Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 332
Filter
1.
Article in Chinese | WPRIM | ID: wpr-921528

ABSTRACT

Objective To obtain the proteome and acetylome profiles of livers in mice during normal aging.Methods We applied tandem mass tag labeling and liquid chromatography tandem mass spectrometry and achieved proteome and acetylome data in C57BL/6J male mice aged 2 and 18 months under physiological conditions.Results A total of 4712 proteins were quantified by proteome profiling,and 4818 acetylated sites in 1367 proteins by acetylome profiling.The proteome and acetylome revealed moderate differences in the livers of young and old mice.There were 195 differentially expressed proteins in the proteome and 113 differentially expressed acetylated sites corresponding to 76 proteins in the acetylome.Functional enrichment analysis for the proteome showed that aging-associated upregulated proteins were mainly involved in fatty acid metabolism,epoxygenase P450 pathway,drug catabolic process,organic hydroxy compound metabolic process,and arachidonic acid metabolic process,while the downregulated proteins were related to regulation of gene silencing,nucleosome assembly,protein heterotetramerization,response to interferon,protein-DNA complex assembly and other processes.For the acetylome,the proteins with aging-associated upregulated acetylated sites mainly participated in cofactor metabolism,small molecule catabolic process,ribose phosphate metabolic process,ribonucleotide metabolic process,and purine-containing compound metabolic process,while the proteins with downregulated acetylated sites were associated with sulfur compound metabolic process,response to unfolded protein,and amino acid metabolic process.Conclusion We profiled the proteome and acetylome of livers in mice during normal aging and generated datasets for further research on aging.


Subject(s)
Acetylation , Aging , Animals , Liver , Lysine/metabolism , Male , Mice , Mice, Inbred C57BL , Proteome/metabolism
2.
Article in Chinese | WPRIM | ID: wpr-878883

ABSTRACT

Nano-LC MS/MS was used to analyze trypsin digested deer-hide gelatin(DHG) samples, hydroxylation and O-glycosylation on lysine sites of DHG were comprehensive identified by using PEAKS Studio software. The sites, sorts and amounts of hydroxylation and O-glycosylation on Type Ⅰ collagen α1 chain(COL1 A1) and α2 chain(COL1 A2) of DHG were revealed. As a result, 5 284 peptides were identified from DHG samples, which were mainly from COL1 A1 and COL1 A2. Among these peptides, there were 449 peptides with hydroxylysine, 442 with galactosyl-hydroxylysine, 449 with glucosyl-galactosyl-hydroxylysine. The major modified sites of hydroxylation and O-glycosylation in DHG were shown as follow: α1-9 N and α2-5 N in N-telopeptides, α1-87, α1-174, α1-930, α2-87, α2-174, α2-933 in triple helix domain, and α1-16 C in C-telopeptides. These hydroxylation and O-glycosylation were correlated with the formation and stability of collagen molecules and collagen fibrils. It is feasible for the collagens and peptides dissolving from deer skin collagen fibrils under high temperature and pressure decocting, high temperature and pressure also might destroy inter-molecular covalent cross-linking and help those glycol-peptides formations. The present study provided ideas and strategies for the in-depth investigation on DHG chemical constituents, and showed good theoretical significance and application value.


Subject(s)
Animals , Deer/metabolism , Gelatin , Glycosylation , Hydroxylation , Lysine/metabolism , Protein Processing, Post-Translational , Tandem Mass Spectrometry
3.
Arq. bras. med. vet. zootec. (Online) ; 72(6): 2321-2330, Nov.-Dec. 2020. tab
Article in Portuguese | LILACS, VETINDEX | ID: biblio-1142287

ABSTRACT

Objetivou-se avaliar a inclusão de níveis de lisina e metionina protegidas na dieta sobre os parâmetros nutricionais e metabólicos energéticos e hepáticos de borregas em crescimento. Utilizaram-se cinco borregas ½ sangue Dorper x Santa Inês, com aproximadamente oito meses de idade e peso médio de 50 ± 2,3kg, distribuídas em esquema quadrado latino 5x5 (cinco tratamentos, cinco animais e cinco períodos). Os tratamentos consistiram na inclusão de diferentes níveis de lisina e metionina protegidas da degradação ruminal (MicroPEARLS LM®) na ração, sendo: 0g, 8g, 16g, 24g e 32g por dia. A dieta era composta por silagem de milho e concentrado na relação 30V:70C. Realizou-se um ensaio de digestibilidade para determinar consumo e digestibilidade da matéria seca (CMS/DGMS), balanço de nitrogênio e metabólitos sanguíneos. O CMS (kg/dia) em relação ao peso metabólico apresentou equação linear positiva, sendo maior no tratamento que ofertou 32g de aminoácidos por dia, assim como o nitrogênio ingerido e o balanço de nitrogênio, sendo positivo em todos os tratamentos. Não houve diferença (P>0,05) para a digestibilidade da MS e o metabolismo energético e hepático. Lisina e metionina protegidas da degradação ruminal podem ser incluídas na ração de borregas em crescimento até 32g/dia sem causar efeitos negativos na digestibilidade da MS e no metabolismo.(AU)


The objective was to evaluate the inclusion of protected lysine and methionine levels on the diet, over the nutritional parameters and energetic and hepatic metabolites of growing lambs. Five lambs ½ blood Dorper x Santa Inês, with approximately eight months of age and average weight of 50kg, were distributed in a 5x5 latin square scheme (five treatments and five replicates). The treatments consisted of the inclusion of different levels of lysine and methionine protected from ruminal degradation (MicroPEARLS LM®) in the diet, being: 0g, 8g, 16g, 24g and 32g. The diet was composed of corn silage and concentrated 30V:70C in the ratio. A digestibility assay was performed to determine dry matter intake and digestibility (DMI/DDMI), nitrogen balance and blood metabolites. The DMI (kg/day) in relation to the metabolic weight had a positive linear equation, being higher in treatment 32g, as well as the ingested nitrogen and nitrogen balance, being positive in all treatments. There was no difference (P>0.05) for the digestibility of DM, energetic and hepatic metabolism. Lysine and methionine protected from ruminal degradation can be included in the diet of growing lambs up to 32g without causing negative effects on DM digestibility and metabolism.(AU)


Subject(s)
Animals , Female , Sheep/metabolism , Energy Metabolism , Liver/metabolism , Lysine/administration & dosage , Methionine/administration & dosage , Nutrition Assessment
4.
Arq. bras. med. vet. zootec. (Online) ; 72(4): 1305-1312, July-Aug. 2020. tab
Article in Portuguese | LILACS, VETINDEX | ID: biblio-1131487

ABSTRACT

Objetivou-se avaliar níveis de proteína e aminoácidos, mantendo-se as relações entre os aminoácidos para suínos machos, castrados, de30kg a 50kg. Foram utilizados 50 suínos machos, castrados, com peso inicial de 30,35±1,96kg, distribuídos em delineamento experimental inteiramente ao acaso, com cinco tratamentos e cinco repetições com dois animais por unidade experimental. Os tratamentos consistiram em níveis de lisina digestível, mantendo-se a relação com os demais aminoácidos digestíveis: 0,73%; 0,83%; 0,93%; 1,03% e 1,13% na dieta. Avaliou-se desempenho, avaliação de carcaça, parâmetros sanguíneos e digestibilidade das dietas. Houve efeito quadrático para ganho de peso, conversão alimentar e níveis de creatinina em função dos níveis de lisina, com níveis ótimos estimados em 0,92%, 0,93% e 0,93%, respectivamente. As características de carcaça não foram influenciadas significativamente pelos tratamentos. Constatou-se efeito linear positivo para digestibilidade aparente da proteína bruta, da proteína total e da ureia sérica. Conclui-se que os níveis de proteína e lisina digestível recomendados para dietas de suínos machos, castrados, da raça Duroc, na fase de crescimento I, são de 16,70% e 0,93%, respectivamente, pois esses níveis proporcionaram melhorias no ganho de peso, na conversão alimentar e na creatinina sérica.(AU)


The objective of this study was to evaluate digestible lysine levels, keeping the relation among amino acids for Duroc barrows from 30 to 50kg. Fifty Duroc barrows (30.35±1.96kg live weight) were allotted in a completely randomized experimental design, divided in five treatments with five replicates and two animals in each experimental unit. The treatments consisted of digestible lysine levels (0.73%; 0.83%; 0.93%; 1.03% and 1.13%), keeping the relation with other essential amino acids. Performance, carcass characteristics, blood parameters and digestibility of the diets were evaluated. There was a quadratic response on weight gain, feed conversion and creatinine serum concentration as a function of the digestible lysine levels, with the greater levels obtained at 0.92%, 0.93% and 0.93%, respectively. The carcass characteristics were not influenced by the treatments. There was a linear increase of apparent digestibility of crude protein, total serum protein and urea. Results suggest that the requirement of protein and digestible lysine was 16.70% and 0.93%, respectively, providing improvements on weight gain, feed conversion and creatinine serum concentration of Duroc barrows in the growth phase.(AU)


Subject(s)
Animals , Male , Swine , Blood , Weight Gain , Diet , Lysine , Creatinine , Amino Acids, Essential
5.
Arq. bras. med. vet. zootec. (Online) ; 72(3): 1017-1026, May-June, 2020. tab
Article in Portuguese | LILACS, VETINDEX | ID: biblio-1129721

ABSTRACT

O objetivo deste estudo foi determinar a exigência de lisina digestível para frangos de corte machos sob as características de desempenho, composição corporal e rendimento de carcaça dos animais, de 22 a 42 dias de idade. As dietas diferiram quanto aos níveis de lisina digestível, mantendo-se a relação dos demais aminoácidos com a lisina. Foram utilizados seis níveis de lisina digestível: 0,88%; 0,96%; 1,05%; 1,13%; 1,22%; e 1,30%. Distribuídos em 36 unidades experimentais de 36 aves cada, 1296 animais da linhagem Cobb - 500® tiveram as seguintes características de desempenho avaliadas: consumo de ração (CR), peso corporal (PC), ganho de peso (GP), conversão alimentar (CA), viabilidade criatória (VC) e índice de eficiência produtiva (IEP). Aos 42 dias de idade, foram selecionadas ao acaso cinco aves para avaliação do rendimento de carcaça, e duas para avaliação da composição corporal. A CA, o IEP e o rendimento de peito foram influenciados, sendo sua exigência de 1,30%, sugerindo que níveis maiores de lisina digestível que as recomendações utilizadas como base neste estudo (1,13%) trouxeram benefícios aos animais sobre essas características.(AU)


The objective of the present study was to evaluate the optimal levels of digestible lysine in the diet of male broilers, evaluating performance characteristics, body composition, and carcass yield of the animals in the final phase (22 to 42 days old). The diets differed in digestible lysine content, maintaining the relation among the other amino acids and lysine in accordance with the ideal protein concept. The six levels of digestible lysine in the diet were: 0.88%; 0.96%; 1.05%; 1.13%; 1.22%, and 1.30%. A total of 1296 animals were employed, distributed in 36 experimental units of 36 birds each. The determined performance characteristics corresponded to feed intake (FI), body weight (BW), weight gain (WG), feed conversion (FC), viability (VB), and productive efficiency index (PEI). At 42 days of age seven birds per experimental unit were selected at random, five for the estimation of yield and total carcass and commercial cut weight, and two for the evaluation of body composition. FC, animal breast yield and PEI weres influenced with requirements of 1.30%. With respect to nationally known recommendations regarding digestible lysine (1.13%), higher levels of the amino acid in the diet have brought benefits regarding the characteristics above.(AU)


Subject(s)
Animals , Male , Chickens/metabolism , Amino Acids/administration & dosage , Animal Feed , Lysine/administration & dosage
6.
Article in English | WPRIM | ID: wpr-880485

ABSTRACT

Ubiquitination, an essential post-transcriptional modification (PTM), plays a vital role in nearly every biological process, including development and growth. Despite its functions in plant reproductive development, its targets in rice panicles remain unclear. In this study, we used proteome-wide profiling of lysine ubiquitination in rice (O. sativa ssp. indica) young panicles. We created the largest ubiquitinome dataset in rice to date, identifying 1638 lysine ubiquitination sites on 916 unique proteins. We detected three conserved ubiquitination motifs, noting that acidic glutamic acid (E) and aspartic acid (D) were most frequently present around ubiquitinated lysine. Enrichment analysis of Gene Ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of these ubiquitinated proteins revealed that ubiquitination plays an important role in fundamental cellular processes in rice young panicles. Interestingly, enrichment analysis of protein domains indicated that ubiquitination was enriched on a variety of receptor-like kinases and cytoplasmic tyrosine and serine-threonine kinases. Furthermore, we analyzed the crosstalk between ubiquitination, acetylation, and succinylation, and constructed a potential protein interaction network within our rice ubiquitinome. Moreover, we identified ubiquitinated proteins related to pollen and grain development, indicating that ubiquitination may play a critical role in the physiological functions in young panicles. Taken together, we reported the most comprehensive lysine ubiquitinome in rice so far, and used it to reveal the functional role of lysine ubiquitination in rice young panicles.


Subject(s)
Acetylation , Lysine/metabolism , Oryza/metabolism , Plant Proteins/metabolism , Protein Interaction Maps , Protein Processing, Post-Translational , Proteome/metabolism , Ubiquitin/metabolism , Ubiquitination
7.
Article in English | WPRIM | ID: wpr-880483

ABSTRACT

Protein lysine methylation is a prevalent post-translational modification (PTM) and plays critical roles in all domains of life. However, its extent and function in photosynthetic organisms are still largely unknown. Cyanobacteria are a large group of prokaryotes that carry out oxygenic photosynthesis and are applied extensively in studies of photosynthetic mechanisms and environmental adaptation. Here we integrated propionylation of monomethylated proteins, enrichment of the modified peptides, and mass spectrometry (MS) analysis to identify monomethylated proteins in Synechocystis sp. PCC 6803 (Synechocystis). Overall, we identified 376 monomethylation sites in 270 proteins, with numerous monomethylated proteins participating in photosynthesis and carbon metabolism. We subsequently demonstrated that CpcM, a previously identified asparagine methyltransferase in Synechocystis, could catalyze lysine monomethylation of the potential aspartate aminotransferase Sll0480 both in vivo and in vitro and regulate the enzyme activity of Sll0480. The loss of CpcM led to decreases in the maximum quantum yield in primary photosystem II (PSII) and the efficiency of energy transfer during the photosynthetic reaction in Synechocystis. We report the first lysine monomethylome in a photosynthetic organism and present a critical database for functional analyses of monomethylation in cyanobacteria. The large number of monomethylated proteins and the identification of CpcM as the lysine methyltransferase in cyanobacteria suggest that reversible methylation may influence the metabolic process and photosynthesis in both cyanobacteria and plants.


Subject(s)
Bacterial Proteins/metabolism , Lysine/metabolism , Methyltransferases/metabolism , Photosynthesis , Protein Processing, Post-Translational , Synechocystis/growth & development
8.
Article in English | WPRIM | ID: wpr-811061

ABSTRACT

PURPOSE: Reduction-oxidation reaction homeostasis is vital for regulating inflammatory conditions and its dysregulation may affect the pathogenesis of chronic airway inflammatory diseases such as asthma. Peroxiredoxin-6, an important intracellular anti-oxidant molecule, is reported to be highly expressed in the airways and lungs. The aim of this study was to analyze the expression pattern of peroxiredoxin-6 in the peripheral blood mononuclear cells (PBMCs) of asthmatic patients and in bronchial epithelial cells (BECs).METHODS: The expression levels and modifications of peroxiredoxin-6 were evaluated in PBMCs from 22 asthmatic patients. Phosphorylated and acetylated peroxiredoxin-6 in hydrogen peroxide-treated human BECs was detected using immunoprecipitation analysis. The expression level of peroxiredoxin-6 was also investigated in BECs treated with hydrogen peroxide. Cycloheximide and proteasome inhibitors were used to determine whether peroxiredoxin-6 is degraded by proteasomes.RESULTS: Peroxiredoxin-6 expression was significantly reduced in the PBMCs of asthmatic patients compared to control subjects. Distinct modification patterns for peroxiredoxin-6 were observed in the PBMCs of asthmatic patients using 2-dimensional-electrophoresis. The levels of phosphorylated serine and acetylated lysine in peroxiredoxin-6 were significantly increased in the BECs following hydrogen peroxide treatment. The level of peroxiredoxin-6 expression was reduced in hydrogen peroxide-stimulated BECs, presumably due to proteasomes.CONCLUSIONS: The expression of peroxiredoxin-6, which is down-regulated in the immune cells of asthmatic patients and BECs, can be modified by oxidative stress. This phenomenon may have an effect on asthmatic airway inflammation.


Subject(s)
Asthma , Cycloheximide , Epithelial Cells , Homeostasis , Humans , Hydrogen , Hydrogen Peroxide , Immunoprecipitation , Inflammation , Lung , Lysine , Oxidative Stress , Proteasome Inhibitors , Protein Processing, Post-Translational , Serine
9.
Rev. MVZ Córdoba ; 24(3): 7346-7354, sep.-dic. 2019. tab
Article in Spanish | LILACS | ID: biblio-1115260

ABSTRACT

RESUMEN Objetivos. El objetivo de este trabajo fue estimar en vacas en pastoreo, tanto la reproducibilidad como la precisión del balance de metionina (Met) y lisina (Lis), aminoácidos más limitantes en la producción de leche, cuando se comparan los valores predichos versus los valores observados. Materiales y métodos. Se usaron 12 vacas durante un periodo de 20 días. Control: animales pastoreando y suplementados con alimento balanceado; Met-Lis: igual al control y el suplemento se ajustó con Lis y Met protegida. Para los valores predichos para la suplementación de Met y Lis, se tuvo en cuenta el promedio del consumo de materia seca (CMS) del hato, basado en la oferta y el consumo de pasto y los valores de proteína microbiana. Los valores observados se determinaron con base en el CMS individual usando marcadores externos e internos, además, la producción individual de proteína microbiana. Se realizó una prueba de t pareada y un modelo de predicción para determinar la eficiencia fue determinado usando el error cuadrático medio de predicción (ECMP) y el coeficiente de concordancia (CCC). Resultados. Se encontraron diferencias significativas entre la suplementación y el balance de Met y Lis, entre los valores predichos y los valores observados para el CMS del forraje, la digestibilidad de la proteína microbiana, la producción de proteína microbiana, el suministro y el balance de Lis y Met. El CCC del balance de Lis y Met fue bajo (0.10), el ECMP fue alto, excepto para el CMS, que tuvo una concordancia moderada (0.63) y un bajo ECMP(4.42). Conclusiones. Estos resultados demuestran la falta de precisión de las herramientas que se usan para balancear las raciones individuales de vacas en pastoreo, ya que subestiman la suplementación y el balance de los aminoácidos.


ABSTRACT Objective. The aim of this study was to determine in grazing cows, the reproducibility and accuracy of the balance between predicted values, when compared with the observed values for the most limiting amino acids in milk protein synthesis, the methionine (Met) and Lysine (Lys). Materials and methods. Twelve lactating cows were used for a 20-day experimental period. Control: animals grazing and supplemented with balanced food; Met-Lys: same as control and supplemented with adjusted rumen protected Met and Lys. For Met and Lys supply predicted values, it was taking in account the average of the dry matter intake (DMI) of the herd, based in offer and foraging control and values of microbial protein data. Observed values were determined based in the individual DMI intake, using external and internal markers and the individual microbial protein production. A t-paired-sample test was performed and the efficiency of the model's prediction was determined using the mean square prediction error (MSPE) and the concordance coefficient (CCC). Results. Significant differences were found between the predicted and observed values for DMI forage, digestible microbial protein and microbial protein production, supply and the balance of Lys and Met. The CCC for Lys and Met balance were low (0.10), the MSPE was high except for the total DMI with a moderate concordance (0.63) and low MSPE (4.42). Conclusions. These results indicate a lack of precision of the tools, which underestimates the supply and balance of amino acids in individual grazing cows.


Subject(s)
Animals , Cattle , Cattle , Amino Acids, Essential , Lysine , Methionine
10.
Article in Chinese | WPRIM | ID: wpr-774068

ABSTRACT

Lysinuric protein intolerance (LPI) is an autosomal recessive disorder caused by SLC7A7 gene mutation and often involves severe lesions in multiple systems. Lung involvement is frequently seen in children with LPI and such children tend to have a poor prognosis. This article summarizes the clinical manifestations and gene mutation characteristics of three children diagnosed with LPI by SLC7A7 gene analysis. All three children had the manifestations of aversion to protein-rich food after weaning, delayed development, anemia, hepatosplenomegaly, and osteoporosis, as well as an increase in orotic acid in urine. In addition, interstitial pneumonia and diffuse pulmonary interstitial lesions were observed in two children. SLC7A7 gene detection showed three pathogenic mutations in these children, namely c.1387delG(p.V463CfsX56), c.1215G>A(p.W405X) and homozygous c.625+1G>A. After a definite diagnosis was made, all three children were given a low-protein diet and oral administration of citrulline [100 mg/(kg.d)], iron protein succinylate [4 mg/(kg.d)], calcium and zinc gluconates oral solution (10 mL/day) and vitamin D (400 IU/day). In addition, patient 3 was given prednisone acetate (5 mg/day). The children had varying degrees of improvement in symptoms and signs. It is hard to distinguish LPI from urea cycle disorder due to the features of amino acid and organic acid metabolism in LPI, and SLC7A7 gene analysis is the basis for a definite diagnosis of LPI.


Subject(s)
Amino Acid Metabolism, Inborn Errors , Genetics , Child , Citrulline , Fusion Regulatory Protein 1, Light Chains , Genetics , Humans , Lysine , Mutation
11.
Article in Chinese | WPRIM | ID: wpr-771404

ABSTRACT

As a member of the Sirtuins family in mammals, SIRT7 locates in nucleus and is a highly specific H3K18Ac (acetylated lysine 18 of histone H3) deacetylase. Recent studies showed that SIRT7 could participate in the ribosomal RNA transcription, cell metabolism, cell stress and DNA damage repair through various signaling pathways. In addition, SIRT7 is also closely related with aging, heart disease and fatty liver. In particular, SIRT7 plays important roles in the regulation of initiation and development of various tumors, such as liver cancer, gastric cancer, breast cancer, bladder cancer, colorectal cancer, and head/neck squamous cell carcinoma. This review describes the cellular and molecular functions of SIRT7, and systematically summarizes recent progress of SIRT7 in human disease.


Subject(s)
Animals , Histones , Humans , Lysine , Neoplasms , Signal Transduction , Sirtuins , Metabolism
12.
Article in English | WPRIM | ID: wpr-760610

ABSTRACT

BACKGROUND/OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disease triggered by epigenetic alterations, including lysine acetylation at histone or non-histone proteins, affecting the stability or transcription of lipogenic genes. Although various natural dietary compounds have anti-lipogenic effects, their effects on the acetylation status and lipid metabolism in the liver have not been thoroughly investigated. MATERIALS/METHODS: Following oleic-palmitic acid (OPA)-induced lipid accumulation in HepG2 cells, the acetylation status of histone and non-histone proteins, HAT activity, and mRNA expression of representative lipogenic genes, including PPARγ, SREBP-1c, ACLY, and FASN, were evaluated. Furthermore, correlations between lipid accumulation and HAT activity for 22 representative natural food extracts (NExs) were evaluated. RESULTS: Non-histone protein acetylation increased following OPA treatment and the acetylation of histones H3K9, H4K8, and H4K16 was accelerated, accompanied by an increase in HAT activity. OPA-induced increases in the mRNA expression of lipogenic genes were down-regulated by C-646, a p300/CBP-specific inhibitor. Finally, we detected a positive correlation between HAT activity and lipid accumulation (Pearson's correlation coefficient = 0.604) using 22 NExs. CONCLUSIONS: Our results suggest that NExs have novel applications as nutraceutical agents with HAT inhibitor activity for the prevention and treatment of NAFLD.


Subject(s)
Acetylation , Dietary Supplements , Epigenomics , Hep G2 Cells , Histone Acetyltransferases , Histones , Lipid Metabolism , Lipogenesis , Liver , Lysine , Metabolic Diseases , Non-alcoholic Fatty Liver Disease , RNA, Messenger , Sterol Regulatory Element Binding Protein 1
13.
Article in English | WPRIM | ID: wpr-760166

ABSTRACT

BACKGROUND/AIMS: Pancreatic cancer (PC) patients have poor prognoses because this cancer is typically diagnosed at an advanced stage and the therapeutic options are limited. We examined the potential of metabolic profiling for early diagnosis and identification of potential therapeutic targets. METHODS: Ten patients and 10 healthy volunteer controls older than 20 years of age were enrolled between May and December 2015. The patients were confirmed to have pancreatic ductal adenocarcinoma cytologically or histologically. Blood plasma samples were derivatized and analyzed by gas chromatography mass spectrometry (GC-MS). Untargeted GC-MS data were analyzed using statistical methods, including Wilcoxon rank-sum test and principal component analyses. RESULTS: L-lysine was 1.36-fold higher in patients than in healthy controls (p<0.05). L-leucine was 0.63-fold lower (p<0.01) and palmitic acid was 0.93-fold lower (p<0.5) in patients than in controls. Orthogonal partial least squared-discriminant analysis revealed significant differences between the patients and controls. CONCLUSIONS: This study suggests that the metabolic profiles of patients with PC are distinct from those of the healthy population. Further studies are required to develop methods for early diagnosis and identify therapeutic targets.


Subject(s)
Adenocarcinoma , Early Diagnosis , Gas Chromatography-Mass Spectrometry , Healthy Volunteers , Humans , Korea , Leucine , Lysine , Metabolome , Palmitic Acid , Pancreatic Ducts , Pancreatic Neoplasms , Plasma , Principal Component Analysis , Prognosis
14.
Immune Network ; : e9-2019.
Article in English | WPRIM | ID: wpr-740219

ABSTRACT

Staphylococcus aureus, a Gram-positive pathogen, can cause severe inflammation in humans, leading to various life-threatening diseases. The lipoprotein is a major virulence factor in S. aureus-induced infectious diseases and is responsible for excessive inflammatory mediators such as nitric oxide (NO). Short-chain fatty acids (SCFAs) including butyrate, propionate, and acetate are microbial metabolites in the gut that are known to have anti-inflammatory effects in the host. In this study, we investigated the effects of SCFAs on S. aureus lipoprotein (Sa.LPP)-induced NO production in mouse macrophages. Butyrate and propionate, but not acetate, inhibited Sa.LPP-induced production of NO in RAW 264.7 cells and bone marrow-derived macrophages. Butyrate and propionate inhibited Sa.LPP-induced expression of inducible NO synthase (iNOS). However, acetate did not show such effects under the same conditions. Furthermore, butyrate and propionate, but not acetate, inhibited Sa.LPP-induced activation of NF-κB, expression of IFN-β, and phosphorylation of STAT1, which are essential for inducing transcription of iNOS in macrophages. In addition, butyrate and propionate induced histone acetylation at lysine residues in the presence of Sa.LPP in RAW 264.7 cells. Moreover, Sa.LPP-induced NO production was decreased by histone deacetylase (HDAC) inhibitors. Collectively, these results suggest that butyrate and propionate ameliorate the inflammatory responses caused by S. aureus through the inhibition of NF-κB, IFN-β/STAT1, and HDAC, resulting in attenuated NO production in macrophages.


Subject(s)
Acetylation , Animals , Butyrates , Communicable Diseases , Diethylpropion , Fatty Acids, Volatile , Histone Deacetylase Inhibitors , Histone Deacetylases , Histones , Humans , Inflammation , Lipoproteins , Lysine , Macrophages , Mice , Nitric Oxide Synthase , Nitric Oxide , Phosphorylation , Staphylococcus aureus , Virulence
15.
Article in English | WPRIM | ID: wpr-739657

ABSTRACT

Mixed lineage leukemia proteins (MLL) are the key histone lysine methyltransferases that regulate expression of diverse genes. Aberrant activation of MLL promotes leukemia as well as solid tumors in humans, highlighting the urgent need for the development of an MLL inhibitor. We screened and isolated MLL1-binding ssRNAs using SELEX (Systemic Evolution of Ligands by Exponential enrichment) technology. When sequences in sub-libraries were obtained using next-generation sequencing (NGS), the most enriched aptamers—APT1 and APT2—represented about 30% and 26% of sub-library populations, respectively. Motif analysis of the top 50 sequences provided a highly conserved sequence: 5′-A[A/C][C/G][G/U][U/A]ACAGAGGG[U/A]GG[A/C] GAGUGGGU-3′. APT1, APT2, and APT5 embracing this motif generated secondary structures with similar topological characteristics. We found that APT1 and APT2 have a good binding activity and the analysis using mutated aptamer variants showed that the site information in the central region was critical for binding. In vitro enzyme activity assay showed that APT1 and APT2 had MLL1 inhibitory activity. Three-dimensional structure prediction of APT1-MLL1 complex indicates multiple weak interactions formed between MLL1 SET domain and APT1. Our study confirmed that NGS-assisted SELEX is an efficient tool for aptamer screening and that aptamers could be useful in diagnosis and treatment of MLL1-mediated diseases.


Subject(s)
Aptamers, Nucleotide , Conserved Sequence , Diagnosis , Histones , Humans , In Vitro Techniques , Leukemia , Ligands , Lysine , Mass Screening , Methyltransferases , Myeloid-Lymphoid Leukemia Protein , RNA
16.
Article in English | WPRIM | ID: wpr-739653

ABSTRACT

Suppressor of Variegation 3–9 Homolog 2 (SUV39H2) methylates the lysine 9 residue of histone H3 and induces heterochromatin formation, resulting in transcriptional repression or silencing of target genes. SUV39H1 and SUV39H2 have a role in embryonic development, and SUV39H1 was shown to suppress cell cycle progression associated with Rb. However, the function of human SUV39H2 has not been extensively studied. We observed that forced expression of SUV39H2 decreased cell proliferation by inducing G1 cell cycle arrest. In addition, SUV39H2 was degraded through the ubiquitin-proteasomal pathway. Using yeast two-hybrid screening to address the degradation mechanism and function of SUV39H2, we identified translationally controlled tumor protein (TCTP) as an SUV39H2-interacting molecule. Mapping of the interacting regions indicated that the N-terminal 60 amino acids (aa) of full-length SUV39H2 and the C-terminus of TCTP (120–172 aa) were critical for binding. The interaction of SUV39H2 and TCTP was further confirmed by co-immunoprecipitation and immunofluorescence staining for colocalization. Moreover, depletion of TCTP by RNAi led to up-regulation of SUV39H2 protein, while TCTP overexpression reduced SUV39H2 protein level. The half-life of SUV39H2 protein was significantly extended upon TCTP depletion. These results clearly indicate that TCTP negatively regulates the expression of SUV39H2 post-translationally. Furthermore, SUV39H2 induced apoptotic cell death in TCTP-knockdown cells. Taken together, we identified SUV39H2, as a novel target protein of TCTP and demonstrated that SUV39H2 regulates cell proliferation of lung cancer cells.


Subject(s)
Amino Acids , Apoptosis , Carrier Proteins , Cell Cycle , Cell Death , Cell Proliferation , Embryonic Development , Female , Fluorescent Antibody Technique , G1 Phase Cell Cycle Checkpoints , Half-Life , Heterochromatin , Histones , Humans , Immunoprecipitation , Lung Neoplasms , Lysine , Mass Screening , Pregnancy , Repression, Psychology , RNA Interference , Up-Regulation , Yeasts
17.
Article in Chinese | WPRIM | ID: wpr-775996

ABSTRACT

Leukemia is a disease featured by the malignant proliferation of hematopoietic stem cells or progenitor cells in the blood system.While chemotherapy remains its mainstream treatment,disease relapse and drug resistance are still challenging problems.As one of the epigenetic mechanisms,histone methylation is involved in cell proliferation,differentiation,and apoptosis by regulating gene transcription.Recent studies have found that the histone demethylase lysine-specific demethylase 6A(KDM6A),also known as ubiquitously transcribed tetratricopeptide repeat on chromosome X(UTX),is closely related to the occurrence of a variety of tumors,especially leukemia.KDM6A activates gene expression by demethylating H3K27me3 to H3K27me2 or H3K27me1.Besides,KDM6A can regulate the activation of the target gene transcription through its non-demethylase functions.It can serve as the subunit of complex of proteins associated with Set1,thus getting involved in the regulation of H3K4me1.It can be combined with yeast mating type conversion/sucrose unfermented complex family to promote the formation of an open chromatin conformation.Finally,it can promote the production of H3K27ac.This article reviews the recent studies on the structure and biological activity of histone demethylase KDM6A(UTX)and its role in treating leukemia,thus providing a new research direction for targeted treatment of leukemia.


Subject(s)
Epigenesis, Genetic , Histone Demethylases , Metabolism , Histones , Humans , Leukemia , Therapeutics , Lysine , Nuclear Proteins , Metabolism
18.
Chinese Journal of Biotechnology ; (12): 607-615, 2019.
Article in Chinese | WPRIM | ID: wpr-771348

ABSTRACT

Isopeptide bond-mediated molecular superglue is the irreversible covalent bond spontaneously formed by the side chains of lysine (Lys) and asparagine/aspartic acid (Asn/Asp) residues. The peptide-peptide interaction is specific, stable, and can be achieved quickly without any particular physicochemical factor. In the light of recent progress by domestic and foreign researchers, here we summarize the origin, assembly system and mechanism of isopeptide bond reaction, as well as the molecular cyclization and protein topological structure mediated by it. The prospect for its application in synthetic vaccine, hydrogel and bacterial nanobiological reactor is further discussed.


Subject(s)
Cyclization , Lysine , Peptides , Chemistry , Proteins
19.
Einstein (Säo Paulo) ; 17(2): eAO4576, 2019. tab, graf
Article in English | LILACS | ID: biblio-1001897

ABSTRACT

ABSTRACT Objective: To evaluate the effect of red propolis and L-lysine on angiogenesis and tumor growth in a new model of hamster cheek pouch inoculated with Walker 256 tumor cells. Methods: The study consisted of two experiments with four groups each (total: 57 hamsters). In the experiment 1, the animals were inoculated with Walker tumor cells, followed by administration of test substances (red propolis 200mg/5mL/kg or L-lysine 150mg/kg) or control substances (gum arabic 5mL/kg or water 5mL/kg) for 10 days. The animals in the experiment 2 received red propolis, L-lysine, gum arabic or water at the same doses, for 33 days prior to inoculation of Walker tumor cells, followed by 10 days of treatment with the same substances. Based on single-plane images, angiogenesis was quantified (mean vascular area), in percentage, and tumor area (mm2) and perimeter (mm). Results: In the experiment 1, compared to animals receiving water, the mean vascular area expressed in percentage was significantly smaller in animal treated with propolis (p<0.05) and L-lysine (p<0.001). Conclusion: Both red propolis and L-lysine inhibited tumor angiogenesis in the new hamster cheek pouch model when administered after tumor inoculation.


RESUMO Objetivo: Avaliar o efeito da própolis vermelha e da L-lisina na angiogênese e no crescimento tumoral em novo modelo de bolsa jugal de hamster inoculada com células de tumor de Walker 256. Métodos: O estudo consistiu em dois experimentos com quatro grupos cada (total: 57 hamsters). No experimento 1, os animais foram inoculados com células de tumor de Walker, tendo em seguida administradas as substâncias teste (própolis vermelha 200mg/5mL/kg ou L-lisina 150mg/kg) ou controle (goma arábica 5mL/kg ou água 5mL/kg) por 10 dias. Os animais do experimento 2 receberam própolis vermelha, L-lisina, goma arábica ou água nas mesmas doses, por 33 dias antes do inóculo das células de tumor de Walker, seguido por 10 dias de tratamento com as mesmas substâncias. Baseado em imagens em plano único, foram quantificados a angiogênese (área vascular média), em termos percentuais, e a área (mm2) e o perímetro (mm) do tumor. Resultados: Comparada aos animais que receberam água, a área vascular média, expressa em percentagem, foi significativamente menor nos animais tratados com própolis (p<0,05) e com L-lisina (p<0,001). Conclusão: Tanto a própolis vermelha quanto a L-lisina inibiram a angiogênese no novo modelo de bolsa jugal de hamsters, quando administradas após a inoculação do tumor.


Subject(s)
Propolis/therapeutic use , Angiogenesis Inhibitors/therapeutic use , Lysine/therapeutic use , Neovascularization, Pathologic/drug therapy , Mouth Neoplasms/chemically induced , Mouth Neoplasms/blood supply , Mouth Neoplasms/drug therapy , Carcinoma 256, Walker/blood supply , Weight Gain , Cheek , Cricetinae , Mesocricetus , Treatment Outcome , Models, Animal , Antioxidants
20.
Acta cir. bras ; 34(2): e201900207, 2019. tab, graf
Article in English | LILACS | ID: biblio-989054

ABSTRACT

Abstract Purpose: To evaluate red propolis, gum arabic and L-lysine activity on colorectal preneoplastic lesions induced by azoxymethane (AOM). Methods: The study featured 4 control groups (I-IV) and 4 experimental groups (V-VIII), totaling 48 rats. Once a week for 2 weeks, animals on control groups received saline, while animals in experimental groups received azoxymethane (15 mg/kg i.p.). The follow up along 16 weeks included daily oral gavage to administer water (I and V), L-lysine (150 mg/kg)(II and VI), própolis (100mg/5ml/kg)(III and VII), or gum arabic (5ml/kg)(IV and VIII). Was performed surgery on the animals in the end of this time in order to collect blood for biological assays (TBARS, GSH), followed by their sacrifice to tissue extract. Results: Oxidative stress (TBARS) and the number of aberrant crypt foci (ACF) in distal colon were lower using própolis (p<0.01 for both parameters). Gum arabic reduced preneoplastic lesions (ACF ≤ 4 crypts) on distal colon and on the entire colon (p<0.05). Conclusions: Red propolis reduced AOM-induced oxidative stress (TBARS) and total number of ACF in the distal colon. L-lysine neither protected against nor enhanced AOM-induced ACF. Gum arabic reduced the number of ACF.


Subject(s)
Animals , Male , Rats , Precancerous Conditions/prevention & control , Propolis/pharmacology , Colorectal Neoplasms/prevention & control , Oxidative Stress/drug effects , Gum Arabic/pharmacology , Lysine/pharmacology , Precancerous Conditions/chemically induced , Azoxymethane , Carcinogens , Colorectal Neoplasms/chemically induced , Rats, Wistar , Disease Models, Animal
SELECTION OF CITATIONS
SEARCH DETAIL