappa B/efeitos dos fármacos , NF-kappa B/metabolismo , Fator de Transcrição RelA/farmacologia , Fator de Necrose Tumoral alfa/farmacologia , Proteína da Zônula de Oclusão-1/efeitos dos fármacos
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