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1.
Trop Anim Health Prod ; 54(1): 61, 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35037142

RESUMO

The objective of this study was to investigate the effects of rumen-protected lysine (RPL) and methionine (RPM) supplementation on production performance of nursing ewes fed two levels of dietary protein. Individually housed Awassi ewes (n = 34) nursing single lambs were randomly assigned (2 × 2 factorial design) to one of four dietary treatments with two levels of protein (170 or 151 g/kg; HP or MP) and two levels of RPL and RPM (0 or 8.5 plus 4 g/day/ewe of RPL and RPM, respectively; no or yes). The trial lasted for 5 weeks. Ewes fed the MP diets had (P < 0.01) lower protein intake compared to those fed the HP diets. Intake of other nutrients and milk composition were not significantly (P > 0.13) affected by dietary treatments. Ewes fed the MPYES diet produced more (P < 0.05) milk compared to those fed the MPNO and HPYES diets and tended (P = 0.08) to be more than the HPNO diet. Additionally, milk composition yields for the MPYES diet were significantly (P < 0.05) more than the HPYES diets and tended (P ≤ 0.10) to be more than the MPNO and HPNO diets. Milk efficiency was highest (P < 0.05) for the MPYES diet. Final BW, total gain, and growth rate of lambs were greater when their dams were fed the MPYES diet compared to MPNO and HPNO diets. Under our conditions, decreasing dietary protein from 170 to 151 g/kg did not negatively affect the performance of ewes and their lambs. Supplemental RPL and RPM were beneficial for ewes fed diets containing 151 g/kg, but not 170, protein.


Assuntos
Lisina , Metionina , Ração Animal/análise , Animais , Dieta/veterinária , Proteínas na Dieta , Suplementos Nutricionais , Feminino , Lactação , Leite , Rúmen , Ovinos , Carneiro Doméstico
2.
Chem Phys Lipids ; 242: 105164, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34906552

RESUMO

The selection of an animal model is based on the pathological mechanism appropriate for experimental investigation because the therapeutic effect was low depending on the pathological occurrence mechanism. The purpose of this study is to elucidate the changes in lipid proton concentration in two animal models of nonalcoholic fatty liver disease (NAFLD): methionine and choline-deficient (MCD) diet and high-fat diet (HFD). We calculated the T2 relaxation time of 7 lipid protons (LP) in the 9.4 T MRS phantom experiment. The concentrations of LPs were adjusted for T2 and T2* of MCD, HFD, and CCl4 fatty liver animal models. Multivariate analysis and Pearson correlation were performed to analyze LP concentration, and the difference was investigated via Kendall correlation and independent t-test using LP composition ratio. The T2 relaxation time of each LP was accurately determined using phantom experiments. The in vivo magnetic resonance spectroscopy (MRS) data were obtained by quantifying the t2/t2* corrected LP concentration in the liver of the animal model. In case of MCD and HFD, there was an average difference in all LPs except 0.9 ppm LP, and the MCD and CCl4 groups showed differences in the average of all LPs. However, there was no difference between LP of HFD and CCl4 groups. A higher level of unsaturated fatty acids was found in the MCD fatty liver model than in HFD induced fatty liver.


Assuntos
Metionina , Hepatopatia Gordurosa não Alcoólica , Animais , Colina , Dieta Hiperlipídica , Modelos Animais de Doenças , Lipídeos , Fígado/diagnóstico por imagem , Imageamento por Ressonância Magnética , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Prótons
3.
Biol Trace Elem Res ; 200(1): 156-163, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33590455

RESUMO

This study aimed to investigate the effect of dietary high doses of chromium-methionine (CrMet) supplementation on blood hemato-biochemical parameters and growth performance of finishing lambs reared under warm condition with average temperature-humidity index (THI) of 85.8 unit. Fifteen male lambs (31.9 ± 1.2 kg) fed with either un-supplemented diet (CON) or supplemented with 1.5 (Cr1.5) and 3 (Cr3) mg of Cr/kg dry matter (DM) for 8 weeks. The results showed that high levels of supplemental Cr had no negative impacts on red (RBC) and white blood cells (WBC). Blood total antioxidant capacity (TAOC) tended to be higher in CrMet-fed lambs than those of CON (P < 0.1). Serum malondialdehyde (MDA), as a lipid peroxidation marker, was, respectively, 20.24 and 22.1%, lower in lambs given 1.5 and 3 mg of chromium comparing those of CON (P < 0.05). Moreover, erythrocyte glutathione peroxidase (GSH-PX, U/dL) displayed higher activity in Cr3 (421.2) group than those of CON (334.6) and Cr1.5 (351.2) groups (P < 0.05). Accordingly, GSH-PX activity per gram hemoglobin (U/gHb) was 45.9% greater in lambs of Cr3 than the CON (P < 0.05). Furthermore, feeding 3 mg of Cr led to increased erythrocyte superoxide dismutase (SOD) activity (P < 0.05): as such, SOD was 1193.1, 1281.5, and 1433.0 U/gHb in CON, Cr1.5, and Cr3, respectively. Chromium supplementation linearly decreased serum iron concentration (P < 0.05), but neither blood calcium, phosphorous, copper, zinc, and glucose concentrations nor aspartate aminotransferase and alanine aminotransferase activities were affected by supplemental CrMet. In comparison with CON (1250), lambs in Cr1.5 (1199) and Cr3 (1192) groups had lower daily feed intake (g/d, P < 0.01). In addition, feed to gain ratio was 21.5% lower in the Cr3 group than the control (P < 0.05). Collectively, these findings suggest that feeding summer-exposed finishing lambs with 3 mg of Cr/kg DM improves blood antioxidant status and feed to gain efficiency without adverse effects on lambs' health and metabolism.


Assuntos
Antioxidantes , Metionina , Ração Animal/análise , Animais , Células Sanguíneas , Cromo/farmacologia , Dieta , Suplementos Nutricionais , Ingestão de Alimentos , Masculino , Minerais , Ovinos
4.
Clin Nucl Med ; 47(1): e66-e67, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34284472

RESUMO

ABSTRACT: A 33-year-old nursing mother who underwent resection of a glioblastoma of the right hemisphere was referred for a 11C-methionine PET/MR scan to exclude cancer recurrence. In whole-body PET imaging, a slight radiotracer uptake could be observed in the mammary glands, reflecting lactation status. In this case report, we initially describe 11C-methionine uptake in the human breast and discuss any consequences arising from this special situation.


Assuntos
Lactação , Recidiva Local de Neoplasia , Adulto , Radioisótopos de Carbono , Feminino , Humanos , Metionina
5.
Food Chem ; 372: 131281, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-34655832

RESUMO

The mechanism responsible for the appearance of the light-struck fault upon exposure of white wines and Champagnes to natural or artificial light is examined in light of new experiments involving methionine analogues. The latter show that the formation of volatile sulfur species upon irradiation of riboflavin in the presence of methionine in model wine solutions at pH 3 is not dependent on the existence of neighboring group stabilization of the sulfur-centered cation radical through a 5- or 6-membered cyclic intermediate. Instead, the formation of a dimer radical cation is proposed in agreement with the formation of oxidation products such as dimethyl disulfide at early reaction times and the observed steric effect upon product distribution. The limiting quantum yield for the release of sulfur atoms from a solution of methionine in model wine solutions at pH 3.5 containing riboflavin was found to be 0.26 (435 nm irradiation). No dependence of the quantum yield or product distribution on the irradiation wavelength was found over the range 365-90 nm.


Assuntos
Vinho , Aromatizantes , Metionina , Oxirredução , Paladar , Vinho/análise
6.
Nutrients ; 13(12)2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34960114

RESUMO

The 5-10-methylenetetrahydrofolate reductase (MTHFR) enzyme is vital for cellular homeostasis due to its key functions in the one-carbon cycle, which include methionine and folate metabolism and protein, DNA, and RNA synthesis. The enzyme is responsible for maintaining methionine and homocysteine (Hcy) balance to prevent cellular dysfunction. Polymorphisms in the MTHFR gene, especially C677T, have been associated with various diseases, including cardiovascular diseases (CVDs), cancer, inflammatory conditions, diabetes, and vascular disorders. The C677T MTHFR polymorphism is thought to be the most common cause of elevated Hcy levels, which is considered an independent risk factor for CVD. This polymorphism results in an amino acid change from alanine to valine, which prevents optimal functioning of the enzyme at temperatures above 37 °C. Many studies have been conducted to determine whether there is an association between the C677T polymorphism and increased risk for CVD. There is much evidence in favour of this association, while several studies have concluded that the polymorphism cannot be used to predict CVD development or progression. This review discusses current research regarding the C677T polymorphism and its relationship with CVD, inflammation, diabetes, and epigenetic regulation and compares the evidence provided for and against the association with CVD.


Assuntos
Doenças Cardiovasculares/epidemiologia , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Polimorfismo Genético , Ciclo do Carbono , Diabetes Mellitus/epidemiologia , Epigênese Genética , Feminino , Ácido Fólico/metabolismo , Fatores de Risco de Doenças Cardíacas , Homocisteína/metabolismo , Humanos , Inflamação/epidemiologia , Masculino , Metionina/metabolismo , Doenças Vasculares/epidemiologia , Vitamina B 12/metabolismo
7.
Int J Mol Sci ; 22(24)2021 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-34948174

RESUMO

Methionine restriction reduces animal lipid deposition. However, the molecular mechanism underlying how the body reacts to the condition and regulates lipid metabolism remains unknown. In this study, a feeding trial was performed on rice field eel Monopterus albus with six isonitrogenous and isoenergetic feeds that included different levels of methionine (0, 2, 4, 6, 8, and 10 g/kg). Compared with M0 (0 g/kg), the crude lipid and crude protein of M. albus increased markedly in M8 (8 g/kg) (p < 0.05), serum (total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and non-esterified free fatty acids), and hepatic contents (hepatic lipase, apolipoprotein-A, fatty acid synthetase, total cholesterol, triglyceride, and lipoprteinlipase). However, in the serum, very-low-density lipoprotein and hepatic contents (hormone-sensitive triglyceride lipase, Acetyl CoA carboxylase, carnitine palmitoyltransterase, and mirosomal triglygeride transfer protein) decreased markedly in M8 (p < 0.05). The contents of hepatic C18:2n-6, C22:6n-3, and n-3PUFA in the M8 group were significantly higher than those in M0 (p < 0.05), and the contents of lipid droplets in M8 were higher than those in M0. Compared with M0, the hepatic gcn2, eif2α, hsl, mttp, ldlrap, pparα, cpt1, and cpt2 were remarkably downregulated in M8, while srebf2, lpl, moat2, dgat2, hdlbp, srebf1, fas, fads2, me1, pfae, and icdh were markedly upregulated in M8. Moreover, hepatic SREBP1 and FAS protein expression were upregulated significantly in M8 (p < 0.01). In short, methionine restriction decreased the lipid deposition of M. albus, especially for hepatic lipid deposition, and mainly downregulated hepatic fatty acid metabolism. Besides, gcn2 could be activated under methionine restriction.


Assuntos
Metabolismo dos Lipídeos/efeitos dos fármacos , Metionina/farmacologia , Smegmamorpha/metabolismo , Acetil-CoA Carboxilase/metabolismo , Animais , China , Dieta , Suplementos Nutricionais , Ácidos Graxos/metabolismo , Fígado Gorduroso/metabolismo , Metabolismo dos Lipídeos/fisiologia , Lipídeos/fisiologia , Lipoproteínas VLDL/metabolismo , Fígado/metabolismo , Metionina/deficiência , Metionina/metabolismo , RNA Mensageiro/metabolismo , Esterol Esterase/metabolismo , Triglicerídeos/metabolismo
8.
J Coll Physicians Surg Pak ; 31(12): 1445-1448, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34794285

RESUMO

OBJECTIVE: To compare the effect of ursodesoxycholic acid (UDCA) with S-adenosyl-L-methionine (SAMe) plus UDCA in handling of cholestasis in neonates, and their influences on serum endotoxin, matrix metalloproteinase-9 (MMP-9) and interleukin 18 (IL-18). STUDY DESIGN: Randomised controlled trial. PLACE AND DURATION OF STUDY:  Luzhou People's Hospital, China, from April 2019 to December 2020. METHODOLOGY: A total of 102 neonates with cholestasis were evenly divided into control group and observation group with random double-blind. The former treated with UDCA tablets, and the latter was treated with SAMe plus UDCA. Serum endotoxin, MMP-9 and IL-18 were compared between the two groups. RESULTS: Total effective rate of treatment in observation group was 92.16% (47 cases), which was higher than that in control group 70.59% (36 cases) (p=0.005). Levels of serum endotoxin, MMP-9 and IL-18 in observation group were respectively 11.12 ± 1.07 pg/mL, 646.72 ± 42.56 ng/mL and 2.51 ± 0.19 pg/mL, which was lower than those in control group (p<0.001, p =0.007 and p<0.001, respectively) after 10 days of treatment. CONCLUSION: Compared with UDCA alone, SAMe plus UDCA can more effectively improve the curative effect of neonatal cholestasis, and reduce serum endotoxin, MMP-9 and IL-18 levels. Key Words: Ursodesoxycholic acid (UDCA), Neonates, Cholestasis, Endotoxin, Matrix metalloproteinase-9 (MMP-9), Interleukin 18 (IL-18).


Assuntos
Colestase Intra-Hepática , Colestase , Complicações na Gravidez , Colestase/tratamento farmacológico , Endotoxinas , Feminino , Humanos , Recém-Nascido , Interleucina-18 , Metaloproteinase 9 da Matriz , Metionina , Gravidez , S-Adenosilmetionina , Ácido Ursodesoxicólico
9.
BMC Genomics ; 22(1): 780, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34717556

RESUMO

BACKGROUND: The evaluation of alternative splicing, including differential isoform expression and differential exon usage, can provide some insights on the transcriptional changes that occur in response to environmental perturbations. Maternal nutrition is considered a major intrauterine regulator of fetal developmental programming. The objective of this study was to assess potential changes in splicing events in the longissimus dorsi muscle of beef calves gestated under control or methionine-rich diets. RNA sequencing and whole-genome bisulfite sequencing were used to evaluate muscle transcriptome and methylome, respectively. RESULTS: Alternative splicing patterns were significantly altered by maternal methionine supplementation. Most of the altered genes were directly implicated in muscle development, muscle physiology, ATP activities, RNA splicing and DNA methylation, among other functions. Interestingly, there was a significant association between DNA methylation and differential exon usage. Indeed, among the set of genes that showed differential exon usage, significant differences in methylation level were detected between significant and non-significant exons, and between contiguous and non-contiguous introns to significant exons. CONCLUSIONS: Overall, our findings provide evidence that a prenatal diet rich in methyl donors can significantly alter the offspring transcriptome, including changes in isoform expression and exon usage, and some of these changes are mediated by changes in DNA methylation.


Assuntos
Metilação de DNA , Metionina , Processamento Alternativo , Animais , Bovinos , Suplementos Nutricionais , Feminino , Metionina/metabolismo , Músculo Esquelético/metabolismo , Gravidez
10.
Appl Microbiol Biotechnol ; 105(21-22): 8393-8410, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34617138

RESUMO

Feeding low-protein (LP) diets with essential amino acids could be an effective strategy for ruminants from economic, health and environmental perspectives. This study was conducted to investigate the effects of rumen-protected methionine and lysine (RML) in the LP diet on growth performance, innate immunity, and gut health of growing lambs. After 15 days of adaption, sixty-three male Hulunbuir lambs aged approximately 4 months were allotted to three dietary groups and each group had three pens with seven lambs for 60 days. The dietary treatments were as follows: a normal protein diet (14.5% CP, positive control; NP), LP diet (12.5% CP, negative control; LP), and LP diet with RML (12.5% CP, LP + RML). Lambs fed with LP + RML diet showed improved villus architecture and gut barrier function than those fed with the other two diets. The mRNA expressions of interleukin-1ß, tumor necrosis factor-α, interferon-γ, toll-like receptor-4, and myeloid differentiation primary response 88 were downregulated in most regions of the intestinal segments by feeding the LP + RML diet. Compared with the NP diet, feeding lambs with the LP diet increased the abundance of Candidatus_Saccharimonas in all regions of the intestinal tract and reversed by feeding the LP + RML diet. Lambs in the LP + RML diet group had lower abundance of Erysipelotrichaceae_UCG-009 and Clostridium_sensu_stricto_1 than those in the LP diet group. The results showed that supplementing RML in the LP diet exhibited beneficial effects on host immune function, intestinal mucosal integrity, and microbiota composition. KEY POINTS: • Adding methionine and lysine in a low-protein diet improve the intestinal mucosal growth and integrity. • Feeding a low-protein diet with methionine and lysine enhance the innate immune status. • Adding methionine and lysine in a low-protein diet alter the intestinal microbiota composition.


Assuntos
Dieta com Restrição de Proteínas , Microbioma Gastrointestinal , Ração Animal/análise , Animais , Lisina , Masculino , Metionina , Ovinos
11.
Food Res Int ; 149: 110682, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34600684

RESUMO

Cow's milk is a highly-nutritious dairy product part of human diet worldwide. Rumen-protected methionine (RPM) is widely used to improve lactation performance of dairy cows, but understanding of the effects of RPM on milk nutrients composition are still limited. In this study, twenty mid-lactating dairy cows were supplemented with 20 gm/day RPM for 8 weeks to investigate the responses of milk nutritional composition to RPM. Metabolomics was applied for analyzing milk metabolites and 16S rRNA gene sequencing was used for analysis of rumen microbial composition. Milk fat content and yield were significantly increased after RPM supplementation. Totally 443 compounds belonging to 15 classes were identified, among which 15 metabolites were significantly changed. The functional nutrient α-ketoglutaric acid were significantly increased in the milk after RPM supplementation. We found 48 significantly differing bacterial genera in the rumen after supplementing RPM. Multi-omics integrated analysis revealed the higher abundance of Acetobacter, unclassified_f_Lachnospiraceae and Saccharofermentan contributed to the improved milk fat. In addition, the enriched abundance of Thermoactinomyces, Asteroleplasma, and Saccharofermentan showed positive correlations with higher α-ketoglutaric acid of milk. Our results uncover the metabolomic fingerprint and the key functional metabolites in the milk after supplementing RPM in dairy cows, as well as the key rumen bacteria associated with them. These findings provide novel insights into the development of functional dairy products that enriched the functional nutrient α-ketoglutaric acid or high milk fat.


Assuntos
Leite , Rúmen , Ração Animal/análise , Animais , Bovinos , Feminino , Humanos , Lactação , Metionina , Nutrientes , RNA Ribossômico 16S
12.
Animal ; 15(11): 100366, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34601210

RESUMO

The objective of this study was to evaluate the effect of supplementing a CP-reduced diet with rumen-protected methionine on growth performance of Fleckvieh bulls. A total of 69 bulls (367 ±â€¯25 kg BW) were assigned to three feeding groups (n = 23 per group). The control (CON) diet contained 13.7% CP and 2.11 g methionine/kg diet (both DM basis) and was set as positive control. The diet reduced in CP (nitrogen) (RED) diet as negative control and the experimental RED + rumen-protected methionine (MET) diet were characterised by deficient CP concentrations (both 9.04% CP). The RED + MET diet differed from the RED diet in methionine concentration (2.54 g/kg DM vs. 1.56 g/kg DM, respectively) due to supplementation of rumen-protected methionine. Rumen-protected lysine was added to both RED and RED + MET at 2.7 g/kg DM to ensure a sufficient lysine supply relative to total and metabolisable protein intake. Metabolisable energy (ME) and nutrient composition were similar for CON, RED, and RED + MET. Bulls were fed for 105 days (d) on average. Individual feed intake was recorded daily; individual BW was recorded at the beginning of the experiment, once per month, and directly before slaughter. At slaughter, blood samples were collected and carcass traits were assessed. Reduction in dietary CP concentration reduced feed intake, and in combination with lower dietary CP concentration, daily intake of CP for RED and RED + MET was lower compared with CON (P < 0.01). Daily ME intake was reduced in RED and RED + MET compared with CON (P < 0.01). Consequently growth performance and carcass weights were reduced (both P < 0.01) in both RED and RED + MET compared with CON. Supplemental rumen-protected methionine was reflected in increased serum methionine concentration in RED + MET (P < 0.05) as compared to RED but it did not affect growth performance, carcass traits and serum amino acid (AA) concentrations, except for lysine which was reduced (P < 0.01) compared to CON and RED. In conclusion, bulls fed RED or RED + MET diets were exposed to a ruminal CP deficit and subsequently a deficit of prececal digestible protein, but methionine did not appear to be the first-limiting essential AA for growth under the respective experimental conditions.


Assuntos
Metionina , Rúmen , Ração Animal/análise , Animais , Bovinos , Dieta/veterinária , Proteínas na Dieta , Suplementos Nutricionais , Masculino
13.
Nutrients ; 13(10)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34684455

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases with no approved treatment. Zonarol, an extract from brown algae, has been proven to have anti-inflammatory and antioxidant effects. In this study, we investigated the role of zonarol in the progression of methionine- and choline-deficiency (MCD) diet-induced NAFLD in mice. After oral treatment with zonarol, a lighter body weight was observed in zonarol group (ZG) mice in comparison to control group (CG) mice. The NAFLD scores of ZG mice were lower than those of CG mice. Hepatic and serum lipid levels were also lower in ZG mice with the reduced expression of lipid metabolism-related factors. Furthermore, ZG mice showed less lipid deposition, less inflammatory cell infiltration and lower inflammatory cytokine levels in comparison to CG mice. Moreover, the numbers of 8-hydroxy-20-deoxyguanosine (8-OHdG)-positive hepatocytes and levels of hepatic and serum thiobarbituric acid reactive substances (TBARS) were significantly lower in comparison to CG mice. The expression levels of nuclear factor erythroid 2 related factor 2 (Nrf2), as well as its upstream and downstream molecules, changed in ZG mice. Zonarol could prevent the progression of NAFLD by decreasing inflammatory responses, oxidative stress and improving lipid metabolism. Meanwhile the Nrf2 pathway may play an important role in these effects.


Assuntos
Deficiência de Colina/complicações , Dieta , Metionina/deficiência , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Substâncias Protetoras/farmacologia , Sesquiterpenos/farmacologia , Animais , Biomarcadores , Dieta/efeitos adversos , Modelos Animais de Doenças , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Imuno-Histoquímica , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Modelos Biológicos , Fator 2 Relacionado a NF-E2/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais
14.
Proteomics ; 21(20): e2100007, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34482643

RESUMO

Methionine (Met) and cystine (CySS) are key sulfur donors in cell metabolism and are important nutrients for sustaining tumor growth; however, the molecular effects associated with their deprivation remain to be characterized. Here, we applied a xenograft mouse model to assess the impact of their deprivation on A549 xenografts and the xenograft-bearing animal. Results show that Met and CySS deprivation inhibits A549 growth in vitro, not in vivo. Deprivation was detrimental to the xenograft-bearing mouse, as demonstrated by weight loss and renal dysfunction. Differentially expressed proteins in A549 xenograft and mouse kidneys were characterized using quantitative proteomics. Functional annotation and protein-protein interaction network analysis revealed the enriched signaling pathways, including focal adhesion (Fn1) in the A549 xenograft, and xenobiotic metabolism (Cyp2e1) and glutathione metabolism (Ggt1) in the mouse kidney. Met and CySS deprivation inhibits the migratory and invasive properties of cancer cells, as evidenced by reduced expression of the epithelial to mesenchymal transition marker N-cadherin in A549 cells in vitro. Moreover, IGFBP1 protein expression was inhibited in both A549 xenograft and mouse kidneys. This study provides the first insights into changes within the proteome profile and biological processes upon Met and CySS deprivation in a A549 xenograft mouse model.


Assuntos
Cistina , Neoplasias Pulmonares , Animais , Transição Epitelial-Mesenquimal , Xenoenxertos , Metionina , Camundongos , Proteômica
15.
Molecules ; 26(17)2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34500777

RESUMO

Human neutrophil elastase (HNE) is a uniquely destructive serine protease with the ability to unleash a wave of proteolytic activity by destroying the inhibitors of other proteases. Although this phenomenon forms an important part of the innate immune response to invading pathogens, it is responsible for the collateral host tissue damage observed in chronic conditions such as chronic obstructive pulmonary disease (COPD), and in more acute disorders such as the lung injuries associated with COVID-19 infection. Previously, a combinatorially selected activity-based probe revealed an unexpected substrate preference for oxidised methionine, which suggests a link to oxidative pathogen clearance by neutrophils. Here we use oxidised model substrates and inhibitors to confirm this observation and to show that neutrophil elastase is specifically selective for the di-oxygenated methionine sulfone rather than the mono-oxygenated methionine sulfoxide. We also posit a critical role for ordered solvent in the mechanism of HNE discrimination between the two oxidised forms methionine residue. Preference for the sulfone form of oxidised methionine is especially significant. While both host and pathogens have the ability to reduce methionine sulfoxide back to methionine, a biological pathway to reduce methionine sulfone is not known. Taken together, these data suggest that the oxidative activity of neutrophils may create rapidly cleaved elastase "super substrates" that directly damage tissue, while initiating a cycle of neutrophil oxidation that increases elastase tissue damage and further neutrophil recruitment.


Assuntos
Imunidade Inata , Elastase de Leucócito/metabolismo , Metionina/análogos & derivados , Neutrófilos/imunologia , Biocatálise , COVID-19/imunologia , COVID-19/patologia , COVID-19/virologia , Domínio Catalítico/genética , Ensaios Enzimáticos , Interações Hospedeiro-Patógeno/imunologia , Humanos , Elastase de Leucócito/antagonistas & inibidores , Elastase de Leucócito/genética , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Metionina/metabolismo , Simulação de Dinâmica Molecular , Infiltração de Neutrófilos , Neutrófilos/enzimologia , Oxirredução/efeitos dos fármacos , Proteólise/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/imunologia , Doença Pulmonar Obstrutiva Crônica/patologia , SARS-CoV-2/imunologia , Especificidade por Substrato/imunologia
16.
Clin Neurophysiol ; 132(11): 2827-2839, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34592560

RESUMO

OBJECTIVE: While previous studies showed that the single nucleotide polymorphism (Val66Met) of brain-derived neurotrophic factor (BDNF) can impact neuroplasticity, the influence of BDNF genotype on cortical circuitry and relationship to neuroplasticity remain relatively unexplored in human. METHODS: Using individualised transcranial magnetic stimulation (TMS) parameters, we explored the influence of the BDNF Val66Met polymorphism on excitatory and inhibitory neural circuitry, its relation to I-wave TMS (ITMS) plasticity and effect on the excitatory/inhibitory (E/I) balance in 18 healthy individuals. RESULTS: Excitatory and inhibitory indexes of neurotransmission were reduced in Met allele carriers. An E/I balance was evident, which was influenced by BDNF with higher E/I ratios in Val/Val homozygotes. Both long-term potentiation (LTP-) and depression (LTD-) like ITMS plasticity were greater in Val/Val homozygotes. LTP- but not LTD-like effects were restored in Met allele carriers by increasing stimulus intensity to compensate for reduced excitatory transmission. CONCLUSIONS: The influence of BDNF genotype may extend beyond neuroplasticity to neurotransmission. The E/I balance was evident in human motor cortex, modulated by BDNF and measurable using TMS. Given the limited sample, these preliminary findings warrant further investigation. SIGNIFICANCE: These novel findings suggest a broader role of BDNF genotype on neurocircuitry in human motor cortex.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Potenciais Pós-Sinápticos Excitadores/fisiologia , Potenciais Pós-Sinápticos Inibidores/fisiologia , Córtex Motor/fisiologia , Plasticidade Neuronal/fisiologia , Polimorfismo de Nucleotídeo Único/genética , Adulto , Eletromiografia/métodos , Potencial Evocado Motor/fisiologia , Feminino , Humanos , Masculino , Metionina/genética , Estimulação Magnética Transcraniana/métodos , Valina/genética
17.
Methods Enzymol ; 658: 161-190, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34517946

RESUMO

The RNA methyltransferase (MTase) complex METTL3-METTL14 transfers methyl groups from S-adenosyl-l-methionine (AdoMet) to the N6-position of adenosines within its consensus sequence, the DRACH motif (D=A, G, U; R=A, G; H=A, C, U). Interestingly, this MTase complex shows remarkable promiscuity regarding the cosubstrate. This can be exploited to install nonnatural modifications, like clickable or photocaging groups. Clickable groups are widely used for subsequent functionalization and open a broad range of possibilities for downstream applications. Here, we elaborate on click chemistry for coupling of RNA to biotin to enrich MTase targets via streptavidin-coated magnetic beads. Importantly, after clicking and coupling to beads the modification becomes sterically demanding and stalls reverse transcriptases, leading to termination adjacent to the MTase target site. Using radioactively labeled primers in the reverse transcription, the modified position can be precisely identified on a sequencing gel via phosphor imaging.


Assuntos
Metiltransferases , RNA , Adenosina , Metionina , Metiltransferases/genética , S-Adenosilmetionina
18.
Nat Commun ; 12(1): 5416, 2021 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-34518544

RESUMO

Hypoxia is the most prominent feature in human solid tumors and induces activation of hypoxia-inducible factors and their downstream genes to promote cancer progression. However, whether and how hypoxia regulates overall mRNA homeostasis is unclear. Here we show that hypoxia inhibits global-mRNA decay in cancer cells. Mechanistically, hypoxia induces the interaction of AGO2 with LUBAC, the linear ubiquitin chain assembly complex, which co-localizes with miRNA-induced silencing complex and in turn catalyzes AGO2 occurring Met1-linked linear ubiquitination (M1-Ubi). A series of biochemical experiments reveal that M1-Ubi of AGO2 restrains miRNA-mediated gene silencing. Moreover, combination analyses of the AGO2-associated mRNA transcriptome by RIP-Seq and the mRNA transcriptome by RNA-Seq confirm that AGO2 M1-Ubi interferes miRNA-targeted mRNA recruiting to AGO2, and thereby facilitates accumulation of global mRNAs. By this mechanism, short-term hypoxia may protect overall mRNAs and enhances stress tolerance, whereas long-term hypoxia in tumor cells results in seriously changing the entire gene expression profile to drive cell malignant evolution.


Assuntos
Proteínas Argonauta/genética , Regulação Neoplásica da Expressão Gênica , Homeostase/genética , Metionina/genética , RNA Mensageiro/genética , Ubiquitinação , Células A549 , Proteínas Argonauta/metabolismo , Hipóxia Celular , Linhagem Celular Tumoral , Inativação Gênica , Células HEK293 , Células HeLa , Humanos , Hipóxia , Metionina/metabolismo , MicroRNAs/genética , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Células PC-3 , Estabilidade de RNA/genética , RNA Mensageiro/metabolismo
19.
Se Pu ; 39(10): 1118-1127, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34505434

RESUMO

The late endosomal/lysosomal adaptor MAPK and mTOR activator 1 (LAMTOR1) is an important regulator protein in the response to energy stress. Public gene expression data shows that the expression of LAMTOR1 is abnormally high in nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC); hence, LAMTOR1 may play an important role in the development of NASH and HCC. Therefore, exploring the LAMTOR1 regulatory mechanism in the progression of NASH and malignant transformation of liver inflammation may be crucial for translational medicine. First, a NASH mouse model was established by feeding a methionine choline-deficient (MCD) diet. Hematoxylin-eosin staining of liver tissues showed successful modeling of inflammatory injury in the mouse liver. Immunoblot analysis confirmed LAMTOR1- and LAMTOR1-mediated protein expression in LAMTOR1 specifically depleted mouse livers. Subsequently, metabolic profiling of liver tissues was performed using an ultra-performance liquid chromatography-time-of-flight mass spectrometry strategy. Based on the retention time, m/z value, and tandem mass spectra, 134 metabolites were identified. Among these, the levels of 45 metabolite were significantly influenced by hepatic LAMTOR1 depletion. According to the metabolomics results, uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) was significantly upregulated in LAMTOR1-depleted (LAMTOR1LKO) hepatocyte tissues. As the final product of the hexosamine biosynthetic pathway (HBP), alteration in UDP-GlcNAc levels may regulate LAMTOR1 and metabolic regulatory genes downstream of HBP. Moreover, there was an obvious increase in the levels of several methylation-related metabolites. Thus, upregulated S-adenosylmethionine, S-adenosylhomocysteine, and N6,N6,N6-trimethyl-L-lysine indicated that LAMTOR1 may regulate the process of DNA or protein methylation. In addition, downregulation of 9-oxo-octadecadienoate, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) was also observed in LAMTOR1LKO mice liver tissues. Alterations in polyunsaturated fatty acids, such as EPA and DHA, link LAMTOR1 to inflammatory and immune processes, which are known to play important roles in NASH pathogenesis. These metabolic disorders demonstrated that LAMTOR1 significantly contributed to the metabolic mechanism of NASH. Furthermore, gene expression correlations were analyzed to interpret the regulatory role of LAMTOR1 from the perspective of genetic networks. Owing to a paucity of liver whole-transcriptome studies in NASH, correlation analysis was performed based on HCC transcriptome data from public databases. First, a negatively regulated relationship was observed between LAMTOR1 and MAT1A (R=-0.47). MAT1A encodes methionine adenosyltransferase 1A, an essential enzyme that catalyzes the formation of S-adenosylmethionine. Based on the upregulation of UDP-GlcNAc under hepatocyte LAMTOR1 depletion, it was predicted that LAMTOR1 positively influenced MGAT1 (R=0.47), a gene encoding alpha-1,3-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase. Together with changes in succinyladenosine caused by hepatocyte LAMTOR1 deletion, predicted correlation results showed that LAMTOR1 may also participate in the pathogenesis through the positive regulatory relationship with ADSL (R=0.59). The ADSL gene provides instructions for making an enzyme called adenylosuccinate lyase, which can dephosphorylate the substrate succinyladenosine. In this study, LAMTOR1 was identified to specifically regulate multiple key metabolic pathways based on both NASH mouse models and gene expression correlations. These results illustrate the important role of LAMTOR1 in the progression of NASH and malignant transformation of liver inflammation, which provides a theoretical basis for the diagnosis and treatment of NASH or possible NASH-driven HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Cromatografia Líquida , Modelos Animais de Doenças , Inflamação , Fígado , Espectrometria de Massas , Metionina , Camundongos
20.
Poult Sci ; 100(11): 101427, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34551373

RESUMO

The study was conducted to evaluate the effects of low crude protein diets supplemented with arginine, glutamine, methionine, and/or threonine on apparent ileal digestibility of amino acids, intestinal morphology, intestinal permeability, gene expression of nutrient transporters, and tight junction proteins of broiler chickens challenged with mixed Eimeria spp. A total of five hundred seventy-six, 12-day-old male broiler chickens were allocated into 8 treatments, and 6 replicate cages of 12 chickens per cage. This experiment included a nonchallenged control (NC) fed regular corn-soybean meal-based diet (Regular diet, 19% crude protein), an Eimeria-challenged control (CC) fed Regular diet, an Eimeria challenge group fed low-crude protein diet (LCP, 16% crude protein), 4 Eimeria challenge groups fed low-crude protein diet supplemented with 0.75% arginine, glutamine, methionine, and threonine, respectively (ARG, GLN, MET, and THR), and an Eimeria challenge group fed low-crude protein diet with 0.75% supplemented arginine, glutamine, methionine, and threonine collectively as a combination group (COMB). On d 14, birds in the challenge groups were gavaged with a mixed Eimeria spp. solution containing 12,500 oocysts of E. maxima, 12,500 oocysts of E. tenella, and 62,500 oocysts of E. acervulina. The results showed that the Eimeria challenge reduced overall growth performance, but the LCP had no adverse impacts on intestinal health and growth of Eimeria-infected birds compared to the CC. Additionally, supplementation of crystalline arginine, glutamine, methionine, and threonine improved the apparent ileal digestibility of these specific amino acids on 6 dpi. Moreover, the THR treatment increased villus height in the duodenum. The ARG treatment decreased intestinal permeability and gene expression of amino acid transporters, whereas the GLN and THR treatments both reversed adverse effects of coccidiosis on gene expression of tight junction protein (claudin 1). However, the MET and COMB treatments exacerbated infection severity of coccidiosis. In summary, adding 0.75% of arginine, glutamine, or threonine in a low crude protein diet can improve the intestinal health of birds challenged with a mild coccidia infection.


Assuntos
Coccidiose , Eimeria , Doenças das Aves Domésticas , Ração Animal/análise , Animais , Arginina , Galinhas , Coccidiose/veterinária , Dieta/veterinária , Dieta com Restrição de Proteínas/veterinária , Suplementos Nutricionais , Glutamina , Absorção Intestinal , Masculino , Metionina , Nutrientes , Treonina
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