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1.
Am J Clin Nutr ; 111(3): 644-656, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31915809

RESUMO

BACKGROUND: Choline-related nutrients are dietary precursors of a gut microbial metabolite, trimethylamine-N-oxide, which has been linked to cardiometabolic diseases and related death. However, epidemiologic evidence on dietary choline and mortality remains limited, particularly among nonwhite populations. OBJECTIVES: This study aimed to investigate the associations of choline-related nutrients with cardiometabolic and all-cause mortality among black and white Americans and Chinese adults. METHODS: Included were 49,858 blacks, 23,766 whites, and 134,001 Chinese, aged 40-79 y, who participated in 3 prospective cohorts and lived ≥1 y after enrollment. Cox regression models were used to estimate HRs and 95% CIs for cardiometabolic [e.g., ischemic heart disease (IHD), stroke, and diabetes] and all-cause deaths. To account for multiple testing, P values < 0.003 were considered significant. RESULTS: Mean choline intake among blacks, whites, and Chinese was 404.1 mg/d, 362.0 mg/d, and 296.8 mg/d, respectively. During a median follow-up of 11.7 y, 28,673 deaths were identified, including 11,141 cardiometabolic deaths. After comprehensive adjustments, including for overall diet quality and disease history, total choline intake was associated with increased cardiometabolic mortality among blacks and Chinese (HR for highest compared with lowest quintile: 1.26; 95% CI: 1.13, 1.40 and HR: 1.23; 95% CI: 1.11, 1.38, respectively; both P-trend < 0.001); among whites, the association was weaker (HR: 1.12; 95% CI: 0.95, 1.33; P-trend = 0.02). Total choline intake was also associated with diabetes and all-cause mortality in blacks (HR: 1.66; 95% CI: 1.26, 2.19 and HR: 1.20; 95% CI: 1.12, 1.29, respectively), with diabetes mortality in Chinese (HR: 2.24; 95% CI: 1.68, 2.97), and with IHD mortality in whites (HR: 1.31; 95% CI: 1.02, 1.69) (all P-trend < 0.001). The choline-mortality association was modified by alcohol consumption and appeared stronger among individuals with existing cardiometabolic disease. Betaine intake was associated with increased cardiometabolic mortality in Chinese only (HR: 1.16; 95% CI: 1.08, 1.25; P-trend < 0.001). CONCLUSIONS: High choline intake was associated with increased cardiometabolic mortality in racially diverse populations.


Assuntos
Doenças Cardiovasculares/etnologia , Doenças Cardiovasculares/mortalidade , Colina/metabolismo , Adulto , Grupo com Ancestrais do Continente Africano , Idoso , Grupo com Ancestrais do Continente Asiático , Doenças Cardiovasculares/metabolismo , Grupo com Ancestrais do Continente Europeu , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
2.
Nat Commun ; 11(1): 388, 2020 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-31959751

RESUMO

Bacterial microcompartments (BMCs) are prokaryotic organelles consisting of a protein shell and an encapsulated enzymatic core. BMCs are involved in several biochemical processes, such as choline, glycerol and ethanolamine degradation and carbon fixation. Since non-native enzymes can also be encapsulated in BMCs, an improved understanding of BMC shell assembly and encapsulation processes could be useful for synthetic biology applications. Here we report the isolation and recombinant expression of BMC structural genes from the Klebsiella pneumoniae GRM2 locus, the investigation of mechanisms behind encapsulation of the core enzymes, and the characterization of shell particles by cryo-EM. We conclude that the enzymatic core is encapsulated in a hierarchical manner and that the CutC choline lyase may play a secondary role as an adaptor protein. We also present a cryo-EM structure of a pT = 4 quasi-symmetric icosahedral shell particle at 3.3 Å resolution, and demonstrate variability among the minor shell forms.


Assuntos
Proteínas de Bactérias/metabolismo , Klebsiella pneumoniae/citologia , Liases/metabolismo , Organelas/ultraestrutura , Proteínas de Bactérias/genética , Colina/metabolismo , Microscopia Crioeletrônica , Loci Gênicos , Klebsiella pneumoniae/enzimologia , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/ultraestrutura , Liases/genética , Organelas/enzimologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Biologia Sintética
3.
J Dairy Sci ; 103(1): 282-300, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31677842

RESUMO

The objectives were to use meta-analytic methods to determine the effects of amount of supplemental choline ion as rumen-protected choline (RPC) starting prepartum on production and health of dairy cows. The literature was systematically reviewed and 21 experiments, with up to 66 treatment means and 1,313 prepartum parous cows, were included. All experiments had a treatment with no supplemental choline (0 g/d; n = 30 treatment means), and the amount of choline ion supplemented to treated cows ranged from 5.6 to 25.2 g/d (n = 36 treatment means). Duration of pre- and postpartum feeding of RPC averaged (±standard deviation) 22.0 ± 6.0 and 57.5 ± 42.2 d, respectively. Data collected included the ingredient composition and chemical analyses of pre- and postpartum diets, amount of choline ion supplemented, number of cows per treatment, frequency of health events, and the least squares means and respective standard error of the means for production responses, liver composition, and blood parameters. The concentrations of net energy for lactation and metabolizable amino acids and protein (MP) in pre- and postpartum diets were predicted for each treatment mean using National Research Council (2001). Mixed model meta-analysis was conducted including the random effect of experiment and weighting by the inverse of the standard error of the means squared. Increasing supplementation of choline ion during transition linearly increased pre- (ß = 0.0184 ± 0.00425) and postpartum dry matter intake (ß = 0.0378 ± 0.00974), and yields of milk (ß = 0.436 ± 0.112), energy-corrected milk (ECM; ß = 0.422 ± 0.0992), fat (ß = 0.00555 ± 0.000793), and protein (ß = 0.0138 ± 0.00378). Nevertheless, an interaction between choline and postpartum metabolizable methionine as a percent of MP (METMPPo) was observed for yields of milk, ECM, and protein because as METMPPo increased, the positive response to choline on yields of milk, ECM, and protein decreased. Supplementing choline during transition tended to reduce the risks of retained placenta and mastitis, but it had no effect on metritis, milk fever, displaced abomasum and ketosis, or the concentration of triacylglycerol in the hepatic tissue postpartum. The median amount of choline ion supplemented was 12.9 g/d and responses in postpartum dry matter intake and yields of milk, ECM, fat, and protein to that amount of supplementation were 0.5, 1.6, 1.7, 0.07, and 0.05 kg/d, respectively. No interactions were observed between supplemental choline and prepartum dietary net energy for lactation or metabolizable methionine as a percent of MP. Collectively, feeding RPC during the transition period improves performance in parous cows. Increases in yields of milk and milk components were observed in spite of pre- and postpartum diets, although the increments in milk, ECM, and protein yields with supplementing choline decreased as the concentration of methionine in postpartum diets increased. The optimum dose of choline ion was not detected, but likely it is more than the 12.9 g/d fed in most experiments evaluated in the current meta-analysis. Finally, the meta-analysis identified lack of sufficient data to understand the role of supplemental choline in nulliparous cows.


Assuntos
Bovinos/fisiologia , Colina/metabolismo , Rúmen/metabolismo , Ração Animal/análise , Animais , Colina/administração & dosagem , Dieta/veterinária , Suplementos Nutricionais/análise , Feminino , Lactação/fisiologia
4.
J Agric Food Chem ; 67(48): 13247-13257, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31707781

RESUMO

Dietary interventions alter the formation of the disease-associated metabolite, trimethylamine (TMA), via intestinal microbial TMA lyase activity. Nevertheless, the mechanisms regulating microbial enzyme production are still unclear. Sequencing of the gut bacteria 16S rDNA demonstrated that dietary intervention changed the composition of the gut microbiota and the functional metagenome involved in the choline utilization pathway. Characterization of the functional profile of the metagenomes and metabonomics analysis revealed that a series of Kyoto Encyclopedia of Genes and Genomes orthologous groups and enzyme groups related to accumulation of methylglyoxal (MG) and glycine were enriched in red meat diet-fed animals, whereas fiber-rich diet suppressed glycine formation via the MG-dependent pathway. Our observations suggest associations between choline-TMA lyase expression and MG formation, which are indicative of a novel role of the gut microbiota in choline metabolism and highlight it as a potential target for inhibiting TMA production.


Assuntos
Bactérias/metabolismo , Colina/metabolismo , Fibras na Dieta/metabolismo , Microbioma Gastrointestinal , Metilaminas/metabolismo , Aldeído Pirúvico/metabolismo , Ração Animal/análise , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Glicina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Carne Vermelha/análise
5.
J Dairy Sci ; 102(11): 10291-10303, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31477291

RESUMO

Maternal supply of methyl donors such as methionine (Met) during late pregnancy can affect offspring growth and development. The objective was to investigate the effect of postruminal Met supply during late pregnancy on 1-carbon, Met cycle, and transsulfuration pathways in the calf liver. During the last 28 d of pregnancy, cows were individually fed a control diet or the control diet plus rumen-protected dl-Met (MET; 0.09% dry matter intake). Liver samples obtained from calves (n = 14/group) at 4, 14, 28, and 50 d of age were used for metabolomics, real-time PCR, and enzyme activity analyses. Genes associated with 1-carbon metabolism, DNA methylation, and the cytidine 5'-diphosphocholine-choline pathway were analyzed via real-time PCR. Activity of betaine homocysteine methyltransferase, cystathionine ß-synthase, and 5-methyltetrahydrofolate homocysteine methyltransferase (MTR) was analyzed using 14C isotopes. Data were analyzed using a mixed model that included the fixed effects of maternal treatment, day, and their interaction, and the random effect was calf within maternal diet. Calves born to dams offered MET tended to have greater birth body weight and had overall greater body weight during the first 9 wk of life. However, no differences were detected for daily feed intake and average daily gain between groups. Concentrations of betaine and choline, reflecting Met cycle activity, at d 14 through 28 were greater in MET calves. Transsulfuration pathway intermediates also were altered in MET calves, with concentrations of cysteine sulfinic acid and hypotaurine (d 4 and 14) and taurine being greater (d 4, 14, 28, and 50). Despite the lack of differences in daily feed intake, the greater concentrations of the tricarboxylic acid cycle intermediates fumarate and glutamate along with NAD/NADH in MET calves indicated enhanced rates of energy metabolism. Although activity of betaine homocysteine methyltransferase was greater in MET calves at d 14, cystathionine ß-synthase was lower and increased at d 14 and 28, where it was greater compared with the control diet. Activity of MTR was lower at d 4 and 50 in MET calves. Among gene targets measured, MET calves had greater overall expression of MTR, phosphatidylethanolamine N-methyltransferase, and choline kinase α and ß. An interaction of maternal diet by time was detected for mRNA abundance of DNA methyltransferase 3α (involved in de novo methylation) due to greater values at d 4 and 14 in MET calves. Overall, the data indicate that enhanced postruminal supply of Met to cows during late pregnancy may program hepatic metabolism of the calf in the context of maintaining Met homeostasis, phosphatidylcholine and taurine synthesis, DNA methylation, and energy metabolism. These alterations potentially result in better efficiency of nutrient use, hence conferring the calf a physiologic advantage during a period of rapid growth and development. The precise biologic mechanisms remain to be established.


Assuntos
Betaína-Homocisteína S-Metiltransferase/metabolismo , Carbono/metabolismo , Bovinos/fisiologia , Metabolismo Energético , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Metionina/administração & dosagem , Animais , Animais Recém-Nascidos , Betaína/metabolismo , Betaína-Homocisteína S-Metiltransferase/genética , Biomarcadores/metabolismo , Bovinos/genética , Bovinos/crescimento & desenvolvimento , Colina/metabolismo , Dieta/veterinária , Epigênese Genética , Feminino , Fígado/enzimologia , Parto , Gravidez , Fenômenos Fisiológicos da Nutrição Pré-Natal , RNA Mensageiro/metabolismo , Rúmen/metabolismo
6.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1864(12): 158516, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31473345

RESUMO

In the metabolism of pulmonary surfactant, the ATP-binding cassette sub-family A member 3 (ABCA3) is a crucial protein in the formation of the storage compartment for surfactant, the lamellar body (LB), and the transport of phospholipids in it. Mutations in ABCA3 not only disturb surfactant metabolism but also cause chronic interstitial lung diseases. Assays for ABCA3 transport function are needed to investigate pathophysiology of the mutations and treatment options for the patients. We metabolically labeled choline (Cho) head phospholipids with the Cho analogue, propargyl-Cho. The universal incorporation of propargyl-Cho was confirmed by mass spectrometry and labeled lipids were visualized in confocal microscopy by click reaction with an azide fluorophore. After pulse-labeling propargyl-Cho labeled lipids accumulated in ABCA3+ vesicles in a time and concentration dependent manner. When treated with the choline kinase inhibitor MN58b during the first 12 h, the lipids intensity inside ABCA3+ vesicles decreased, whereas intensity was unchanged when treated after 12 h. Miltefosine, a substrate of ABCA3, decreased the incorporation of labeled lipids in ABCA3+ vesicles at all time points. The lipids intensity inside the mutated (p.N568D or p.L1580P) ABCA3+ vesicles was decreased compared to wild type, while the intensity outside of vesicles showed no difference. Propargyl-Cho can metabolically pulse-label Cho phospholipids. Visualization and quantification of fluorescence intensity of the labeled lipids inside ABCA3+ vesicles at equilibrium can specifically assess the transport function of ABCA3.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Colina/metabolismo , Fosfolipídeos/metabolismo , Transporte Biológico Ativo , Colina/análise , Química Click , Células HEK293 , Humanos , Microscopia Confocal , Fosfolipídeos/química
7.
Med Hypotheses ; 130: 109271, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31383335

RESUMO

Recent clinical studies show a positive correlation between elevated plasma TMAO and increased cardiovascular risk. However, the mechanism of the increase and biological effects of TMAO in the circulatory system are obscure. Plasma TMAO level depends mostly on the following three factors. First, the liver produces TMAO from TMA, a gut bacteria metabolite of dietary choline and carnitine. Second, plasma TMAO increases after ingestion of dietary TMAO from fish and seafood. Finally, plasma TMAO depends on TMAO and TMA excretion by the kidneys. Ample evidence highlights protective functions of TMAO, including the stabilization of proteins and cells exposed to hydrostatic and osmotic stresses, for example in fish exposed to hydrostatic stress (deep water) and osmotic stress (salty water). Osmotic stress and hydrostatic stresses are augmented in cardiovascular diseases such as hypertension. In hypertensive subjects a diastole-systole change in hydrostatic pressure in the heart may exceed 220 mmHg with a frequency of 60-220/min. This produces environment in which hydrostatic pressure changes over 100,000 times per 24 h. Furthermore, cardiovascular diseases are associated with disturbances in water-electrolyte balance which produce changes in plasma osmolarity. Perhaps, the increase in plasma TMAO in cardiovascular diseases is analogous to increased level of plasma natriuretic peptide B, which is both a cardiovascular risk marker and a compensatory response producing beneficial effects for pressure/volume overloaded heart. In this regard, there is some evidence that a moderate increase in plasma TMAO due to TMAO supplementation may be beneficial in animal model of hypertension-related heart failure. Finally, increased plasma TMAO is present in humans consuming seafood-rich diet which is thought to be health-beneficial. We hypothesize that increased plasma TMAO serves as a compensatory response mechanism which protects cells from hydrostatic and osmotic stresses.


Assuntos
Doenças Cardiovasculares/sangue , Metilaminas/sangue , Pressão Osmótica , Animais , Sistema Cardiovascular , Carnitina/metabolismo , Colina/metabolismo , Dieta , Humanos , Pressão Hidrostática , Rim/metabolismo , Fígado/metabolismo , Camundongos , Modelos Teóricos , Ratos , Fatores de Risco
8.
J Dairy Sci ; 102(11): 10395-10410, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31447151

RESUMO

Neutrophils are the most important polymorphonuclear leukocytes (PMNL), representing the front-line defense involved in pathogen clearance upon invasion. As such, they play a pivotal role in immune and inflammatory responses. Isolated PMNL from 5 mid-lactating Holstein dairy cows were used to evaluate the in vitro effect of methionine (Met) and choline (Chol) supplementation on mRNA expression of genes related to the Met cycle and innate immunity. The target genes are associated with the Met cycle, cell signaling, inflammation, antimicrobial and killing mechanisms, and pathogen recognition. Treatments were allocated in a 3 × 3 factorial arrangement, including 3 Lys-to-Met ratios (L:M, 3.6:1, 2.9:1, or 2.4:1) and 3 levels of supplemental Chol (0, 400, or 800 µg/mL). Three replicates per treatment group were incubated for 2 h at 37°C and 5% atmospheric CO2. Both betaine-homocysteine S-methyltransferase and choline dehydrogenase were undetectable, indicating that PMNL (at least in vitro) cannot generate Met from Chol through the betaine pathway. The PMNL incubated without Chol experienced a specific state of inflammatory mediation [greater interleukin-1ß (IL1B), myeloperoxidase (MPO), IL10, and IL6] and oxidative stress [greater cysteine sulfinic acid decarboxylase (CSAD), cystathionine gamma-lyase (CTH), glutathione reductase (GSR), and glutathione synthase (GSS)]. However, data from the interaction L:M × Chol indicated that this negative state could be overcome by supplementing additional Met. This was reflected in the upregulation of methionine synthase (MTR) and toll-like receptor 2 (TLR2); that is, pathogen detection ability. At the lowest level of supplemental Chol, Met downregulated GSS, GSR, IL1B, and IL6, suggesting it could reduce cellular inflammation and enhance antioxidant status. At 400 µg/mL Chol, supplemental Met upregulated PMNL recognition capacity [higher TLR4 and L-selectin (SELL)]. Overall, enhancing the supply of methyl donors to isolated unstimulated PMNL from mid-lactating dairy cows leads to a low level of PMNL activation and upregulates a cytoprotective mechanism against oxidative stress. Enhancing the supply of Met coupled with adequate Chol levels enhances the gene expression of PMNL pathogen-recognition mechanism. These data suggest that Chol supply to PMNL exposed to low levels of Met effectively downregulated the entire repertoire of innate inflammatory-responsive genes. Thus, Met availability in PMNL during an inflammatory challenge may be sufficient for mounting an appropriate biologic response.


Assuntos
Bovinos/sangue , Colina/administração & dosagem , Metionina/administração & dosagem , Neutrófilos/metabolismo , 5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase , Animais , Antioxidantes/metabolismo , Bovinos/imunologia , Bovinos/fisiologia , Colina/genética , Colina/metabolismo , Dieta/veterinária , Regulação para Baixo , Feminino , Expressão Gênica , Imunidade Inata/genética , Inflamação/genética , Inflamação/veterinária , Lactação/efeitos dos fármacos , Metionina/genética , Metionina/metabolismo , Neutrófilos/imunologia , Estresse Oxidativo/genética , RNA Mensageiro/metabolismo
9.
Anticancer Res ; 39(8): 4061-4064, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366488

RESUMO

BACKGROUND/AIM: Circulating tumor cells (CTCs) may have an important role in metastasis. CTC clusters, which contain fibroblasts, indicate poor prognosis. In the present study, we used our malignant lymphoma metastatic mouse model to compare the effect of a choline-deficient-diet (CDD) and the control diet (CD) on fibroblasts in CTCs. MATERIALS AND METHODS: We compared the number and morphology of CTCs in CDD and CD mice using color-coded imaging with fluorescent proteins. Malignant lymphoma EL4 cells expressing RFP were injected in the spleen of transgenic C57B/6-GFP mice, which were fed a CDD or CD. Two weeks later, we harvested and observed the number of CTCs and fibroblast-like cells both in heart blood and portal blood. Imaging of CTC morphology was performed with smeared glass slides and in culture. RESULTS AND CONCLUSION: There was no significant difference in the number of CTCs between CDD and CD mice. The number of fibroblast-like cells in the CTC microenvironment in CD mouse portal blood was significantly larger than in CDD mouse portal blood. These differences may be caused by deficiency in choline that leads to less metastasis in choline-deficient-diet-induced fatty liver.


Assuntos
Colina/metabolismo , Linfoma/sangue , Células Neoplásicas Circulantes/metabolismo , Células Estromais/metabolismo , Animais , Linhagem Celular Tumoral , Deficiência de Colina/sangue , Deficiência de Colina/genética , Deficiência de Colina/patologia , Dieta/efeitos adversos , Modelos Animais de Doenças , Fibroblastos/metabolismo , Fibroblastos/patologia , Proteínas de Fluorescência Verde/química , Humanos , Proteínas Luminescentes/química , Linfoma/genética , Linfoma/patologia , Camundongos , Camundongos Transgênicos , Metástase Neoplásica , Células Neoplásicas Circulantes/patologia , Células Estromais/patologia , Microambiente Tumoral/genética
10.
Environ Sci Pollut Res Int ; 26(29): 29763-29779, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31407264

RESUMO

Dibutyl phthalate (DBP), a persistent environmental pollutant, can induce neural tube abnormal development in animals. The possible effects of DBP exposure on human neural tube defects (NTDs) remain elusive. In this study, the distribution of DBP in the body fluid of human NTDs was detected by GC-MS. Then, chick embryos were used to investigate the effects of DBP on early embryonic development. Oxidative stress indicators in chick embryos and the body fluid of human NTDs were detected by ELISA. The cell apoptosis and total reactive oxygen species (ROS) level in chick embryos were detected by whole-mount TUNEL and oxidized DCFDA, respectively. The study found that the detection ratio of positive DBP and its metabolites in maternal urine was higher in the NTD population than that in normal controls. 8-hydroxy-2 deoxyguanosine (8-OHDG) and malondialdehyde (MDA) were evidently upregulated and superoxide dismutase (SOD) was observably downregulated in amniotic fluid and urine. Animal experiments indicated that DBP treatment induced developmental toxicity in chick embryos by enhancing the levels of oxidative stress and cell apoptosis. MDA was increased and SOD was decreased in DBP-treated embryos. Interestingly, the supplement of high-dose choline (100 µg/µL), not folic acid, could partially restore the teratogenic effects of DBP. Our data collectively suggest that the incidence of NTDs is closely associated with DBP exposure. This study may provide new insight for NTD prevention.


Assuntos
Galinhas/metabolismo , Colina/metabolismo , Dibutilftalato/toxicidade , Desenvolvimento Embrionário/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Defeitos do Tubo Neural/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Líquidos Corporais/metabolismo , Embrião de Galinha , Galinhas/crescimento & desenvolvimento , Dibutilftalato/urina , Poluentes Ambientais/urina , Feminino , Ácido Fólico/metabolismo , Humanos , Exposição Materna/efeitos adversos , Teratogênese/efeitos dos fármacos
11.
Mol Med Rep ; 20(2): 1479-1487, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31257471

RESUMO

Alzheimer's disease (AD) is one of the most common forms of dementia. AD is a chronic syndrome of the central nervous system that causes a decline in cognitive function and language ability. Cholinergic deficiency is associated with AD, and various cholinesterase inhibitors have been developed for the treatment of AD, including naturally­derived inhibitors, synthetic analogues and hybrids. Currently, the available drugs for AD are predominantly cholinesterase inhibitors. However, the efficacy of these drugs is limited as they may cause adverse side effects and are not able to completely arrest the progression of the disease. Since AD is multifactorial disease, dual and multi­target inhibitors have been developed. The clinical applications and the limitations of the inhibitors used to treat AD are discussed in the present review. Additionally, this review presents the current status and future directions for the development of novel drugs with reduced toxicity and preserved pharmacological activity.


Assuntos
Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Colina/metabolismo , Inibidores da Colinesterase/síntese química , Nootrópicos/síntese química , Doença de Alzheimer/enzimologia , Doença de Alzheimer/fisiopatologia , Animais , Inibidores da Colinesterase/classificação , Inibidores da Colinesterase/uso terapêutico , Cognição/efeitos dos fármacos , Cognição/fisiologia , Modelos Animais de Doenças , Progressão da Doença , Humanos , Nootrópicos/classificação , Nootrópicos/uso terapêutico
13.
Plant Physiol Biochem ; 142: 211-216, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31302410

RESUMO

Choline is a vital metabolite in plant and synthesized from phosphocholine by phosphocholine phosphatase. The Arabidopsis At1g17710 was identified as the first plant gene encoding the phosphatase for both phosphoethanolamine and phosphocholine (PECP) with much higher catalytic efficiency (>10-fold) for former. In betaine accumulating plants, choline is further required for betaine synthesis. In this report, we found three putative PECP genes in sugar beet, betaine accumulating plants. Two genes encode the proteins of 274 amino acid residues and designated as BvPECP1S and BvPECP2S. Another gene encodes the 331 amino acid protein (BvPECP2L) consisted of BvPECP2S with extra C-terminal amino acid. Enzymatic assays of BvPECP1S revealed that BvPECP1S exhibited the phosphatase activity for both phosphoethanolamine and phosphocholine with higher affinity (>1.8-fold) and catalytic efficiency (>2.64-fold) for phosphocholine. BvPECP2L exhibited low activity. RT-PCR experiments for BvPECP1S showed the increased expression in young leaf and root tip under salt-stress whereas the increased expression in all organs under phosphate deficiency. The expression level of BvPECP2L in salt stressed young leaf and root tip was induced by phosphate deficient. Physiological roles of BvPECP1S and BvPECP2L for the betaine synthesis were discussed.


Assuntos
Beta vulgaris/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Proteínas de Plantas/metabolismo , Beta vulgaris/enzimologia , Beta vulgaris/genética , Beta vulgaris/fisiologia , Colina/metabolismo , Etanolaminas/metabolismo , Regulação da Expressão Gênica de Plantas , Genes de Plantas/genética , Monoéster Fosfórico Hidrolases/genética , Filogenia , Proteínas de Plantas/genética , Proteínas Recombinantes , Estresse Salino , Alinhamento de Sequência
14.
Food Chem ; 293: 418-428, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31151630

RESUMO

Traditional methods evaluating fish quality do not involve comprehensive qualification and quantification of quality-related components. The objective of this study was to investigate the effect of vacuum impregnated fish gelatin (FG) and grape seed extract (GSE) on metabolites of tilapia fillets during storage using nuclear magnetic resonance (NMR). Totally 42 metabolites were identified, 36 of which were quantified. The multivariate analysis results demonstrated distinct separations between fresh and stored fillets, indicating significant metabolite changes during storage. Some metabolites like choline and trimethylamine oxide were closely related to freshness while organic acids were associated with spoilage. Combined FG and GSE reduced the formation of undesirable metabolites like trimethylamine and histidine significantly (P < 0.05). Traditional freshness indexes indicated preserved quality after combined coating and further verified NMR results. This study reveals the potential of NMR to analyse metabolites that determine fish quality and to monitor their changes during storage.


Assuntos
Ciclídeos/metabolismo , Produtos Pesqueiros , Armazenamento de Alimentos , Gelatina/química , Extrato de Sementes de Uva/química , Animais , Colina/metabolismo , Histidina/metabolismo , Espectroscopia de Ressonância Magnética , Metilaminas/metabolismo , Análise Multivariada , Vácuo
15.
Poult Sci ; 98(11): 5661-5668, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31222319

RESUMO

The purpose of the current study was to investigate the effect of choline as a means of increasing docosahexaenoic acid (22:6 n-3, DHA) deposition in egg yolks of hens fed a high-DHA microalgae product. Fifty-six, 26-wk-old, White Leghorn hens were kept in individual cages and randomly allocated to 1 of 4 dietary treatments, each with 7 replicate groups of 2 hens (n = 7 per treatment). The experimental diets were corn and soybean meal based, with 0% microalgae (control), 1% microalgae and no additional choline chloride (Alg), and Alg plus choline chloride at 0.1% (Ch0.1) and 0.2% (Ch0.2). The feeding trial lasted 16 wk. The data were fit as a general linear mixed model to generate least square means in response to diet. Variables measured multiple times during the study were fit as repeated measures. Using orthogonal contrasts, Alg was compared to control, and Ch0.1 and Ch0.2 were compared separately to Alg. Ch0.1 increased hen day egg production (P < 0.05) and Haugh unit (P < 0.05), and reduced feed conversion ratio (P < 0.05) compared to Alg, but Ch0.2 did not. Alg increased egg DHA (P < 0.001), phosphatidylethanolamine (P < 0.05), and phosphatidylcholine (P < 0.001) compared to control, but Ch0.1 or Ch0.2 had no effect compared to Alg (P > 0.05). In the liver, Alg increased lipid peroxidation products compared to control (P < 0.01), and Ch0.1 reduced them compared to Alg (P < 0.01). Both Ch0.1 and Ch0.2 increased hepatic concentrations of γ- (P < 0.05; P < 0.001) and α-tocopherol (P < 0.01; P < 0.001), and Ch0.1 increased γ-tocopherol concentration in eggs compared to Alg (P < 0.05). The results from the current study suggest that supplemental choline chloride in hen diets containing microalgae can improve production performance and egg quality, and protect the liver from oxidative stress.


Assuntos
Galinhas/fisiologia , Colina/metabolismo , Ácidos Docosa-Hexaenoicos/análise , Microalgas/química , Óvulo/fisiologia , Estresse Oxidativo , Ração Animal/análise , Animais , Colina/administração & dosagem , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Feminino , Fígado/efeitos dos fármacos , Fígado/metabolismo , Óvulo/química , Óvulo/efeitos dos fármacos , Distribuição Aleatória , Reprodução/efeitos dos fármacos
16.
Food Funct ; 10(6): 3637-3649, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31165837

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is associated with low-grade chronic inflammation and intestinal dysbiosis. In this study, we investigated the potential benefits of sinapine, a rapeseed polyphenol known to exert anti-inflammatory and anti-oxidant effects, on high-fat diet (HFD)-induced NAFLD in C57BL/6 J mice and the underlying mechanisms. Four week-old mice were randomly divided into four groups and fed a low-fat diet (LFD), a HFD, a HFD with common rapeseed oil (HFD + CRO) and a HFD with sinapine in rapeseed oil (HFD + SRO) for 12 weeks. Supplementation with sinapine reduced the body weight of HFD mice by 10.99%, and decreased the levels of TG and LDL-C by 15.67% and 73.62%, respectively. In addition, sinapine also suppressed the intestinal NF-κB and TNF-α expressions and enhanced the adipose tissue IRS-1 expression in the HFD mice (P < 0.05). In terms of effects on the gut microbiota, sinapine induced a decrease in the ratio of Firmicutes to Bacteroidetes and increased the abundance of probiotics, such as Lactobacillaceae, Akkermansiaceae and Blautia, along with metabolite short-chain fatty acid (SCFA)-mediated upregulation of G protein-coupled receptor 43 (GPR43) to inhibit expression of inflammatory factors. Our collective results strongly supported the fact that the utility of sinapine as a prebiotic agent could prevent gut dysbiosis and obesity-related chronic diseases, such as insulin resistance (IR) and NAFLD.


Assuntos
Colina/análogos & derivados , Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica/dietoterapia , Óleo de Brassica napus/metabolismo , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Brassica napus/química , Colina/metabolismo , Dieta Hiperlipídica/efeitos adversos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/genética , NF-kappa B/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/microbiologia
17.
J Agric Food Chem ; 67(27): 7748-7754, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31203621

RESUMO

Choline and its metabolites have diverse and important functions in many physiological processes, especially for anabolic metabolism in growth and reproduction. Besides endogenous biosynthesis and direct choline supplement, choline esters in the diet are another source of choline in the body. Phenolic choline esters are a group of unique dietary choline esters rich in the seeds of Brassicaceae plants, among which sinapine is a choline ester of sinapic acid abundant in rapeseed. In this study, 40 nursery pigs were fed with rapeseed-derived feed ingredients (RSF) or soybean meal for 3 weeks (20 pigs/diet). The metabolic fate of sinapine-derived choline in RSF was examined by comparing the distribution of choline and its metabolites in digesta, liver, and serum samples by liquid chromatography-mass spectrometry analysis. The results showed that choline was released from extensive hydrolysis of sinapine in the small intestine. However, sinapine-derived choline did not increase the levels of choline and its major metabolites, including betaine, phosphocholine, and glycerophosphocholine, in the liver and serum. Instead, RSF feeding increased trimethylamine (TMA), the microbial metabolite of choline, in the large intestine and further increased trimethylamine N-oxide (TMAO), the oxidation metabolite of TMA, in the liver and serum. Overall, these results suggested that sinapine-derived choline from rapeseed feeding had limited influences on the post-absorption choline pool as a result of its low bioavailability but may serve as a major source of TMAO through microbial metabolism in nursery pigs. Improving the bioavailability of sinapine-derived choline might have the potential to modify the nutritional values and functionalities of rapeseed meal in swine feeding.


Assuntos
Brassica rapa/química , Colina/análogos & derivados , Colina/análise , Dieta/veterinária , Metilaminas/sangue , Sus scrofa/sangue , Ração Animal/análise , Animais , Disponibilidade Biológica , Colina/sangue , Colina/química , Colina/metabolismo , Colina/farmacocinética , Microbioma Gastrointestinal/fisiologia , Hidrólise , Fígado/química , Masculino
18.
Microbiol Spectr ; 7(3)2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31172911

RESUMO

Streptococcus pneumoniae has a complex cell wall that plays key roles in cell shape maintenance, growth and cell division, and interactions with components of the human host. The peptidoglycan has a heterogeneous composition with more than 50 subunits (muropeptides)-products of several peptidoglycan-modifying enzymes. The amidation of glutamate residues in the stem peptide is needed for efficient peptide cross-linking, and peptides with a dipeptide branch prevail in some beta-lactam-resistant strains. The glycan strands are modified by deacetylation of N-acetylglucosamine residues and O-acetylation of N-acetylmuramic acid residues, and both modifications contribute to pneumococcal resistance to lysozyme. The glycan strands carry covalently attached wall teichoic acid and capsular polysaccharide. Pneumococci are unique in that the wall teichoic acid and lipoteichoic acid contain the same unusually complex repeating units decorated with phosphoryl choline residues, which anchor the choline-binding proteins. The structures of lipoteichoic acid and the attachment site of wall teichoic acid to peptidoglycan have recently been revised. During growth, pneumococci assemble their cell walls at midcell in coordinated rounds of cell elongation and division, leading to the typical ovococcal cell shape. Cell wall growth depends on the cytoskeletal FtsA and FtsZ proteins and is regulated by several morphogenesis proteins that also show patterns of dynamic localization at midcell. Some of the key regulators are phosphorylated by StkP and dephosphorylated by PhpP to facilitate robust selection of the division site and plane and to maintain cell shape.


Assuntos
Parede Celular/química , Parede Celular/metabolismo , Streptococcus pneumoniae/química , Streptococcus pneumoniae/metabolismo , Acetilação , Acetilglucosamina/metabolismo , Proteínas de Bactérias/metabolismo , Ciclo Celular , Divisão Celular , Colina/metabolismo , Proteínas do Citoesqueleto , Humanos , Lipopolissacarídeos , Ácidos Murâmicos , Muramidase , Óperon , Resistência às Penicilinas , Peptidoglicano/biossíntese , Peptidoglicano/química , Fosforilação , Polissacarídeos , Ácidos Teicoicos , Resistência beta-Lactâmica
19.
Chem Biol Interact ; 308: 350-356, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31173753

RESUMO

Activation of human butyrylcholinesterase by small quaternary ammonium ions is known. Here, additional ligands in this series are presented: edrophonium and choline, and the reactivator pyridine-2-aldoxime methochloride. Kinetic analysis of the progress curves with these compounds indicates the mechanism of enhanced deacylation by the ligand bound to the catalytic anionic site (Trp82) at the base of the active site. The larger, bis-quaternary ligands examined, as propidium, hexamethonium, decamethonium, and bis-thiocholine, show only competitive inhibition of butyrylcholinesterase, by preventing substrate approach. This hypothesis of enhanced deacylation was tested for reactivation of methanesulfonylfluoride-inactivated butyrylcholinesterase, a complex analogous to organophosphate-aged cholinesterases. The combination of substrate/products and pyridine-2-aldoxime methochloride improved butyrylcholinesterase activity over 2 h of continuous measurements, before which time substrate depletion prevailed. Similar reactivation of Torpedo californica acetylcholinesterase was unsuccessful, but both of these cholinesterases regain some activity if they have been inhibited and aged for days by diisopropylfluorophosphate.


Assuntos
Butirilcolinesterase/metabolismo , Inibidores da Colinesterase/metabolismo , Oximas/metabolismo , Butirilcolinesterase/química , Domínio Catalítico , Colina/química , Colina/metabolismo , Inibidores da Colinesterase/química , Edrofônio/química , Edrofônio/metabolismo , Humanos , Cinética , Ligantes , Oximas/química , Especificidade por Substrato
20.
New Phytol ; 223(4): 1904-1917, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31087404

RESUMO

Choline kinase catalyzes the initial reaction step of choline metabolism that produces phosphocholine, a prerequisite for the biosynthesis of a primary phospholipid phosphatidylcholine. However, the primary choline kinase and its role in plant growth remained elusive in seed plants. Here, we showed that Arabidopsis CHOLINE/ETHANOLAMINE KINASE 1 (CEK1) encodes functional CEK that prefers choline than ethanolamine as a substrate in vitro and affects contents of choline and phosphocholine but not phosphatidylcholine in vivo. CEK1 is localized at endoplasmic reticulum (ER); upon tunicamycin-induced ER stress, a null mutant of CEK1 showed hypersensitive phenotype in seedlings, albeit with no enhanced choline kinase activity. Our results demonstrate that CEK1 is a primary ER-localized choline kinase in vivo that is required for ER stress tolerance possibly through the modulation of choline metabolites.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimologia , Estresse do Retículo Endoplasmático , Retículo Endoplasmático/enzimologia , Arabidopsis/efeitos dos fármacos , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/genética , Colina/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Marcadores Genéticos , Análise do Fluxo Metabólico , Mutação/genética , Especificidade de Órgãos/efeitos dos fármacos , Fenótipo , Plântula/efeitos dos fármacos , Especificidade por Substrato/efeitos dos fármacos , Tunicamicina/farmacologia , Resposta a Proteínas não Dobradas/efeitos dos fármacos
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