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1.
PLoS Genet ; 16(8): e1008966, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32776922

RESUMO

The vacuole of the yeast Saccharomyces cerevisiae plays an important role in nutrient storage. Arginine, in particular, accumulates in the vacuole of nitrogen-replete cells and is mobilized to the cytosol under nitrogen starvation. The arginine import and export systems involved remain poorly characterized, however. Furthermore, how their activity is coordinated by nitrogen remains unknown. Here we characterize Vsb1 as a novel vacuolar membrane protein of the APC (amino acid-polyamine-organocation) transporter superfamily which, in nitrogen-replete cells, is essential to active uptake and storage of arginine into the vacuole. A shift to nitrogen starvation causes apparent inhibition of Vsb1-dependent activity and mobilization of stored vacuolar arginine to the cytosol. We further show that this arginine export involves Ypq2, a vacuolar protein homologous to the human lysosomal cationic amino acid exporter PQLC2 and whose activity is detected only in nitrogen-starved cells. Our study unravels the main arginine import and export systems of the yeast vacuole and suggests that they are inversely regulated by nitrogen.


Assuntos
Arginina/metabolismo , Nitrogênio/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Aminoácidos/genética , Transporte Biológico/genética , Humanos , Membranas Intracelulares/metabolismo , Lisossomos/genética , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Saccharomyces cerevisiae/metabolismo , Vacúolos/genética , Vacúolos/metabolismo
2.
Medicine (Baltimore) ; 99(27): e21068, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629736

RESUMO

BACKGROUND: Alterations in the levels of arginine and its related catabolic products (ie, ornithine, citrulline, and argininosuccinate) in the urea and nitric oxide cycles were reported to play roles in the pathogenesis of major depressive disorder (MDD). The aim of this meta-analysis study is to explore the associations between arginine with its related catabolic products and MDD, and to discuss the possible role of arginine catabolism in the pathoetiology of MDD. METHODS: This study will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The English language literature published in the databases of PubMed, EMBASE, PsycINFO and Web of Science will be systematically searched. Forest plots will be used to estimate the associations between arginine and its related catabolic products with MDD. Subgroup analysis and meta-regression will also be performed to investigate the source of the potential heterogeneity. Sensitivity analysis will be performed to strengthen the results and to investigate whether any single study would have a significant effect on the results of meta-analysis. Publication bias will be tested for using the funnel plot with Begg test and Egger test. The Newcastle-Ottawa Scale will be applied to assess the risk of bias of observational studies. RESULTS: An integrated assessment of arginine with its related catabolic products may contribute to predict the risk of MDD. ETHICS AND DISSEMINATION: The results of associations between arginine with its related catabolic products and MDD will be reported in a peer-reviewed publication. With our findings from this meta-analysis, we hope to provide the most up-to-date evidence for the contributions of arginine and related catabolic products to predict the risk of MDD. SYSTEMATIC REVIEW REGISTRATION: The protocol of current meta-analysis has been registered at the Open Science Framework [Available at: https://doi.org/10.17605/osf.io/7fn59].


Assuntos
Arginina/metabolismo , Transtorno Depressivo Maior/metabolismo , Redes e Vias Metabólicas/fisiologia , Óxido Nítrico/metabolismo , Transtorno Depressivo Maior/fisiopatologia , Humanos , Medição de Risco , Sensibilidade e Especificidade
3.
Nat Commun ; 11(1): 3241, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32591537

RESUMO

Protein arginine deiminase 4 (PAD4) facilitates the post-translational citrullination of the core histones H3 and H4. While the precise epigenetic function of this modification has not been resolved, it has been shown to associate with general chromatin decompaction and compete with arginine methylation. Recently, we found that histones are subjected to methylglyoxal (MGO)-induced glycation on nucleophilic side chains, particularly arginines, under metabolic stress conditions. These non-enzymatic adducts change chromatin architecture and the epigenetic landscape by competing with enzymatic modifications, as well as changing the overall biophysical properties of the fiber. Here, we report that PAD4 antagonizes histone MGO-glycation by protecting the reactive arginine sites, as well as by converting already-glycated arginine residues into citrulline. Moreover, we show that similar to the deglycase DJ-1, PAD4 is overexpressed and histone citrullination is upregulated in breast cancer tumors, suggesting an additional mechanistic link to PAD4's oncogenic properties.


Assuntos
Histonas/metabolismo , Proteína-Arginina Desiminase do Tipo 4/metabolismo , Aldeído Pirúvico/farmacologia , Animais , Arginina/metabolismo , Neoplasias da Mama/enzimologia , Citrulinação , Citrulina/metabolismo , Feminino , Glicosilação , Humanos , Células MCF-7 , Metilação , Camundongos Endogâmicos BALB C , Camundongos Nus , Modelos Biológicos , Nucleossomos/metabolismo
4.
Eur J Protistol ; 74: 125705, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32464434

RESUMO

The ciliate Paramecium tetraurelia has four arginine kinase genes (AK1, AK2, AK3, and AK4). Of these genes, only AK3 has a signal sequence for farnesylation, a post-translational modification that enables anchoring of the modified enzyme to the ciliary membrane. To confirm this modification, AK3 was synthesized using a cell-free protein synthesis system and the peptide masses were analyzed using peptide mass fingerprinting (PMF). The PMF analysis indicated that the C-terminal peptide of AK3 is farnesylated. Thus, AK3 can be farnesylated under physiologically appropriate conditions. To determine the subcellular localization of P. tetraurelia AK3, Western blot analysis was performed using an AK3 polyclonal antibody for the proteins extracted from intact cells and ciliary fractions. When extraction was performed using Triton X-100, AK3 was detected the ciliary fraction. This result suggested that the ciliary fraction contains AK3. In addition, we investigated the role of P. tetraurelia AKs in ciliary movement using the feeding RNA interference method. The swimming velocity of AK1- and AK3-silenced cells was significantly reduced to half the value of that control cells. In summary, P. tetraurelia AK3 is likely to be located in the ciliary membrane and influences swimming velocity, presumably through the phosphoarginine shuttle system present in cilia.


Assuntos
Arginina Quinase/metabolismo , Arginina/análogos & derivados , Paramecium tetraurellia/enzimologia , Arginina/metabolismo , Cílios/enzimologia , Compostos Organofosforados/metabolismo
5.
PLoS One ; 15(4): e0231633, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32353864

RESUMO

Arginine deprivation cancer therapy targets certain types of malignancies with positive result in many studies and clinical trials. NEI-01 was designed as a novel arginine-depleting enzyme comprising an albumin binding domain capable of binding to human serum albumin to lengthen its half-life. In the present work, NEI-01 is shown to bind to serum albumin from various species, including mice, rat and human. Single intraperitoneal administration of NEI-01 to mice reduced plasma arginine to undetectable level for at least 9 days. Treatment of NEI-01 specifically inhibited cell viability of MIA PaCa-2 and PANC-1 cancer cell lines, which were ASS1 negative. Using a human pancreatic mouse xenograft model, NEI-01 treatment significantly reduced tumor volume and weight. Our data provides proof of principle for a cancer treatment strategy using NEI-01.


Assuntos
Antineoplásicos/uso terapêutico , Arginina/metabolismo , Carcinoma/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Desiminases de Arginina em Proteínas/uso terapêutico , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/metabolismo , Arginina/sangue , Arginina/deficiência , Argininossuccinato Sintase/metabolismo , Linhagem Celular Tumoral , Feminino , Humanos , Injeções Intraperitoneais , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Ligação Proteica , Desiminases de Arginina em Proteínas/administração & dosagem , Desiminases de Arginina em Proteínas/metabolismo , Ratos , Albumina Sérica/metabolismo
6.
J Anim Sci ; 98(6)2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32415842

RESUMO

This study determined whether extracellular citrulline is degraded by ruminal bacteria of sheep. In the first experiment, whole rumen fluid (3 mL) from six adult Suffolk sheep was incubated at 37 °C with 5 mM l-glutamine (Gln), l-glutamate (Glu), l-arginine (Arg), or l-citrulline (Cit) for 0, 0.5, 1, and 2 h or with 0, 0.5, 2, or 5 mM Gln, Glu, Arg, or Cit for 2 h. An aliquot (50 µL) of the incubation solution was collected at the predetermined time points for amino acids (AA) analyses. Results showed extensive hydrolysis of Gln into Glu and ammonia, of Arg into l-ornithine and l-proline, but little or no degradation of extracellular Cit or Glu by ruminal microbes. In the second experiment, six adult Suffolk sheep were individually fed each of three separate supplements (8 g Gln , Cit, or urea) on three separate days along with regular feed (800 g/animal). Blood (2 mL) was sampled from the jugular vein prior to feeding (time 0) and at 0.5, 1, 2, and 4 h after consuming the supplement. Plasma was analyzed for AA, glucose, ammonia, and urea. The concentrations of Cit in the plasma of sheep consuming this AA increased (P < 0.001) by 117% at 4 h and those of Arg increased by 23% at 4 h, compared with the baseline values. Urea or Gln feeding did not affect (P > 0.05) the concentrations of Cit or Arg in plasma. These results indicate that Cit is not metabolized by ruminal microbes of sheep and is, therefore, absorbed as such by the small intestine and used for the synthesis of Arg by extrahepatic tissues.


Assuntos
Bactérias/metabolismo , Citrulina/metabolismo , Rúmen/microbiologia , Ovinos/microbiologia , Amônia/metabolismo , Ração Animal/análise , Animais , Arginina/metabolismo , Dieta/veterinária , Suplementos Nutricionais , Feminino , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Ornitina/sangue , Prolina/metabolismo , Ureia
7.
Nat Commun ; 11(1): 2396, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32409666

RESUMO

Protein arginine methyltransferases (PRMTs) regulate diverse biological processes and are increasingly being recognized for their potential as drug targets. Here we report the discovery of a potent, selective, and cell-active chemical probe for PRMT7. SGC3027 is a cell permeable prodrug, which in cells is converted to SGC8158, a potent, SAM-competitive PRMT7 inhibitor. Inhibition or knockout of cellular PRMT7 results in drastically reduced levels of arginine monomethylated HSP70 family stress-associated proteins. Structural and biochemical analyses reveal that PRMT7-driven in vitro methylation of HSP70 at R469 requires an ATP-bound, open conformation of HSP70. In cells, SGC3027 inhibits methylation of both constitutive and inducible forms of HSP70, and leads to decreased tolerance for perturbations of proteostasis including heat shock and proteasome inhibitors. These results demonstrate a role for PRMT7 and arginine methylation in stress response.


Assuntos
Arginina/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Proteína-Arginina N-Metiltransferases/metabolismo , Estresse Fisiológico , Animais , Técnicas de Silenciamento de Genes , Células HCT116 , Humanos , Metilação/efeitos dos fármacos , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Proteína-Arginina N-Metiltransferases/antagonistas & inibidores , Proteína-Arginina N-Metiltransferases/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Células Sf9
8.
Am J Physiol Renal Physiol ; 319(2): F215-F228, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32463727

RESUMO

Nitric oxide synthase inhibition by Nω-nitro-l-arginine methyl ester (l-NAME) plus a high-salt diet (HS) is a model of chronic kidney disease (CKD) characterized by marked hypertension and renal injury. With cessation of treatment, most of these changes subside, but progressive renal injury develops, associated with persistent low-grade renal inflammation. We investigated whether innate immunity, and in particular the NF-κB system, is involved in this process. Male Munich-Wistar rats received HS + l-NAME (32 mg·kg-1·day-1), whereas control rats received HS only. Treatment was ceased after week 4 when 30 rats were studied. Additional rats were studied at week 8 (n = 30) and week 28 (n = 30). As expected, HS + l-NAME promoted severe hypertension, albuminuria, and renal injury after 4 wk of treatment, whereas innate immunity activation was evident. After discontinuation of treatments, partial regression of renal injury and inflammation occurred, along with persistence of innate immunity activation at week 8. At week 28, glomerular injury worsened, while renal inflammation persisted and renal innate immunity remained activated. Temporary administration of the NF-κB inhibitor pyrrolidine dithiocarbamate, in concomitancy with the early 4-wk HS + l-NAME treatment, prevented the development of late renal injury and inflammation, an effect that lasted until the end of the study. Early activation of innate immunity may be crucial to the initiation of renal injury in the HS + l-NAME model and to the autonomous progression of chronic nephropathy even after cessation of the original insult. This behavior may be common to other conditions leading to CKD.


Assuntos
Arginina/análogos & derivados , Glomérulos Renais/efeitos dos fármacos , NF-kappa B/antagonistas & inibidores , Insuficiência Renal Crônica/tratamento farmacológico , Animais , Arginina/metabolismo , Inibidores Enzimáticos/farmacologia , Rim/efeitos dos fármacos , NG-Nitroarginina Metil Éster/farmacologia , Nefrite/fisiopatologia , Ratos Wistar , Insuficiência Renal Crônica/fisiopatologia , Cloreto de Sódio/farmacologia , Cloreto de Sódio na Dieta/farmacologia
9.
Proc Natl Acad Sci U S A ; 117(22): 12387-12393, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32409599

RESUMO

Microbiota, host and dietary metabolites/signals compose the rich gut chemical environment, which profoundly impacts virulence of enteric pathogens. Enterohemorrhagic Escherichia coli (EHEC) engages a syringe-like machinery named type-III secretion system (T3SS) to inject effectors within host cells that lead to intestinal colonization and disease. We previously conducted a high-throughput screen to identify metabolic pathways that affect T3SS expression. Here we show that in the presence of arginine, the arginine sensor ArgR, identified through this screen, directly activates expression of the genes encoding the T3SS. Exogenously added arginine induces EHEC virulence gene expression in vitro. Congruently, a mutant deficient in arginine transport (ΔartP) had decreased virulence gene expression. ArgR also augments murine disease caused by Citrobacter rodentium, which is a murine pathogen extensively employed as a surrogate animal model for EHEC. The source of arginine sensed by C. rodentium is not dietary. At the peak of C. rodentium infection, increased arginine concentration in the colon correlated with down-regulation of the host SLC7A2 transporter. This increase in the concentration of colonic arginine promotes virulence gene expression in C. rodentium Arginine is an important modulator of the host immune response to pathogens. Here we add that arginine also directly impacts bacterial virulence. These findings suggest that a delicate balance between host and pathogen responses to arginine occur during disease progression.


Assuntos
Citrobacter rodentium/metabolismo , Infecções por Enterobacteriaceae/microbiologia , Escherichia coli Êntero-Hemorrágica/metabolismo , Infecções por Escherichia coli/microbiologia , Regulação Bacteriana da Expressão Gênica , Animais , Arginina/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Citrobacter rodentium/genética , Citrobacter rodentium/patogenicidade , Escherichia coli Êntero-Hemorrágica/genética , Escherichia coli Êntero-Hemorrágica/patogenicidade , Humanos , Camundongos , Camundongos Endogâmicos C3H , Virulência , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
10.
Nucleic Acids Res ; 48(11): 5967-5985, 2020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32406921

RESUMO

During infection of a host, Pseudomonas aeruginosa orchestrates global gene expression to adapt to the host environment and counter the immune attacks. P. aeruginosa harbours hundreds of regulatory genes that play essential roles in controlling gene expression. However, their contributions to the bacterial pathogenesis remain largely unknown. In this study, we analysed the transcriptomic profile of P. aeruginosa cells isolated from lungs of infected mice and examined the roles of upregulated regulatory genes in bacterial virulence. Mutation of a novel regulatory gene pvrA (PA2957) attenuated the bacterial virulence in an acute pneumonia model. Chromatin immunoprecipitation (ChIP)-Seq and genetic analyses revealed that PvrA directly regulates genes involved in phosphatidylcholine utilization and fatty acid catabolism. Mutation of the pvrA resulted in defective bacterial growth when phosphatidylcholine or palmitic acid was used as the sole carbon source. We further demonstrated that palmitoyl coenzyme A is a ligand for the PvrA, enhancing the binding affinity of PvrA to its target promoters. An arginine residue at position 136 was found to be essential for PvrA to bind palmitoyl coenzyme A. Overall, our results revealed a novel regulatory pathway that controls genes involved in phosphatidylcholine and fatty acid utilization and contributes to the bacterial virulence.


Assuntos
Proteínas de Bactérias/metabolismo , Ácidos Graxos/química , Ácidos Graxos/metabolismo , Genes Bacterianos/genética , Pseudomonas aeruginosa/metabolismo , Pseudomonas aeruginosa/patogenicidade , Animais , Arginina/metabolismo , Sequência de Bases , Imunoprecipitação da Cromatina , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica , Ligantes , Camundongos , Modelos Moleculares , Mutação , Ácido Palmítico/metabolismo , Palmitoil Coenzima A/metabolismo , Fosfatidilcolinas/metabolismo , Pneumonia Bacteriana/microbiologia , Regiões Promotoras Genéticas , Pseudomonas aeruginosa/genética , Transcriptoma , Virulência/genética
11.
PLoS Pathog ; 16(4): e1008441, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32294136

RESUMO

Gut symbiotic bacteria have a substantial impact on host physiology and ecology. However, the contribution of gut microbes to host fitness during long-term low-temperature stress is still unclear. This study examined the role of gut microbiota in host low-temperature stress resistance at molecular and biochemical levels in the oriental fruit fly Bactrocera dorsalis. The results showed that after the gut bacteria of flies were removed via antibiotic treatment, the median survival time was significantly decreased to approximately 68% of that in conventional flies following exposure to a temperature stress of 10°C. Furthermore, we found that Klebsiella michiganensis BD177 is a key symbiotic bacterium, whose recolonization in antibiotic treated (ABX) flies significantly extended the median survival time to 160% of that in the ABX control, and restored their lifespan to the level of conventional flies. Notably, the relative levels of proline and arginine metabolites were significantly downregulated by 34- and 10-fold, respectively, in ABX flies compared with those in the hemolymph of conventional flies after exposure to a temperature stress of 10°C whereas recolonization of ABX flies by K. michiganensis BD177 significantly upregulated the levels of proline and arginine by 13- and 10- fold, respectively, compared with those found in the hemolymph of ABX flies. qPCR analysis also confirmed that K. michiganensis-recolonized flies significantly stimulated the expression of transcripts from the arginine and proline metabolism pathway compared with the ABX controls, and RNAi mediated silencing of two key genes Pro-C and ASS significantly reduced the survival time of conventional flies, postexposure low-temperature stress. We show that microinjection of L-arginine and L-proline into ABX flies significantly increased their survival time following exposure to temperature stress of 10°C. Transmission electron microscopy (TEM) analysis further revealed that low-temperature stress caused severe destruction in cristae structures and thus resulted in abnormal circular shapes of mitochondria in ABX flies gut, while the recolonization of live K. michiganensis helped the ABX flies to maintain mitochondrial functionality to a normal status, which is important for the arginine and proline induction. Our results suggest that gut microbiota plays a vital role in promoting the host resistance to low-temperature stress in B. dorsalis by stimulating its arginine and proline metabolism pathway.


Assuntos
Arginina/metabolismo , Microbioma Gastrointestinal , Prolina/metabolismo , Tephritidae/microbiologia , Animais , Temperatura Baixa , Klebsiella/genética , Klebsiella/crescimento & desenvolvimento , Klebsiella/isolamento & purificação , Klebsiella/fisiologia , Masculino , Estresse Fisiológico , Simbiose , Tephritidae/fisiologia
12.
Avian Dis ; 64(1): 16-22, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32267121

RESUMO

Hydropericardium syndrome (HPS) is caused by fowl adenovirus serotype 4 (FAdV-4). HPS has caused outbreaks in Chinese populations of broiler chickens since 2015. However, little is known about the molecular mechanisms underlying HPS. In this study, we used transcriptomic analysis to screen differentially expressed genes (DEGs) in the livers of FAdV-4-infected and noninfected chicks. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the gene network associated with the arginine metabolism pathway was enriched in livers infected by FAdV-4; 10 genes were downregulated and 8 genes were upregulated in these livers when compared to noninfected livers. The DEGs identified in livers were reanalyzed by real-time fluorescence quantitative PCR (qPCR); results indicated that the mRNA levels of the DEGs concurred with the data derived from KEGG analysis. Next, we used qPCR to detect the DEGs of the arginine metabolism pathway in a hepatocellular carcinoma cell line (LMH) after infection with FAdV-4 for 24 hr; this also indicated that the mRNA levels of the DEGs concurred with that seen in the liver. We also used si-RNA oligonucleotides to knock down the mRNA levels of iNOS in LMH cells infected with FAdV-4 and found that the viral load of FAdV-4 was increased. Further investigation revealed that the addition of 240 µg/ml of arginine into the culture medium of LMH cells infected with FAdV-4 for 24 hr led to a significant increase in the mRNA levels of iNOS but a significant reduction in the viral load of FAdV-4. Therefore, our data indicated that when broiler chickens become infected with FAdV-4, the arginine metabolic pathway in the liver becomes dysfunctional and the iNOS mRNA level decreases. This will add benefit to the replication of FAdV-4 but can be inhibited by the addition of an appropriate amount of arginine.


Assuntos
Infecções por Adenoviridae/veterinária , Arginina/metabolismo , Galinhas , Adenovirus A das Aves/fisiologia , Doenças das Aves Domésticas/virologia , Replicação Viral , Infecções por Adenoviridae/virologia , Animais , Feminino , Adenovirus A das Aves/classificação , Fígado/virologia , Sorogrupo , Carga Viral
13.
Proc Natl Acad Sci U S A ; 117(15): 8503-8514, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32234784

RESUMO

The specific interaction of importins with nuclear localization signals (NLSs) of cargo proteins not only mediates nuclear import but also, prevents their aberrant phase separation and stress granule recruitment in the cytoplasm. The importin Transportin-1 (TNPO1) plays a key role in the (patho-)physiology of both processes. Here, we report that both TNPO1 and Transportin-3 (TNPO3) recognize two nonclassical NLSs within the cold-inducible RNA-binding protein (CIRBP). Our biophysical investigations show that TNPO1 recognizes an arginine-glycine(-glycine) (RG/RGG)-rich region, whereas TNPO3 recognizes a region rich in arginine-serine-tyrosine (RSY) residues. These interactions regulate nuclear localization, phase separation, and stress granule recruitment of CIRBP in cells. The presence of both RG/RGG and RSY regions in numerous other RNA-binding proteins suggests that the interaction of TNPO1 and TNPO3 with these nonclassical NLSs may regulate the formation of membraneless organelles and subcellular localization of numerous proteins.


Assuntos
Núcleo Celular/metabolismo , Sinais de Localização Nuclear , Fragmentos de Peptídeos/metabolismo , Proteínas de Ligação a RNA/metabolismo , beta Carioferinas/metabolismo , Transporte Ativo do Núcleo Celular , Arginina/química , Arginina/metabolismo , Citoplasma/metabolismo , Glicina/química , Glicina/metabolismo , Células HeLa , Humanos , Fragmentos de Peptídeos/química , Ligação Proteica , Conformação Proteica , Proteínas de Ligação a RNA/química , Serina/química , Serina/metabolismo , Tirosina/química , Tirosina/metabolismo , beta Carioferinas/química
14.
Poult Sci ; 99(4): 1862-1874, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32241466

RESUMO

This study was conducted to investigate the effects of dietary arginine (Arg) supplementation on the inflammatory response and gut microbiota of broiler chickens subjected to Salmonella enterica serovar Typhimurium. One hundred and forty 1-day-old Arbor Acres male birds were randomly assigned to a 2 × 2 factorial arrangement including diet treatment (with or without 0.3% Arg supplementation) and immunological stress (with or without S. typhimurium challenge). Samples were obtained at 7 D after infection (day 23). Results showed that S. typhimurium challenge caused histopathological and morphological damages, but Arg addition greatly reduced these intestinal injuries. S. typhimurium challenge elevated the levels of serum inflammatory parameters, including diamine oxidase, C-reactive protein, procalcitonin, IL-1ß, IL-8, and lipopolysaccharide-induced tumor necrosis factor-alpha factor (LITNF) homolog. However, Arg supplementation decreased the serum procalcitonin, IL-1ß, IL-8, and LITNF concentration. S. typhimurium challenge significantly increased jejunal IL-1ß, IL-8, IL-10, and IL-17 mRNA expression and tended to upregulate IL-22 mRNA expression, but Arg supplementation remarkably reduced IL-8 mRNA expression, tended to downregulate IL-22 mRNA expression, and dramatically elevated IFN-γ and IL-10 mRNA expression. In addition, sequencing data of 16S rDNA indicated that the population of Proteobacteria phylum; Enterobacteriaceae family; Escherichia-Shigella, and Nitrosomonas genera; and Escherichia coli and Ochrobactrum intermedium species were more abundant, but the population of Rhodocyclaceae and Clostridiaceae_1 families and Candidatus Arthromitus genus were less abundant in the ileal digesta of birds with only S. typhimurium infection when compared with the controls. Treatment with Arg in birds subjected to S. typhimurium challenge increased the abundances of Firmicutes phylum, Clostridiaceae_1 family, Methylobacterium and Candidatus Arthromitus genera but decreased the abundance of Nitrosomonas genus and Rhizobium cellulosilyticum and Rubrobacter xylanophilus species as compared with the only S. typhimurium-challenged birds. In conclusion, Arg supplementation can alleviate intestinal mucosal impairment by ameliorating inflammatory response and modulating gut microbiota in broiler chickens challenged with S. typhimurium.


Assuntos
Arginina/metabolismo , Fenômenos Fisiológicos Bacterianos , Galinhas/imunologia , Microbioma Gastrointestinal/fisiologia , Inflamação/veterinária , Salmonella typhimurium/fisiologia , Ração Animal/análise , Animais , Arginina/administração & dosagem , Galinhas/microbiologia , Dieta/veterinária , Suplementos Nutricionais/análise , Inflamação/tratamento farmacológico , Inflamação/microbiologia , Intestinos/anatomia & histologia , Intestinos/microbiologia , Intestinos/patologia , Masculino , Doenças das Aves Domésticas/microbiologia , Distribuição Aleatória , Salmonelose Animal/microbiologia , Estresse Fisiológico/imunologia
15.
Vet Res ; 51(1): 50, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32264939

RESUMO

Two experiments were performed to investigate the effect of different ratios of arginine (Arg) to lysine (Lys) in diets with low (30% Lys; Experiment 1) and high (45% Lys; Experiment 2) methionine (Met) levels on selected metabolic parameters, oxidative and epigenetic DNA damage, and the mechanisms underlying intestinal barrier integrity in turkeys challenged with Clostridium perfringens. In each experiment, 108 one-day-old Hybrid Converter female turkeys were placed in 6 pens (18 birds per pen) and reared for 42 days. At 34, 36 and 37 days of age, half of the birds were subjected to C. perfringens challenge. A 3 × 2 factorial design with three levels of Arg relative to Lys (90, 100 and 110%; Arg90, Arg100 and Arg110, respectively) and C. perfringens infection (-, +) was employed. Challenging birds with C. perfringens increased lipid oxidation and the oxidation and methylation of DNA of intestinal mucosa, and down-regulated the activities of DNA-repairing enzymes. Neither the dietary treatment nor the challenge affected the markers of liver function or metabolism. Arg110 diets with the high Met level induced DNA oxidation and methylation whereas these processes were downregulated in birds fed Arg90 diets. The results indicate that Arg90 diets with high Met levels have a beneficial influence on the indicators of intestinal barrier integrity in turkeys with necrotic enteritis (NE). Despite the analyzed amino acid ratios interacted with the systems responsible for the maintenance of gut integrity in the host organism, this dietary intervention probably enabled birds to cope with NE.


Assuntos
Arginina/metabolismo , Doenças das Aves/fisiopatologia , Infecções por Clostridium/veterinária , Clostridium perfringens/fisiologia , Lisina/metabolismo , Metionina/metabolismo , Ração Animal/análise , Animais , Arginina/administração & dosagem , Proteínas Aviárias/metabolismo , Doenças das Aves/microbiologia , Infecções por Clostridium/microbiologia , Infecções por Clostridium/fisiopatologia , Dano ao DNA , Dieta/veterinária , Suplementos Nutricionais/análise , Epigênese Genética , Expressão Gênica , Lisina/administração & dosagem , Metionina/administração & dosagem , Estresse Oxidativo , Distribuição Aleatória , Proteínas de Junções Íntimas/metabolismo
16.
Life Sci ; 248: 117471, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32112868

RESUMO

AIMS: This study aimed to explore the protective effects and possible mechanisms of baicalein on Aß25-35-induced toxicity. MAIN METHODS: Thioflavin-T (Th-T) dye was used to determine the effects of baicalein on Aß25-35 aggregation in vitro. PC12 cells were stimulated with Aß25-35, then the effects of baicalein on apoptosis, mitochondrial membrane potential (MMP), adenosine triphosphate (ATP), mitochondrial respiratory complex I, reactive oxygen species (ROS) and nitric oxide (NO) levels were determined. Moreover, LC-MS metabolomics approach was used to detect metabolic changes induced by baicalein in Aß25-35-injured PC12 cells. KEY FINDINGS: The results showed that baicalein could inhibit the aggregation of Aß25-35 in vitro. Furthermore, pretreatment with baicalein significantly prevented Aß25-35-induced cell apoptosis, as manifested by increasing the levels of MMP, ATP and mitochondrial respiratory complex I, decreasing the contents of ROS and NO. LC-MS metabolomics revealed that baicalein can regulate 5 metabolites, mainly involving two metabolic pathways, arginine and proline metabolism, nicotinate and nicotinamide metabolism. SIGNIFICANCE: Our study revealed that baicalein has a protective effect on Aß25-35-induced neurotoxicity in PC12 cells, which may be related to inhibition of apoptosis and metabolic disorders.


Assuntos
Peptídeos beta-Amiloides/antagonistas & inibidores , Apoptose/efeitos dos fármacos , Flavanonas/farmacologia , Mitocôndrias/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fragmentos de Peptídeos/antagonistas & inibidores , Trifosfato de Adenosina/biossíntese , Peptídeos beta-Amiloides/toxicidade , Animais , Arginina/metabolismo , Complexo I de Transporte de Elétrons/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Niacina/metabolismo , Niacinamida/metabolismo , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Fragmentos de Peptídeos/toxicidade , Prolina/metabolismo , Agregados Proteicos/efeitos dos fármacos , Ratos , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo
17.
Gene ; 742: 144593, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32199949

RESUMO

Protein arginine methyltransferase 1 (PRMT1) and the product of this enzyme (histone H4 asymmetrically dimethylated at Arg 3; H4R3me2a) are important in the establishment and maintenance of chicken and murine erythrocyte transcriptionally active chromatin. Silencing the expression of PRMT1 results in loss of acetylated histones H3 and H4 and methylated H3K4 and prevents erythropoiesis. Here, we show that H4R3me2a and the PRMT5-catalyzed histone H3 symmetrically dimethylated at Arg 2 (H3R2me2s) locate largely to introns of expressed genes and intergenic regions, with both marks co-localizing in the chicken polychromatic erythrocyte genome. H4R3me2a and H3R2me2s were associated with histone marks of active promoters and enhancers, as well as with the body of genes that have an atypical chromatin structure, with nucleosome depleted regions. H4R3me2a co-localized with acetylated H3K27. Previous studies have shown that PRMT1 was bound to CBP/p300, suggesting a role of PRMT1-mediated H4R3me2a in CBP/p300 recruitment and H3K27 acetylation. Moreover, PRMT1 might be a key enzyme affected when S-adenosyl methionine levels are reduced in metabolic disorders.


Assuntos
Código das Histonas/genética , Histonas/metabolismo , Nucleossomos/metabolismo , Proteína-Arginina N-Metiltransferases/metabolismo , Reticulócitos/metabolismo , Animais , Arginina/metabolismo , Galinhas , Cromatina/metabolismo , Feminino , Histonas/genética , Metilação , Nucleossomos/genética , Transcrição Genética
18.
Food Chem ; 320: 126619, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32203836

RESUMO

The fermentation of mare's milk into koumiss produces many beneficial functional compounds depending on the metabolism of the initial microbial flora. In this study, metabolites found in mare's milk and resulting koumiss were identified. Major metabolic pathways in the fermentation were also identified using an UPLC-Q-TOF-MS-based metabolomics method. In total, 354 metabolites were identified: 61 were up-regulated and 105 were down-regulated. Metabolic pathway analyses revealed that c-5-branched dibasic acid metabolism, valine, leucine and isoleucine degradation, arginine and proline metabolism, valine, leucine and isoleucine biosynthesis, vascular smooth muscle contraction, aminoacyl-tRNA biosynthesis and ß-alanine metabolism showed significant increases. A hierarchical cluster analysis of metabolites indicated a clear grouping pattern in which the relative concentrations of p-pyruvate, 20-HETE, 4-aminobutanoate, uracil, acetoacetate, and γ-linolenic acid differed significantly between milk and koumiss. This study provides reference values for metabolic isolates and bioactive compounds purification in mare's milk and koumiss.


Assuntos
Kumis/análise , Metabolômica , Leite/química , Animais , Arginina/química , Arginina/metabolismo , Cromatografia Líquida de Alta Pressão , Feminino , Fermentação , Cavalos , Leucina/química , Leucina/metabolismo , Espectrometria de Massas , Leite/metabolismo , Valina/química , Valina/metabolismo
19.
Phytother Res ; 34(8): 2023-2031, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32144833

RESUMO

The present study sought to investigate the effect of micronized resveratrol supplementation on serum levels of asymmetric de-methyl-arginine (ADMA) and paraoxonase-1 (PON1) activity in patients with type 2 diabetes (T2D). In this double-blinded randomized trial, 76 patients with T2D were recruited. Participants were randomly assigned to consume 1,000 mg resveratrol or placebo capsules (methylcellulose) per day, for 8 weeks. Serum levels of ADMA and PON1 enzyme activity were measured at the beginning and end of the intervention using the enzyme-linked immunosorbent assay method. In total, 71 participants completed the study. Our results showed that resveratrol significantly decreased serum levels of ADMA (-0.16 ± 0.11, p < .001) and improved PON1 enzyme activity (15.39 ± 13.99, p < .001) compared with placebo, after adjusting for confounding factors (age, sex, and baseline body mass index). Our findings suggest that 8-week resveratrol supplementation may produce beneficial effects on serum levels of ADMA and PON1 enzyme activity in patients with T2DM. However, further research is needed to confirm the veracity of these results.


Assuntos
Arginina/sangue , Arildialquilfosfatase/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Resveratrol/química , Adulto , Arginina/metabolismo , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resveratrol/uso terapêutico
20.
J Phys Chem Lett ; 11(6): 2363-2368, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32130014

RESUMO

Although colloidal nanoparticles are known to enter into cells via endocytosis, the direct membrane permeation of nanoparticles is rarely reported, and the underlying mechanism of direct membrane permeation is largely unsolved. However, a direct membrane-penetrating nanoparticle has great advantage as a delivery carrier that offers high delivery efficiency, faster delivery kinetics, and minimal lysosomal degradation. Here we show that arginine-terminated Au nanoparticles of <10 nm size enter via energy-independent direct membrane penetration, but as the size increases, the nanoparticles switch to energy-dependent endocytotic uptake. As a delivery carrier, <10 nm Au nanoparticles directly transport an electrostatically bound protein into the cytosol within a minute and allow direct access of the protein to subcellular compartments. This direct delivery approach has been used for efficient nuclear targeting of proteins and can be adapted for direct cytosolic delivery or subcellular targeting applications with high efficiency.


Assuntos
Arginina/metabolismo , Núcleo Celular/metabolismo , Peptídeos Penetradores de Células/metabolismo , Citosol/metabolismo , Nanopartículas/metabolismo , Humanos
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