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2.
Biochim Biophys Acta Mol Basis Dis ; 1869(1): 166590, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36334837

RESUMO

Polymorphisms of phospholipase A2VIA (iPLA2ß or PLA2G6) are associated with body weights and blood C-reactive protein. The role of iPLA2ß/PLA2G6 in non-alcoholic steatohepatitis (NASH) is still elusive because female iPla2ß-null mice showed attenuated hepatic steatosis but exacerbated hepatic fibrosis after feeding with methionine- and choline-deficient diet (MCDD). Herein, female mice with myeloid- (MPla2g6-/-) and hepatocyte- (LPla2g6-/-) specific PLA2G6 deletion were generated and phenotyped after MCDD feeding. Without any effects on hepatic steatosis, MCDD-fed MPla2g6-/- mice showed further exaggeration of liver inflammation and fibrosis as well as elevation of plasma TNFα, CCL2, and circulating monocytes. Bone-marrow-derived macrophages (BMDMs) from MPla2g6-/- mice displayed upregulation of PPARγ and CEBPα proteins, and elevated release of IL6 and CXCL1 under LPS stimulation. LPS-stimulated BMDMs from MCDD-fed MPla2g6-/- mice showed suppressed expression of M1 Tnfa and Il6, but marked upregulation of M2 Arg1, Chil3, IL10, and IL13 as well as chemokine receptors Ccr2 and Ccr5. This in vitro shift was associated with exaggeration of hepatic M1/M2 cytokines, chemokines/chemokine receptors, and fibrosis genes. Contrarily, MCDD-fed LPla2g6-/- mice showed a complete protection which was associated with upregulation of Ppara/PPARα and attenuated expression of Pparg/PPARγ, fatty-acid uptake, triglyceride synthesis, and de novo lipogenesis genes. Interestingly, LPla2g6-/- mice fed with chow or MCDD displayed an attenuation of blood monocytes and elevation of anti-inflammatory lipoxin A4 in plasma and liver. Thus, PLA2G6 inactivation specifically in myeloid cells and hepatocytes led to opposing phenotypes in female mice undergoing NASH. Hepatocyte-specific PLA2G6 inhibitors may be further developed for treatment of this disease.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Feminino , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/genética , Fosfolipases A2 Independentes de Cálcio , PPAR gama/genética , Interleucina-6 , Lipopolissacarídeos , Dieta , Hepatócitos , Fenótipo , Metionina , Colina , Racemetionina , PPAR alfa , Receptores de Quimiocinas , Fosfolipases A2 do Grupo VI/genética
3.
J Nutr Biochem ; 111: 109176, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36220527

RESUMO

One-carbon metabolism is a key metabolic network that integrates nutritional signals with embryonic development. However, the response of one-carbon metabolism to methionine status and the regulatory mechanisms are poorly understood. Herein, we found that methionine supplementation during pregnancy significantly increased fetal number and average fetal weight. In addition, methionine modulated one-carbon metabolism primarily through 2 metabolic enzymes, cystathionine ß-synthase (CBS) and methionine adenosyltransferase 2A (MAT2A), which were significantly increased in fetal liver tissues and porcine trophoblast (pTr) cells in response to proper methionine supplementation. CBS and MAT2A overexpression enhanced the DNA synthesis in pTr cells. More importantly, we identified a transcription factor, DNA damage-inducible transcript 3 (DDIT3), that was the primary regulator of CBS and MAT2A, which bound directly to promoters and negatively regulated the expression of CBS and MAT2A. Taken together, our findings identified that DDIT3 targeting CBS and MAT2A was a novel regulatory pathway that mediated cellular one-carbon metabolism in response to methionine signal and provided promising targets to improve pregnancy health.


Assuntos
Metionina Adenosiltransferase , Metionina , Suínos , Animais , Metionina Adenosiltransferase/genética , Metionina Adenosiltransferase/metabolismo , Desenvolvimento Embrionário , Regiões Promotoras Genéticas , Racemetionina , Carbono
4.
Food Chem ; 404(Pt A): 134563, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36444035

RESUMO

The light-struck taste (LST) is a fault occurring in white and rosé wines associated to the formation of volatile sulfur compounds (VSCs) due to the reactions between riboflavin (RF) and methionine (Met). We investigated the possible preventing effect of 15 commercial tannins of different origin in model wine added with RF and Met, under oxic and anoxic conditions, and submitted to standardized light-exposure. All the tannins limited the degradation of Met in comparison to the tannin-free samples. Lower concentrations of VSCs were found in presence of tannins even under anoxia, condition favouring their formation. The sniffing trials evidenced the minor perception of cooked cabbage note with added tannins. The multivariate analysis showed the presence of flavan-3-ols was related to the formation of DMDS and DMTS, while tannic acid was related to MeSH, both the behaviors occurring under oxic condition. The study highlighted the ability of tannins to prevent the LST.


Assuntos
Taninos , Vinho , Humanos , Paladar , Racemetionina , Metionina , Hipóxia , Riboflavina , Compostos de Enxofre
5.
J Nutr Biochem ; 111: 109157, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36150682

RESUMO

Gata4 is a member of the zinc finger GATA transcription factor family and is required for liver development during the embryonic stage. Gata4 expression is repressed during NAFLD progression, however how it functions in this situation remains unclear. Here, Gata4 was deleted specifically in hepatocytes via Cre recombinase driven by the Alb promoter region. Under a high-fat diet (HFD) or methionine and choline deficient diet (MCD), Gata4 knockout (KO) male, but not female, mice displayed more severe NAFLD or NASH, evidenced by increased steatosis, fibrosis, as well as a higher NAS score and serum ALT level. The Gata4KO male liver exposed to a HFD or MCD had a reduced ratio of pACC/ACC, similar to the Gata4KO hepatocytes treated with palmitic acid. More cell apoptosis, which is associated with activated JNK signaling and inhibited NFκB signaling, was observed in the Gata4KO male liver and isolated hepatocytes. However, the inflammatory status in the Gata4KO male liver was similar to the control liver. Importantly, lower activation of AKT signaling in the liver, which is consistent with de-sensitized insulin signaling in isolated hepatocytes, was found in the Gata4KO male. In summary, our data demonstrated that loss of Gata4 in hepatocytes promoted NAFLD progression in male mice.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Masculino , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Insulina/metabolismo , Camundongos Endogâmicos C57BL , Hepatócitos/metabolismo , Fígado/metabolismo , Dieta Hiperlipídica/efeitos adversos , Apoptose , Metionina/metabolismo , Colina/farmacologia , Camundongos Knockout , Fator de Transcrição GATA4/genética , Fator de Transcrição GATA4/metabolismo
6.
Food Chem ; 401: 134178, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36099815

RESUMO

With raising consumer demand for plant-derived proteins, there has been an increased interest in the utilization of pea ingredients in food formulations. It was hypothesized that differences in processing history and composition affect their colloidal properties and their breakdown during in vitro simulated gastrointestinal digestion. The gastrointestinal fate of three different commercial pea protein ingredients, two protein isolates and one less refined concentrate was compared. The concentrate dispersion showed greater solubility, different protein composition and smaller particle size than the reconstituted pea protein isolates. When heat-treated, the release of free amino groups decreased for the isolates, but increased for the concentrate dispersions. LC-TQMS of free amino acids in the intestinal digestates indicated a significantly higher release of methionine (limiting amino acid in pea protein) in the concentrates than in the isolates. This work highlights the influence of processing and composition on techno-functional and digestion properties of pea ingredients.


Assuntos
Proteínas de Ervilha , Pós , Aminoácidos/metabolismo , Proteínas de Plantas/metabolismo , Metionina
7.
Food Chem ; 401: 134129, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36099821

RESUMO

In this study, quantitative monitoring of low-frequency (20 kHz) and high-frequency (355 kHz) ultrasound-induced inactivation of Kunitz (KTI) and Bowman-Birk inhibitor (BBI) using RP-HPLC was achieved, and its consistency with a traditional TI activity assay was verified. The effect of TI concentration, ultrasonic frequency, power density and pH on inactivation kinetics of KTI and BBI was explored. Results showed that the pseudo-first-order kinetic rate constants of KTI and BBI were decreased by over 60% when the initial TI concentration was increased from 100 mg/L to 1000 mg/L. Also, the amounts of inactivated KTI and BBI were increased by around 4-fold at the higher TI concentration of 1000 mg/L (20 kHz, 1.71 W/mL and pH 4). The colloidal environment and ultrasonic conditions influenced the secondary and tertiary structure and particle size of TIs in LF-induced inactivation. In comparison, the abovementioned conditions affected the oxidation of methionine and the conformational change of TIs in HF-induced inactivation.


Assuntos
Inibidor da Tripsina de Soja de Bowman-Birk , Inibidor da Tripsina de Soja de Bowman-Birk/química , Inibidor da Tripsina de Soja de Kunitz/química , Inibidores da Tripsina/química , Cinética , Ultrassom , Metionina
8.
Food Chem ; 401: 134072, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36108381

RESUMO

Plant growth regulator N-(2-chloro-4-pyridyl)-N'-phenylurea (CPPU) is widely used in fruit production. However, the mechanism in which CPPU affects melon fruit quality, especially aroma compound, remains unclear. Here, gas chromatography-mass spectrometry was performed to detect the sugar, citric acid, and aroma content in CPPU-treated and pollinated melon fruit. Results showed that the application of CPPU decreased the sugar and aroma content in melon fruit. The relative content of several important esters, including isobutyl acetate, ethyl acetate, 2-methylbutyl acetate, methyl acetate, benzyl acetate, and phenethyl acetate, in CPPU-treated fruits was significantly lower than that in honeybee-pollinated fruits. The content of many amino acids (isoleucine, leucine, valine, methionine, and l-phenylalanine), which could be metabolized into aroma compounds, in CPPU-treated fruits was significantly higher than that in honeybee-pollinated fruits. In conclusion, CPPU application interferes with amino-acid metabolism and affects the production of aromatic esters in melon fruit.


Assuntos
Cucurbitaceae , Compostos Orgânicos Voláteis , Abelhas , Animais , Frutas/metabolismo , Cucurbitaceae/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Açúcares/metabolismo , Isoleucina , Leucina/metabolismo , Metionina/metabolismo , Ácido Cítrico/metabolismo , Valina/metabolismo , Fenilalanina/metabolismo , Compostos Orgânicos Voláteis/metabolismo , Odorantes
9.
Cell Rep ; 41(6): 111598, 2022 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-36351405

RESUMO

Classically activated pro-inflammatory macrophages are generated from naive macrophages by pro-inflammatory cues that dynamically reprogram their fuel metabolism toward glycolysis. This increases their intracellular reactive oxygen species (ROS) levels, which then activate the transcription and release of pro-inflammatory mediators. Our study on mice that lack methionine sulfoxide reductase (Msr)-B1 shows that the resulting partial loss of protein methionine reduction in pro-inflammatory macrophages creates a unique metabolic signature characterized by altered fuel utilization, including glucose and pyruvate. This change also associates with hyper-inflammation that is at least partly due to sustained oxidation of an exposed methionine residue (M44) on glyceraldehyde 3-phosphate dehydrogenase (GAPDH), thereby inducing GAPDH aggregation, inflammasome activation, and subsequent increased interleukin (IL)-1ß secretion. Since MsrB1-knockout mice exhibit increased susceptibility to lipopolysaccharide (LPS)-induced sepsis, the MsrB1-GAPDH axis may be a key molecular mechanism by which protein redox homeostasis controls the metabolic profile of macrophages and thereby regulates their functions.


Assuntos
Ativação de Macrófagos , Metionina Sulfóxido Redutases , Camundongos , Animais , Metionina Sulfóxido Redutases/metabolismo , Oxirredução , Espécies Reativas de Oxigênio/metabolismo , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Metionina/metabolismo
10.
Nutrients ; 14(21)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36364766

RESUMO

LncRNA H19 has been reported to regulate apoptosis and neurological diseases. Hippocampal neuron apoptosis damages cognitive ability. Methionine restriction (MR) can improve cognitive impairment. However, the effect of MR on hippocampal neuronal apoptosis induced by a high-fat diet (HFD) in middle-aged mice remains unclear. For 25 weeks, middle-aged mice (C57BL/6J) were given a control diet (CON, 0.86% methionine + 4.2% fat), a high-fat diet (HFD, 0.86% methionine + 24% fat), or an HFD + MR diet (HFMR, 0.17% methionine + 24% fat). The HT22 cells were used to establish the early apoptosis model induced by high glucose (HG). In vitro, the results showed that MR significantly improved cell viability, suppressed the generation of ROS, and rescued HT22 cell apoptosis in a gradient-dependent manner. In Vivo, MR inhibited the damage and apoptosis of hippocampal neurons caused by a high-fat diet, reduced hippocampal oxidative stress, improved hippocampal glucose metabolism, relieved insulin resistance, and enhanced cognitive ability. Furthermore, MR could inhibit the overexpression of H19 and caspase-3 induced by HFD, HG, or H2O2 in vivo and in vitro, and promoted let-7a, b, e expression. These results indicate that MR can protect neurons from HFD-, HG-, or H2O2-induced injury and apoptosis by inhibiting H19.


Assuntos
Insulina , Metionina , Animais , Camundongos , Apoptose , Cognição , Dieta Hiperlipídica , Hipocampo/metabolismo , Peróxido de Hidrogênio/metabolismo , Insulina/metabolismo , Metionina/metabolismo , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Racemetionina/metabolismo
11.
Klin Lab Diagn ; 67(11): 625-632, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36398770

RESUMO

The role of the kidneys in the metabolism and homeostasis of sulfur-containing amino acids is great, so the levels of methionine (Met), total homocysteine (tHcy) and their ratios can be of diagnostic value in chronic kidney disease (CKD), in a course of the arterial hypertension (AH). The aim of the study was to evaluate the Met/tHcy ratio in hypertensive patients with CKD. We used blood plasma of 76 patients aged 40-75 years with AH and the excretory dysfunction of the kidneys; subgroups: 1 - with proteinuria (n=37); 2 - without proteinuria with glomerular filtration rate (GFR) < 90 ml/min/1.73 m2 (n=39) and comparison group 3 - patients with AH without renal excretory dysfunction (n=28). Significantly lower Met levels were in subgroup 1. THcy levels were higher in subgroups 1 and 2 than in group 3. The Met/tHcy ratio revealed differences in subgroups 1 and 2 vs group 3. No differences were found in Arg and Lys levels. Positive correlations of the Met/tHcy ratio with the number of erythrocytes, but not with the level of hemoglobin, were revealed. In the ROC analysis, the cut-off points for the Met/tHcy ratio compared to group 3 were 3.08 for subgroup 1 and 3.36 for subgroup 2. With the progression of CKD, there is an increase in the levels of tHcy in the blood, and a decrease in the content of Met. A decrease in GFR, especially in a case with proteinuria, is accompanied by a decrease in the level of Met. The Met/tHcy ratio above 3.36 can be considered as the minimum of the balance between these sulfur-containing amino acids contents in a blood necessary for hypertensive patients with CKD.


Assuntos
Hipertensão , Insuficiência Renal Crônica , Humanos , Metionina , Homocisteína , Racemetionina , Hipertensão/complicações , Proteinúria , Insuficiência Renal Crônica/complicações , Enxofre
12.
J Agric Food Chem ; 70(45): 14457-14467, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36342227

RESUMO

Methionine (Met) oxidation was observed during thermal degradation of methionine/glucose-derived Amadori rearrangement product (MG-ARP). The effects of oxidized methionine products, methionine sulfoxide (MetSO) and methionine sulfone (MetSO2), on pyrazine yields of the MG-ARP model were investigated. The pyrazine contents in the MG-ARP/Met and MG-ARP/MetSO models were found lower compared to those in the MG-ARP/MetSO2 model, and the inefficiency of pyrazine formation in the MG-ARP/Met model was proposed due to the fact that Met oxidation competitively inhibited the oxidation of dihydropyrazines for pyrazine formation in spite of relatively high methylglyoxal (MGO) content. The models of MGO mixed with Met, MetSO, or MetSO2 were established for further investigation of the mechanism for the involvement of Met oxidation in pyrazine formation. It was observed that the aldolization or carbonyl-amine reaction of MetSO with MGO was another important reason for the inhibition of pyrazine formation, except for the competitive inhibition of oxidative formation of MetSO on dihydropyrazine oxidation, and the adduct of MGO-MetSO was identified by MS/MS. These results also accounted for the phenomenon of low pyrazine yields but high yields of long-chain substituted pyrazines, which were converted from dihydropyrazines with the aldehyde involvement.


Assuntos
Glucose , Pirazinas , Espectrometria de Massas em Tandem , Óxido de Magnésio , Metionina/metabolismo , Oxirredução , Racemetionina/metabolismo
13.
Orphanet J Rare Dis ; 17(1): 417, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36376887

RESUMO

BACKGROUND: Betaine is an "alternate" methyl donor for homocysteine remethylation catalyzed by betaine homocysteine methyltransferase (BHMT), an enzyme mainly expressed in the liver and kidney. Betaine has been used for more than 30 years in pyridoxine non-responsive cystathionine beta-synthase (pnrCBS) and cobalamin C (cblC) deficiencies to lower the hyperhomocysteinemia, although little is known about the optimal therapeutic dosage and its pharmacokinetic in these patients. AIMS: We compared 2 betaine doses (100 mg/kg/day vs. 250 mg/kg/day) in children affected by pnrCBS or cblC deficiencies. We also measured the pharmacokinetics parameters after a single dose of betaine (100 or 250 mg/kg) in these patients. METHODS: We conducted a prospective, randomized, crossover clinical trial with blinded evaluation. The primary outcome was the equivalence of total plasma homocysteine (tHcy) concentrations upon one-month oral treatment with betaine at 100 versus 250 mg/kg/day. RESULTS: Eleven patients completed the study (5 pnrCBS and 6 cblC). tHcy concentrations were equivalent after a one-month treatment period for the two betaine dosages. Multivariate analysis showed a significant effect of betaine dose on methionine (Met) (p = 0.01) and S-adenosylmethionine (SAM) concentrations (p = 0.006). CONCLUSIONS: Our analysis shows that there is no overt benefit to increasing betaine dosage higher than 100 mg/kg/day to lower tHcy concentrations in pnrCBS and cblC deficiencies. However, increasing betaine up to 250 mg/kg/d could benefit cblC patients through the increase of methionine and SAM concentrations, as low Met and SAM concentrations are involved in the pathophysiology of this disease. In contrast, in pnrCBS deficiency, betaine doses higher than 100 mg/kg/day could be harmful to these patients with pre-existing hypermethioninemia. TRIAL REGISTRATION: Clinical Trials, NCT02404337. Registered 23 May 2015-prospectively registered, https://clinicaltrials.gov .


Assuntos
Homocistinúria , Deficiência de Vitamina B 12 , Humanos , Criança , Betaína/uso terapêutico , Estudos Prospectivos , Homocistinúria/tratamento farmacológico , Cistationina beta-Sintase/uso terapêutico , Metionina , S-Adenosilmetionina/uso terapêutico , Homocisteína
14.
Nutr Res ; 107: 218-227, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36351308

RESUMO

Many studies have suggested that folate plays a role in preeclampsia (PE) risks, but few studies have assessed folate-related 1-carbon metabolism (OCM)-related nutrients with the risk of PE. We hypothesized that OCM-related nutrients are associated with PE. A 1:1 matched case-control study was conducted to explore the association between dietary OCM-related nutrients intake and the risk of PE in pregnant Chinese women. Four hundred and forty pairs of pregnant women with PE and hospital-based, healthy pregnant women, matched according to gestational week (±1 week) and age (±3 years), were recruited. Dietary intake was assessed using a validated 78-item semiquantitative food frequency questionnaire. Multivariate conditional logistic regression was used to estimate odds ratios (ORs) and 95% CIs. Restricted cubic splines were plotted to evaluate the dose-response relationship between dietary OCM-related nutrient intake and the risk of PE. Intake of folate, vitamin B6, vitamin B12, methionine, and total choline were inversely related to the risk of PE after adjustment for covariates (all P trend < .05). Adjusted ORs (95% CIs) for quartile 4 versus quartile 1 were 0.71 (0.55-0.93) for folate, 0.66 (0.50-0.87) for vitamin B6, 0.68 (0.52-0.88) for vitamin B12, 0.77 (0.60-0.81) for methionine, and 0.67 (0.51-0.87) for total choline. This study suggests that dietary OCM-related nutrients intake is associated with lower odds of PE in pregnant Chinese women.


Assuntos
Pré-Eclâmpsia , Gestantes , Feminino , Humanos , Gravidez , Estudos de Casos e Controles , Pré-Eclâmpsia/prevenção & controle , Ingestão de Alimentos , Nutrientes , Vitamina B 12 , Vitamina B 6 , Ácido Fólico , Racemetionina , Metionina , Piridoxina , Colina , Vitaminas
15.
Nutrients ; 14(21)2022 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-36364822

RESUMO

The association between methionine intake and cognitive function is inconclusive. We aimed to assess the association between methionine intake and cognitive function in Chinese adults and to explore the interaction between methionine and lead intake. Data from 4852 adults aged ≥55 years from the China Health and Nutrition Survey were used. Cognitive function was measured in 1997, 2000, 2004, and 2006. A 3-day, 24-hour recall was used to assess methionine and lead intake from different protein sources. Multivariable mixed linear regression was used in the analyses. Total methionine intake was positively correlated with cognition. There was a significant interaction between animal methionine and lead intakes. In subgroup analyses, across the quartiles of animal methionine intake, the regression coefficients (95% CI) for global cognition were 0.00, 0.57 (0.17 to 0.98), 1.18 (0.73 to 1.62), and 1.80 (1.31 to 2.29), respectively, while they were 0.00, -0.73 (-1.12 to -0.34), -0.83 (-1.26 to -0.41), and -1.72 (-2.22 to -1.22) across the quartiles of plant methionine intake, respectivelyThe association between animal methionine intake and cognition was stronger among adults with a low lead intake. In conclusion, animal methionine and plant methionine intake were positively and inversely associated with cognition, respectively. Lead intake modified the association between animal methionine intake and cognition.


Assuntos
Dieta , Metionina , Animais , Cognição , Inquéritos Nutricionais , China
16.
Cells ; 11(22)2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36429035

RESUMO

Stem cells are a population of undifferentiated cells with self-renewal and differentiation capacities. Normal and cancer stem cells share similar characteristics in relation to their stemness properties. One-carbon metabolism (OCM), a network of interconnected reactions, plays an important role in this dependence through its role in the endogenous synthesis of methionine and S-adenosylmethionine (SAM), the universal donor of methyl groups in eukaryotic cells. OCM genes are differentially expressed in stem cells, compared to their differentiated counterparts. Furthermore, cultivating stem cells in methionine-restricted conditions hinders their stemness capacities through decreased SAM levels with a subsequent decrease in histone methylation, notably H3K4me3, with a decrease in stem cell markers. Stem cells' reliance on methionine is linked to several mechanisms, including high methionine flux or low endogenous methionine biosynthesis. In this review, we provide an overview of the recent discoveries concerning this metabolic dependence and we discuss the mechanisms behind them. We highlight the influence of SIRT1 on SAM synthesis and suggest a role of PGC-1α/PPAR-α in impaired stemness produced by methionine deprivation. In addition, we discuss the potential interest of methionine restriction in regenerative medicine and cancer treatment.


Assuntos
Metionina , Neoplasias , Metionina/metabolismo , Sirtuína 1 , PPAR alfa , Racemetionina , S-Adenosilmetionina/metabolismo , Células-Tronco Neoplásicas/metabolismo
17.
Int J Mol Sci ; 23(22)2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36430532

RESUMO

This review examines the impact of reactive species RS (of oxygen ROS, nitrogen RNS and halogens RHS) on various amino acids, analyzed from a reactive point of view of how during these reactions, the molecules are hydroxylated, nitrated, or halogenated such that they can lose their capacity to form part of the proteins or peptides, and can lose their function. The reactions of the RS with several amino acids are described, and an attempt was made to review and explain the chemical mechanisms of the formation of the hydroxylated, nitrated, and halogenated derivatives. One aim of this work is to provide a theoretical analysis of the amino acids and derivatives compounds in the possible positions. Tyrosine, methionine, cysteine, and tryptophan can react with the harmful peroxynitrite or •OH and •NO2 radicals and glycine, serine, alanine, valine, arginine, lysine, tyrosine, histidine, cysteine, methionine, cystine, tryptophan, glutamine and asparagine can react with hypochlorous acid HOCl. These theoretical results may help to explain the loss of function of proteins subjected to these three types of reactive stresses. We hope that this work can help to assess the potential damage that reactive species can cause to free amino acids or the corresponding residues when they are part of peptides and proteins.


Assuntos
Aminoácidos , Cisteína , Aminoácidos/metabolismo , Triptofano , Proteínas , Metionina , Tirosina
18.
Int J Mol Sci ; 23(22)2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36430781

RESUMO

Transient receptor potential (TRP) ankyrin repeat 1 (TRPA1), which is involved in inflammatory pain sensation, is activated by endogenous factors, such as intracellular Zn2+ and hydrogen peroxide, and by irritant chemical compounds. The synthetic compound JT010 potently and selectively activates human TRPA1 (hTRPA1) among the TRPs. Therefore, JT010 is a useful tool for analyzing TRPA1 functions in biological systems. Here, we show that JT010 is a potent activator of hTRPA1, but not mouse TRPA1 (mTRPA1) in human embryonic kidney (HEK) cells expressing hTRPA1 and mTRPA1. Application of 0.3-100 nM of JT010 to HEK cells with hTRPA1 induced large Ca2+ responses. However, in HEK cells with mTRPA1, the response was small. In contrast, both TRPA1s were effectively activated by allyl isothiocyanate (AITC) at 10-100 µM. Similar selective activation of hTRPA1 by JT010 was observed in electrophysiological experiments. Additionally, JT010 activated TRPA1 in human fibroblast-like synoviocytes with inflammation, but not TRPA1 in mouse dorsal root ganglion cells. As cysteine at 621 (C621) of hTRPA1, a critical cysteine for interaction with JT010, is conserved in mTRPA1, we applied JT010 to HEK cells with mutations in mTRPA1, where the different residue of mTRPA1 with tyrosine at 60 (Y60), with histidine at 1023 (H1023), and with asparagine at 1027 (N1027) were substituted with cysteine in hTRPA1. However, these mutants showed low sensitivity to JT010. In contrast, the mutation of hTRPA1 at position 669 from phenylalanine to methionine (F669M), comprising methionine at 670 in mTRPA1 (M670), significantly reduced the response to JT010. Moreover, the double mutant at S669 and M670 of mTRPA1 to S669E and M670F, respectively, induced slight but substantial sensitivity to 30 and 100 nM JT010. Taken together, our findings demonstrate that JT010 potently and selectively activates hTRPA1 but not mTRPA1.


Assuntos
Canais de Potencial de Receptor Transitório , Humanos , Canais de Potencial de Receptor Transitório/genética , Canais de Cálcio/genética , Canal de Cátion TRPA1/genética , Cisteína , Cálcio/metabolismo , Metionina
19.
Nutrients ; 14(22)2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36432434

RESUMO

BACKGROUND: Previous experimental studies showed that limiting methionine in the diet of animals or in cell culture media suppresses mammary cancer cell proliferation or metastasis. However, no previous study has investigated the associations of changes in methionine intake with survival among breast cancer survivors. We aimed to examine the association between changes in dietary intake of methionine, folate/folic acid, and vitamin B12 from before to after diagnosis of breast cancer, and mortality among breast cancer survivors. METHODS: We included 1553 postmenopausal women from the Women's Health Initiative who were diagnosed with invasive breast cancer and completed a food frequency questionnaire both before and after breast cancer diagnosis. Multivariable Cox proportional hazards regression models were used to estimate adjusted hazard ratios (HRs) and 95% confidence (CIs) of all-cause and breast cancer mortality associated with changes in methionine intake and changes in folate/folic acid and vitamin B12 intake. RESULTS: Relative to pre-diagnosis, 28% of women decreased methionine intake by ≥20%, 30% of women increased methionine intake by ≥20%, and 42% of women had a relatively stable methionine intake (±19.9%) following breast cancer diagnosis. During a mean 16.1 years of follow up, there were 772 deaths in total, including 195 deaths from breast cancer. Compared to women with relatively stable methionine intake, women with decreased methionine intake had lower risks of all-cause (HR 0.78, 95% CI 0.62-0.97) and breast cancer mortality (HR 0.58, 95% CI 0.37-0.91) in fully adjusted models. In contrast, increased methionine intake or changes in folate/folic acid or vitamin B12 intake were not associated with all-cause or breast cancer mortality. CONCLUSIONS: Among breast cancer survivors, decreased methionine intake after breast cancer diagnosis was associated with lower risk of all-cause and breast cancer mortality.


Assuntos
Neoplasias , Vitamina B 12 , Feminino , Animais , Ácido Fólico/metabolismo , Metionina/metabolismo , Pós-Menopausa , Estudos Prospectivos , Fatores de Risco , Racemetionina , Ingestão de Alimentos
20.
Clin Imaging ; 92: 124-130, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36374712

RESUMO

PURPOSE: Amino acid positron emission tomography (PET) may provide additional information to computed tomography and magnetic resonance imaging for detecting the pretreatment diagnosis of intracranial lesions. The purpose of this study was to investigate the role of cutoff values of 11C-METPET, an amino acid PET tracer, in the differentiation of pretreatment brain tumors from non-neoplastic lesions. METHODS: This retrospective cohort study analyzed 101 pretreatment patients with a definitive diagnosis out of a total of 425 consecutive 11C-METPET imaging studies. The standardized uptake values (SUV) and the ratios of lesion to contralateral normal frontal-lobe gray matter uptake (L/N ratios) were measured. Cutoff values for the differential diagnosis of brain tumors from non-neoplastic lesions were determined using receiver operating characteristics curve (ROC) analysis. RESULTS: Based on the ROC analyses, the cutoffs were 3.33 for maximum SUV, 2.54 for mean SUV, 2.33 for peak SUV, 2.04 for Lmax/Nmean, and 2.23 for Lmax/Nmax. The sensitivity and specificity of these cutoffs were 69.2% and 82.6%, respectively, for maximum SUV, 64.1% and 91.3% for mean SUV, 69.2% and 91.3% for peak SUV, 70.5% and 91.3% for Lmax/Nmax and 75.6% and 82.6% for Lmax/Nmean. CONCLUSION: In differentiating intracranial brain tumor from non-neoplastic lesion with 11C-METPET, the use of optimal cutoff values indicates the high specificity, which means that positive result indicates the high likelihood of brain tumor. Considering the high specificity of 11C-METPET, more invasive examinations such as biopsy may be considered in positive cases.


Assuntos
Neoplasias Encefálicas , Tomografia por Emissão de Pósitrons , Humanos , Radioisótopos de Carbono/metabolismo , Estudos Retrospectivos , Tomografia por Emissão de Pósitrons/métodos , Neoplasias Encefálicas/patologia , Metionina/metabolismo , Diagnóstico Diferencial , Compostos Radiofarmacêuticos
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