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1.
Mol Genet Genomics ; 299(1): 43, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38598031

RESUMEN

Phosphatidylserine (PS) is important for maintaining growth, cytoskeleton, and various functions in yeast; however, its role in stress responses is poorly understood. In Schizosaccharomyces pombe, the PS synthase deletion (pps1∆) mutant shows defects in growth, morphology, cytokinesis, actin cytoskeleton, and cell wall integrity, and these phenotypes are rescued by ethanolamine supplementation. Here, we evaluated the role of Pps1 in the salt stress response in S. pombe. We found that pps1∆ cells are sensitive to salt stresses such as KCl and CaCl2 even in the presence of ethanolamine. Loss of the functional cAMP-dependent protein kinase (git3∆ or pka1∆) or phospholipase B Plb1 (plb1∆) enhanced the salt stress-sensitive phenotype in pps1∆ cells. Green fluorescent protein (GFP)-Pps1 was localized at the plasma membrane and endoplasmic reticulum regardless of the stress conditions. In pka1∆ cells, GFP-Pps1 was accumulated around the nucleus under the KCl stress. Pka1 was localized in the nucleus and the cytoplasm under normal conditions and transferred from the nucleus to the cytoplasm under salt-stress conditions. Pka1 translocated from the nucleus to the cytoplasm during CaCl2 stress in the wild-type cells, while it remained localized in the nucleus in pps1∆ cells. Expression and phosphorylation of Pka1-GFP were not changed in pps1∆ cells. Our results demonstrate that Pps1 plays an important role in the salt stress response in S. pombe.


Asunto(s)
Schizosaccharomyces , Schizosaccharomyces/genética , CDPdiacilglicerol-Serina O-Fosfatidiltransferasa/genética , Cloruro de Calcio , Estrés Salino/genética , Etanolamina , Etanolaminas , Proteínas Fluorescentes Verdes
2.
Redox Biol ; 66: 102874, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37683300

RESUMEN

OBJECTIVE: Enhancing energy turnover via uncoupled mitochondrial respiration in adipose tissue has great potential to improve human obesity and other metabolic complications. However, the amount of human brown adipose tissue and its uncoupling protein 1 (UCP1) is low in obese patients. Recently, a class of endogenous molecules, N-acyl amino acids (NAAs), was identified as mitochondrial uncouplers in murine adipocytes, presumably acting via the adenine nucleotide translocator (ANT). Given the translational potential, we investigated the bioenergetic effects of NAAs in human adipocytes, characterizing beneficial and adverse effects, dose ranges, amino acid derivatives and underlying mechanisms. METHOD: NAAs with neutral (phenylalanine, leucine, isoleucine) and polar (lysine) residues were synthetized and assessed in intact and permeabilized human adipocytes using plate-based respirometry. The Seahorse technology was applied to measure bioenergetic parameters, dose-dependency, interference with UCP1 and adenine nucleotide translocase (ANT) activity, as well as differences to the established chemical uncouplers niclosamide ethanolamine (NEN) and 2,4-dinitrophenol (DNP). RESULT: NAAs with neutral amino acid residues potently induce uncoupled respiration in human adipocytes in a dose-dependent manner, even in the presence of the UCP1-inhibitor guanosine diphosphate (GDP) and the ANT-inhibitor carboxyatractylate (CAT). However, neutral NAAs significantly reduce maximal oxidation rates, mitochondrial ATP-production, coupling efficiency and reduce adipocyte viability at concentrations above 25 µM. The in vitro therapeutic index (using induced proton leak and viability as determinants) of NAAs is lower than that of NEN and DNP. CONCLUSION: NAAs are potent mitochondrial uncouplers in human adipocytes, independent of UCP1 and ANT. However, previously unnoticed adverse effects harm adipocyte functionality, reduce the therapeutic index of NAAs in vitro and therefore question their suitability as anti-obesity agents without further chemical modifications.


Asunto(s)
Adipocitos , Aminoácidos , Humanos , Animales , Ratones , Etanolamina , Tejido Adiposo Pardo , Metabolismo Energético
3.
Molecules ; 28(9)2023 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-37175104

RESUMEN

Unhealthy dietary habits have been identified as a risk factor for the development and progression of cancer. Therefore, adopting a healthy eating pattern is currently recommended to prevent the onset of different types of cancers, including breast carcinoma. In particular, the Mediterranean diet, based on high consumption of omega-3 polyunsaturated fatty acids (N-3 PUFAs), such as those found in cold-water fish and other seafood, nuts, and seeds, is recommended to reduce the incidence of several chronic-degenerative diseases. Indeed, the consumption of N-3 PUFAs, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), reduced the risk of different types of cancer, including breast cancer. Moreover, they can counteract breast cancer progression and reduce the side effects of chemotherapy in breast cancer survival. Studies have demonstrated that DHA, exhibiting greater antitumor activity than EPA in breast cancer, can be attributed to its direct impact on breast cancer cells and also due to its conversion into various metabolites. N-docosahexaenoyl ethanolamine, DHEA, is the most studied DHA derivative for its therapeutic potential in breast cancer. In this review, we emphasize the significance of dietary habits and the consumption of N-3 polyunsaturated fatty acids, particularly DHA, and we describe the current knowledge on the antitumoral action of DHA and its derivative DHEA in the treatment of breast cancer.


Asunto(s)
Ácidos Grasos Omega-3 , Neoplasias , Animales , Etanolamina/uso terapéutico , Ácidos Docosahexaenoicos/farmacología , Ácidos Docosahexaenoicos/uso terapéutico , Ácido Eicosapentaenoico/farmacología , Deshidroepiandrosterona , Neoplasias/tratamiento farmacológico
4.
Drug Des Devel Ther ; 17: 579-595, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36855515

RESUMEN

Purpose: To study the efficacy of Qianshan Huoxue Gao (QS) in treating acute coronary syndrome (ACS) and to explore the mechanism of action from the perspective of intestinal flora regulation. Methods: Male Sprague-Dawley rats were divided into control, model, QS, and atorvastatin groups; except for the control group, rats underwent ligation of the left anterior descending branch of the coronary artery. Following treatment for 28 days, cardiac function was evaluated using an echocardiographic assay; ELISAs for serum creatine kinase isoenzyme (CK-MB), cardiac troponin I (cTnI), high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-2 (IL-2), IL-6, and tumor necrosis factor-α (TNF-α); assessment of cardiac enzymes and inflammatory response; hematoxylin and eosin (HE) staining for histopathological changes in the heart, skin, and viscera; 16S rRNA gene sequencing for intestinal flora diversity and structural differences analysis; and we further investigated intestinal contents using metabolomics. Results: Compared with controls, CK-MB and cTnI were increased (P<0.01); ejection factor and fractional shortening were decreased (P<0.01); left ventricular internal end-diastolic dimension and left ventricular internal end-systolic dimension were increased (P<0.01); and IL-2, IL-6, TNF-α, and hs-CRP were increased in the model group. Myocardial damage and inflammation were also observed by HE staining. QS improved these indexes, similar to the atorvastatin group; therefore, QS could effectively treat ACS. QS modulates the structure and abundance of the intestinal flora in ACS model rats, among which Bacteroides, Lactobacillus, and Rikenellaceae_RC9_gut_group are associated with cardiovascular disease. Metabolomics revealed that the intestinal metabolite content changed in ACS, with ethanolamine (EA) being the most relevant metabolite for ACS treatment by QS. EA was significantly positively correlated with Eubacterium xylanophilum group, Ruminococcus, unclassified f__Oscillospiraceae, Intestinimonas, Eubacterium siraeum group, Lachnospiraceae NK4A136 group, and norank f__Desulfovibrionaceae. Conclusion: QS can effectively treat ACS and can restore regulation of the intestinal flora. EA may be the primary metabolite of QS, exerting a therapeutic effect in ACS.


Asunto(s)
Síndrome Coronario Agudo , Microbioma Gastrointestinal , Masculino , Animales , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa , Interleucina-2 , Atorvastatina , Proteína C-Reactiva , Interleucina-6 , ARN Ribosómico 16S , Etanolamina , Etanolaminas
5.
Int J Mol Sci ; 22(20)2021 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-34681834

RESUMEN

The selenoprotein family includes 25 members, many of which are antioxidant or redox regulating enzymes. A unique member of this family is Selenoprotein I (SELENOI), which does not catalyze redox reactions, but instead is an ethanolamine phosphotransferase (Ept). In fact, the characteristic selenocysteine residue that defines selenoproteins lies far outside of the catalytic domain of SELENOI. Furthermore, data using recombinant SELENOI lacking the selenocysteine residue have suggested that the selenocysteine amino acid is not directly involved in the Ept reaction. SELENOI is involved in two different pathways for the synthesis of phosphatidylethanolamine (PE) and plasmenyl PE, which are constituents of cellular membranes. Ethanolamine phospholipid synthesis has emerged as an important process for metabolic reprogramming that occurs in pluripotent stem cells and proliferating tumor cells, and this review discusses roles for upregulation of SELENOI during T cell activation, proliferation, and differentiation. SELENOI deficiency lowers but does not completely diminish de novo synthesis of PE and plasmenyl PE during T cell activation. Interestingly, metabolic reprogramming in activated SELENOI deficient T cells is impaired and this reduces proliferative capacity while favoring tolerogenic to pathogenic phenotypes that arise from differentiation. The implications of these findings are discussed related to vaccine responses, autoimmunity, and cell-based therapeutic approaches.


Asunto(s)
Etanolamina/metabolismo , Etanolaminofosfotransferasa/fisiología , Activación de Linfocitos , Fosfolípidos/metabolismo , Selenoproteínas/fisiología , Linfocitos T/fisiología , Reprogramación Celular , Humanos , Fosfatidiletanolaminas/metabolismo , Selenio/metabolismo , Selenocisteína/metabolismo , Selenoproteínas/química , Regulación hacia Arriba
6.
Biomolecules ; 10(2)2020 02 12.
Artículo en Inglés | MEDLINE | ID: mdl-32059524

RESUMEN

Kynurenine (kyn) and kynurenic acid (kyna) are well-defined metabolites of tryptophan catabolism collectively known as "kynurenines", which exert regulatory functions in host-microbiome signaling, immune cell response, and neuronal excitability. Kynurenine containing peptides endowed with opioid receptor activity have been isolated from natural organisms; thus, in this work, novel opioid peptide analogs incorporating L-kynurenine (L-kyn) and kynurenic acid (kyna) in place of native amino acids have been designed and synthesized with the aim to investigate the biological effect of these modifications. The kyna-containing peptide (KA1) binds selectively the m-opioid receptor with a Ki = 1.08 ± 0.26 (selectivity ratio m/d/k = 1:514:10000), while the L-kyn-containing peptide (K6) shows a mixed binding affinity for m, d, and k-opioid receptors, with efficacy and potency (Emax = 209.7 + 3.4%; LogEC50 = -5.984 + 0.054) higher than those of the reference compound DAMGO. This novel oligopeptide exhibits a strong antinociceptive effect after i.c.v. and s.c. administrations in in vivo tests, according to good stability in human plasma (t1/2 = 47 min).


Asunto(s)
Quinurenina/química , Oligopéptidos/química , Receptores Opioides/agonistas , Animales , Encéfalo/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Ésteres/química , Etanolamina/química , Femenino , Formaldehído/química , Proteínas de Unión al GTP/química , Cobayas , Humanos , Ácido Quinurénico/química , Masculino , Oligopéptidos/farmacocinética , Unión Proteica , Ratas , Ratas Wistar , Receptores Opioides mu/química , Triptófano/metabolismo
7.
J Med Food ; 23(3): 319-325, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31928490

RESUMEN

Oxidative stress and lipid peroxidation are considered key factors linking obesity with its associated complications. Epigallo catechin-3-gallate (EGCG) and oleoylethanolamide, together with its phospholipid precursor N-oleoyl-phosphatidylethanolamine (NOPE), are nutritional compounds that might improve the oxidative stress status of obese people. Unfortunately, the bioavailability of these compounds is low; however, the coadministration of NOPE with EGCG has been shown to ameliorate both the plasma availability of EGCG and the intestinal levels of NOPE in rats. This double-blind placebo-controlled study investigated the effects of 2 months' supplementation with EGCG complexed with NOPE, combined with moderate energy restriction, on plasma oxidative status of overweight and class I obese subjects. A total of 138 subjects (body mass index: 25-35 kg/m2) were recruited and randomized into two groups: the first (n = 67) received caps of placebo and the second (n = 71) caps of an oily dispersion of EGCG complexed with NOPE for 2 months. Subjects' supplementation was combined with moderate energy restriction (-800 kcal/day). Plasma oxidative status was determined by measuring the levels of oxidized low-density lipoprotein (Ox-LDL), malondialdehyde and reactive oxygen metabolites, and by calculating the lag time and the slope of Cu-induced lipid peroxidation kinetics. In total 116 subjects (27 M/89 F) completed the supplementation period, 49 in the placebo group and 67 in the treated group. Treatment induced a similar significant weight reduction in the two groups. Moreover, we found the mean changes of Ox-LDL significantly lower and the mean changes of antioxidant capacity (lag time) significantly higher in NOPE-EGCG group than in placebo group (treatment effect mean difference: -3.15 UL, P < .044 and +5.37 min, P < .0347, respectively). EGCG plasma levels were detectable only after 2 months of NOPE-EGCG diet. The NOPE-EGCG integration to a low-energy diet seems, therefore, useful for ameliorating oxidative stress-related markers, which are concomitant causes of obesity-induced disorders.


Asunto(s)
Catequina/análogos & derivados , Etanolamina/administración & dosificación , Obesidad/dietoterapia , Obesidad/tratamiento farmacológico , Sobrepeso/dietoterapia , Sobrepeso/tratamiento farmacológico , Adulto , Índice de Masa Corporal , Restricción Calórica , Catequina/administración & dosificación , Suplementos Dietéticos/análisis , Método Doble Ciego , Etanolamina/química , Femenino , Humanos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Persona de Mediana Edad , Obesidad/genética , Obesidad/metabolismo , Sobrepeso/metabolismo , Estrés Oxidativo/efectos de los fármacos
8.
Microb Pathog ; 119: 200-207, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29654901

RESUMEN

Clostridium perfringens possesses the ethanolamine (EA) utilization (eut) system encoded within the eut operon, which utilizes the EA as a carbon, nitrogen and energy source. To determine the role of the eut system in C. perfringens growth, an in-frame deletion of the eutABC genes was made in strain HN13 to generate the eutABC-deleted mutant strain HY1701. Comparison of HN13 and HY1701 growth in media supplemented with 1.0% glucose and/or 1.0% EA showed that glucose enhanced the growth of both strains, whereas EA enhanced HN13 growth, but not that of HY1701, indicating that the eut system is necessary for C. perfringens to utilize EA. The two-component regulatory system EutVW is needed to induce eut gene expression in response to EA whereas the global virulence regulator VirRS differentially controlled eut gene expression depending on glucose and EA availability. To assess the role of the eut system in vivo, an equal number of HN13 and HY1701 cells were injected into the right thigh muscles of mice. Mice infected with HY1701 showed fewer symptoms than those injected with HN13. The mortality rate of mice infected with HY1701 tended to be lower than for mice infected with HN13. In addition, in infected tissues from mice injected with a mixture of HN13 and HY1701, HN13 outnumbered HY1701. PCR screening demonstrated that C. perfringens isolated from gas gangrene and sporadic diarrhea cases carried both eut genes and the perfringolysin O gene (pfoA) as well as the phospholipase C gene (plc). However, pfoA was not detected in isolates from food poisoning patients and healthy volunteers. Culture supernatants prepared from HN13 grown in media containing 7.5% sheep red blood cells induced significantly higher eutB expression levels compared to those from plc- and/or pfoA-deletion mutants. Together, these results indicate that the eut system plays a nutritional role for C. perfringens during histolytic infection.


Asunto(s)
Clostridium perfringens/crecimiento & desarrollo , Clostridium perfringens/metabolismo , Clostridium perfringens/patogenicidad , Etanolamina/metabolismo , Gangrena Gaseosa/metabolismo , Animales , Toxinas Bacterianas/genética , Clostridium perfringens/genética , Modelos Animales de Enfermedad , Enfermedades Transmitidas por los Alimentos/microbiología , Regulación Bacteriana de la Expresión Génica , Genes Bacterianos/genética , Proteínas Hemolisinas/genética , Humanos , Hidroxocobalamina/antagonistas & inhibidores , Masculino , Ratones , Mortalidad , Operón , Eliminación de Secuencia , Ovinos , Fosfolipasas de Tipo C/genética , Virulencia
9.
Reprod Toxicol ; 78: 102-110, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29635045

RESUMEN

Ethanolamine (EA) reduced implantation success in a two-generation reproduction toxicity study; the aim of this work was to explore the underlying basis for this response. When administered to pregnant rats during gestation days (GD) 1-3, 4-5, or 6-7, EA had no effect upon implantation success. In a second experiment, EA was administered either in the diet or by oral gavage from two weeks prior to mating through to GD 8. Parallel groups also received a diet supplemented with choline. In the absence of supplementary choline, EA induced early resorptions, statistically significant only when administered in the diet. A slight reduction in implantation success was ameliorated by supplementary choline. We conclude that implantation is affected by EA only when exposure starts before mating; that dietary administration is more effective than gavage dosing; and that interference with choline homeostasis may play a role in the aetiology of this lesion.


Asunto(s)
Colina/farmacología , Suplementos Dietéticos , Implantación del Embrión/efectos de los fármacos , Etanolamina/toxicidad , Animales , Femenino , Masculino , Embarazo , Ratas Wistar
10.
J Oleo Sci ; 66(7): 659-665, 2017 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-28626133

RESUMEN

A simple method for incorporating amine groups in hydrogenated castor oil (HCO) to produce wax for beeswax or carnauba wax substitution in packaging and coating was developed. From the conversion rate of the products, HCO was reacted with ethanolamine at 150°C for 5 h, and the molar ratio of HCO and ethanolamine was 1:4. The hardness of the final product was seven times higher than that of beeswax, the cohesiveness of the final product was 1.3 times higher than that of beeswax and approximately one half of that of carnauba wax, and the melting point of the final product is 98°C. The Fourier transform Infrared spectroscopy showed that the amide groups were incorporated to form the amide products. In coating application, the results showed that the force of the final product coating cardboard was higher than that of beeswax and paraffin wax and less than that of carnauba wax. After 24 h soaking, the compression forces were decreased. HCO fatty acid wax can be an alternative wax for carnauba wax and beeswax in coating applications.


Asunto(s)
Amidas/síntesis química , Aceite de Ricino/análogos & derivados , Fenómenos Químicos , Técnicas de Química Sintética/métodos , Etanolamina/química , Ceras/síntesis química , Aceite de Ricino/química , Calor , Hidrogenación , Espectroscopía Infrarroja por Transformada de Fourier , Factores de Tiempo
11.
BMC Med ; 15(1): 56, 2017 03 16.
Artículo en Inglés | MEDLINE | ID: mdl-28298227

RESUMEN

BACKGROUND: Pancreatic adenocarcinomas (PAs) have very poor prognoses even when surgery is possible. Currently, there are no tissular biomarkers to predict long-term survival in patients with PA. The aims of this study were to (1) describe the metabolome of pancreatic parenchyma (PP) and PA, (2) determine the impact of neoadjuvant chemotherapy on PP and PA, and (3) find tissue metabolic biomarkers associated with long-term survivors, using metabolomics analysis. METHODS: 1H high-resolution magic angle spinning (HRMAS) nuclear magnetic resonance (NMR) spectroscopy using intact tissues was applied to analyze metabolites in PP tissue samples (n = 17) and intact tumor samples (n = 106), obtained from 106 patients undergoing surgical resection for PA. RESULTS: An orthogonal partial least square-discriminant analysis (OPLS-DA) showed a clear distinction between PP and PA. Higher concentrations of myo-inositol and glycerol were shown in PP, whereas higher levels of glucose, ascorbate, ethanolamine, lactate, and taurine were revealed in PA. Among those metabolites, one of them was particularly obvious in the distinction between long-term and short-term survivors. A high ethanolamine level was associated with worse survival. The impact of neoadjuvant chemotherapy was higher on PA than on PP. CONCLUSIONS: This study shows that HRMAS NMR spectroscopy using intact tissue provides important and solid information in the characterization of PA. Metabolomics profiling can also predict long-term survival: the assessment of ethanolamine concentration can be clinically relevant as a single metabolic biomarker. This information can be obtained in 20 min, during surgery, to distinguish long-term from short-term survival.


Asunto(s)
Adenocarcinoma/metabolismo , Quimioterapia Adyuvante/métodos , Etanolamina/metabolismo , Metabolómica/métodos , Páncreas , Neoplasias Pancreáticas/metabolismo , Adenocarcinoma/patología , Adenocarcinoma/terapia , Anciano , Biomarcadores/metabolismo , Análisis Discriminante , Femenino , Humanos , Espectroscopía de Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Páncreas/metabolismo , Páncreas/patología , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/terapia , Pronóstico , Sobrevivientes/estadística & datos numéricos , Resultado del Tratamiento , Neoplasias Pancreáticas
12.
PLoS One ; 12(1): e0169742, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28125641

RESUMEN

BACKGROUND: Phytoestrogens such as genistein, the most prominent isoflavone from soy, show concentration-dependent anti-estrogenic or estrogenic effects. High genistein concentrations (>10 µM) also promote proliferation of bone cancer cells in vitro. On the other hand, the most active component of the vitamin D family, calcitriol, has been shown to be tumor protective in vitro and in vivo. The purpose of this study was to examine a putative synergism of genistein and calcitriol in two osteosarcoma cell lines MG-63 (early osteoblast), Saos-2 (mature osteoblast) and primary osteoblasts. METHODS: Thus, an initial screening based on cell cycle phase alterations, estrogen (ER) and vitamin D receptor (VDR) expression, live cell metabolic monitoring, and metabolomics were performed. RESULTS: Exposure to the combination of 100 µM genistein and 10 nM calcitriol reduced the number of proliferative cells to control levels, increased ERß and VDR expression, and reduced extracellular acidification (40%) as well as respiratory activity (70%), primarily in MG-63 cells. In order to identify the underlying cellular mechanisms in the MG-63 cell line, metabolic profiling via GC/MS technology was conducted. Combined treatment significantly influenced lipids and amino acids preferably, whereas metabolites of the energy metabolism were not altered. The comparative analysis of the log2-ratios revealed that after combined treatment only the metabolite ethanolamine was highly up-regulated. This is the result: a strong overexpression (350%) of the enzyme sphingosine-1-phosphate lyase (SGPL1), which irreversibly degrades sphingosine-1-phosphate (S1P), thereby, generating ethanolamine. S1P production and secretion is associated with an increased capability of migration and invasion of cancer cells. CONCLUSION: From these results can be concluded that the tumor promoting effect of high concentrations of genistein in immature osteosarcoma cells is reduced by the co-administration of calcitriol, primarily by the breakdown of S1P. It should be tested whether this anti-metastatic pathway can be stimulated by combined treatment also in metastatic xenograft mice models.


Asunto(s)
Aldehído-Liasas/biosíntesis , Calcitriol/administración & dosificación , Receptor beta de Estrógeno/biosíntesis , Genisteína/administración & dosificación , Osteosarcoma/tratamiento farmacológico , Receptores de Calcitriol/biosíntesis , Aldehído-Liasas/genética , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Sinergismo Farmacológico , Receptor beta de Estrógeno/genética , Etanolamina/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Lisofosfolípidos/metabolismo , Ratones , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Osteosarcoma/metabolismo , Osteosarcoma/patología , Fitoestrógenos/administración & dosificación , Receptores de Calcitriol/genética , Esfingosina/análogos & derivados , Esfingosina/metabolismo
13.
Appl Microbiol Biotechnol ; 100(9): 3999-4013, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26691518

RESUMEN

Our screening study yielded a copper amine oxidase (SrAOX) from Syncephalastrum racemosum, which showed much higher affinity and catalytic efficiency toward ethanolamine (EA) than any other amine oxidase (AOX). Following purification of the enzyme to electrophoretic homogeneity from a cell-free extract, the maximum activity toward EA was detected at pH 7.2-7.5 and 45 °C. The SrAOX complementary DNA (cDNA) was composed of a 2052-bp open reading frame encoding a 683-amino acid protein with a molecular mass of 77,162 Da. The enzyme functions as a homodimer. The deduced amino acid sequence of SrAOX showed 55.3 % identity to Rhizopus delemar AOX and contains two consensus sequences of Cu-AOX, NYDY, and HHQH, suggesting SrAOX is a type 1 Cu-AOX (i.e., a topaquinone enzyme). Structural homology modeling showed that residues (112)ML(113), (141)FADTWG(146) M158, and N318 are unique, and T144 possibly characterizes the substrate specificity of SrAOX. The recombinant enzyme (rSrAOX) was produced using Escherichia coli. Steady-state kinetic analysis of rSrAOX activity toward EA (pH 7.5 and 45 °C) gave K m and k cat values of 0.848 ± 0.009 mM and 9.11 ± 0.13 s(-1), respectively. The standard curves were linear between 0.1 and 2 mM EA, and 10 µg mL(-1)-2.5 mg mL(-1) (15 µM-3.6 mM) phosphatidylethanolamine using Streptomyces chromofuscus phospholipase D, respectively, was sufficiently sensitive for clinical use.


Asunto(s)
Amina Oxidasa (conteniendo Cobre)/metabolismo , Etanolamina/metabolismo , Mucorales/enzimología , Amina Oxidasa (conteniendo Cobre)/química , Amina Oxidasa (conteniendo Cobre)/genética , Amina Oxidasa (conteniendo Cobre)/aislamiento & purificación , Secuencia de Aminoácidos , Escherichia coli/genética , Escherichia coli/metabolismo , Concentración de Iones de Hidrógeno , Cinética , Conformación Proteica , Multimerización de Proteína , Proteínas Recombinantes , Análisis de Secuencia de ADN , Homología de Secuencia de Aminoácido , Especificidad por Sustrato , Temperatura
14.
PLoS One ; 9(1): e83501, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24465382

RESUMEN

Benzotriazole and borate derivatives have long been used as multifunctional additives to lubricants. A novel, environmentally friendly additive borate ester (NHB), which contains boron, ethanolamine, and benzotriazole groups in one molecule, was synthesized by a multi-step reaction, and its tribological properties in rapeseed oil (RSO) were investigated by a four-ball tribometer. The hydrolysis stability of the additive was investigated by half-time and open observation methods, and the mechanism of hydrolysis stability was discussed through Gaussian calculation. The novel compound NHB showed excellent performance under extreme pressure, against wearing, and in reducing friction, and its hydrolysis time is more than 1,220 times, which is better than that of triethyl borate. The mass ratio of NHB is bigger than that of the mixed liquid of triethyl borate and ethanolamine. The lone electron of amino N atoms forms a coordination effect with the B atom to compensate for the shortage of electrons in the B atom and to improve the hydrolysis stability of NHB. The surface morphology and the traces of different elements in the tribofilms formed with 1.0 wt.% NHB in were detected with scanning electron microscopy(SEM), energy dispersive X-ray spectroscopy (EDX)and X-ray photoelectron spectroscopy(XPS). The results shown that the additive caused a tribochemical reaction with the steel ball surface during the lubricating process. A mixed boundary lubrication film that contains organic nitrogen and inorganic salts, such as BN, B2O3, FeOx, Fe-O-B, and FeB, was also formed, and the formation of the lubricating film improved the tribological properties of the base oil.


Asunto(s)
Boratos/química , Etanolamina/química , Lubricantes/síntesis química , Triazoles/química , Ésteres , Ácidos Grasos Monoinsaturados , Fricción , Hidrólisis , Lubricantes/química , Microscopía Electrónica de Rastreo , Modelos Químicos , Estructura Molecular , Espectroscopía de Fotoelectrones , Aceites de Plantas/química , Aceite de Brassica napus , Espectrometría por Rayos X
15.
Cell Biochem Biophys ; 67(3): 1353-63, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23743710

RESUMEN

Cadmium (Cd) is a potent toxic element used in several industries and in the process contaminates air, soil, and water. Exposure of Saccharomyces cerevisiae to Cd increases the major phospholipids, and profound increase was observed in phosphatidylethanolamine (PE). In yeast, there are four different pathways contributing to the biosynthesis of PE, and contribution to PE pool through phosphatidylserine decarboxylase2 (psd2) is not significant in normal conditions. Upon Cd exposure, psd2Δ strain showed a significant decrease in major phospholipids including PE. When exposed to Cd, wild-type (WT) cells depicted an increase in ER stress and autophagy, whereas in psd2, ER stress was noted but autophagy process was impaired. The supplementation of ethanolamine did not overcome the Cd stress and also the autophagy process, whereas overexpression of PSD2 in psd2Δ increased the cellular tolerance, PE levels, and the autophagy process against Cd stress. From our studies, we can suggest that PSD2 of S. cerevisiae has an important role in PE synthesis and in autophagy process under Cd stress.


Asunto(s)
Autofagia/fisiología , Cadmio/toxicidad , Carboxiliasas/metabolismo , Fosfatidiletanolaminas/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Estrés Fisiológico/efectos de los fármacos , Aminopeptidasas/genética , Aminopeptidasas/metabolismo , Autofagia/efectos de los fármacos , Carboxiliasas/genética , Etanolamina/farmacología , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/enzimología , Proteínas de Saccharomyces cerevisiae/genética
16.
Br J Pharmacol ; 169(4): 772-83, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23088259

RESUMEN

N-3 Long-chain polyunsaturated fatty acids (n-3 LC-PUFAs), in particular α-linolenic acid (18:3n-3), eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) are receiving much attention because of their presumed beneficial health effects. To explain these, a variety of mechanisms have been proposed, but their interactions with the endocannabinoid system have received relatively little attention so far. However, it has already been shown some time ago that consumption of n-3 LC-PUFAs not only affects the synthesis of prototypic endocannabinoids like anandamide but also stimulates the formation of specific n-3 LC-PUFA-derived conjugates with ethanolamine, dopamine, serotonin or other amines. Some of these fatty amides show overlapping biological activities with those of typical endocannabinoids, whereas others possess distinct and sometimes largely unknown receptor affinities and other properties. The ethanolamine and dopamine conjugates of DHA have been the most investigated thus far. These mediators may provide promising new leads to the field of inflammatory and neurological disorders and for other pharmacological applications, including their use as carrier molecules for neurotransmitters to target the brain. Furthermore, combinations of n-3 LC-PUFA-derived fatty acid amides, their precursors and FAAH inhibitors offer possibilities to optimise their effects in health and disease.


Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Agonistas de Receptores de Cannabinoides/uso terapéutico , Suplementos Dietéticos , Endocannabinoides/uso terapéutico , Ácidos Grasos Omega-3/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Alcamidas Poliinsaturadas/uso terapéutico , Acilación , Animales , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/metabolismo , Agonistas de Receptores de Cannabinoides/química , Agonistas de Receptores de Cannabinoides/metabolismo , Ácidos Docosahexaenoicos/análogos & derivados , Ácidos Docosahexaenoicos/metabolismo , Ácidos Docosahexaenoicos/uso terapéutico , Dopamina/análogos & derivados , Dopamina/metabolismo , Dopamina/uso terapéutico , Sistemas de Liberación de Medicamentos , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/metabolismo , Ácido Eicosapentaenoico/uso terapéutico , Endocannabinoides/química , Endocannabinoides/metabolismo , Etanolamina/química , Etanolamina/metabolismo , Etanolamina/uso terapéutico , Ácidos Grasos Omega-3/química , Ácidos Grasos Omega-3/metabolismo , Aceites de Pescado/química , Peces , Humanos , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/metabolismo , Alcamidas Poliinsaturadas/química , Alcamidas Poliinsaturadas/metabolismo , Receptores de Cannabinoides/química , Receptores de Cannabinoides/metabolismo , Alimentos Marinos/análisis , Ácido alfa-Linolénico/análogos & derivados , Ácido alfa-Linolénico/metabolismo , Ácido alfa-Linolénico/uso terapéutico
17.
J Chem Ecol ; 38(12): 1552-60, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23179101

RESUMEN

The cowpea aphid Aphis craccivora that infests the black locust Robinia pseudoacacia shows toxicity to its predator, the multicolored Asian ladybird beetle, Harmonia axyridis. In contrast, the same aphid species that infests the common vetch, Vicia angustifolia, is suitable prey for H. axyridis larvae. Previously, it was reported that the toxicity of A. craccivora infesting R. pseudoacacia was due to canavanine and 2-aminoethanol, but there was some doubt about the toxicity of these compounds and their concentrations in the aphids. In the present study, we determined the concentrations of cyanamide, canavanine, and 2-aminoethanol in A. craccivora infesting the two host plants. In the extracts of A. craccivora that infested either of the host plants, canavanine was undetectable, and 2-aminoethanol was detected at the concentration of 3.0-4.0 µg/g fresh weight. Cyanamide was detected in the extract of A. craccivora that infested R. pseudoacacia (7.7 µg/g fresh weight) but not in that infesting V. angustifolia. The toxicity of canavanine, 2-aminoethanol, and cyanamide was evaluated against H. axyridis larvae in a bioassay by using an artificial diet containing these compounds at various concentrations. Cyanamide exhibited 10-100 times stronger toxicity than canavanine and 2-aminoethanol. These results indicate that the toxicity is at least partly due to cyanamide, which is present in the toxic A. craccivora that infests R. pseudoacacia but absent from the non-toxic A. craccivora that infests V. angustifolia.


Asunto(s)
Áfidos/química , Canavanina/análisis , Escarabajos/fisiología , Cianamida/análisis , Etanolamina/análisis , Robinia/química , Vicia/química , Aminoácidos/química , Animales , Canavanina/toxicidad , Cromatografía Líquida de Alta Presión , Escarabajos/crecimiento & desarrollo , Cianamida/toxicidad , Dieta/veterinaria , Etanolamina/toxicidad , Femenino , Cromatografía de Gases y Espectrometría de Masas , Larva/efectos de los fármacos , Larva/fisiología , Tasa de Supervivencia
18.
Yeast ; 29(10): 443-52, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23027642

RESUMEN

The phospholipid metabolism of Saccharomyces cerevisiae plays a central role in its adaptation to low temperatures. In order to detect the key genes in this adaptation, various phospholipid mutants from the EUROSCARF collection of Saccharomyces cerevisiae BY4742 were tested to ascertain whether the suppression of some genes could improve the fermentation vitality of the cells at low temperature. The cell vitality and phospholipid composition of these mutants were analysed. Some knockouts improved (hmn1Δ) or impaired (cho2Δ and psd1Δ) their vitality at low temperature (13 ° C) but were not affected at optimum temperature (25 ° C). A common trait of the mutants that had some defect in vitality was a lower concentration of phosphatidylcholine and/or phosphatidylethanolamine. The supplementation with choline allowed them to recover viability, probably by synthesis through the Kennedy pathway. Hmn1Δ showed a lower concentration of phosphatidylcholine, which explains the dominant role of the de novo pathway in cellular phosphatidylethanolamine and phosphatidylcholine vs the Kennedy pathway. The absence of such genes as CRD1 or OPI3 produced important changes in phospholipid composition. Cardiolipin was not detected in crd1Δ but phosphatidylglycerol circumvents most of the functions assigned to CL. The considerable reduction in PC diminished the cell vitality of opi3Δ at both temperatures, although the decrease at 13 ° C was more marked.


Asunto(s)
Frío , Etanolamina/metabolismo , Fosfolípidos/metabolismo , Saccharomyces cerevisiae/fisiología , Adaptación Fisiológica , Colina/metabolismo , Técnicas de Inactivación de Genes , Redes y Vías Metabólicas , Viabilidad Microbiana , Mutación , Fenotipo , Fosfatidilcolinas/metabolismo , Fosfatidiletanolaminas/metabolismo , Fosfolípidos/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crecimiento & desarrollo , Factores de Tiempo
19.
ChemSusChem ; 5(9): 1773-7, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22890958

RESUMEN

A simple direct solution coating process for forming CuInSe2 (CIS) thin films was described, employing a low-cost and environmentally friendly precursor solution. The precursor solution was prepared by mixing metal acetates, ethanol, and ethanolamine. The facile formation of a precursor solution without the need to prefabricate nanoparticles enables a rapid and easy processing, and the high stability of the solution in air further ensures the precursor preparation and the film deposition in ambient conditions without a glove box. The thin film solar cell fabricated with the absorber film prepared by this route showed an initial conversion efficiency of as high as 7.72 %.


Asunto(s)
Acetatos/química , Cobre/química , Suministros de Energía Eléctrica , Etanol/química , Indio/química , Selenio/química , Energía Solar , Etanolamina/química , Soluciones , Volatilización
20.
J Biol Chem ; 285(12): 8537-42, 2010 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-20071337

RESUMEN

Plasmalogens are a major subclass of ethanolamine and choline glycerophospholipids in which a long chain fatty alcohol is attached at the sn-1 position through a vinyl ether bond. This ether-linked alkyl bond is formed in peroxisomes by replacement of a fatty acyl chain in the intermediate 1-acyl-dihydroxyacetone phosphate with a fatty alcohol in a reaction catalyzed by alkyl dihydroxyacetone phosphate synthase. Here, we demonstrate that the enzyme fatty acyl-CoA reductase 1 (Far1) supplies the fatty alcohols used in the formation of ether-linked alkyl bonds. Far1 activity is elevated in plasmalogen-deficient cells, and conversely, the levels of this enzyme are restored to normal upon plasmalogen supplementation. Down-regulation of Far1 activity in response to plasmalogens is achieved by increasing the rate of degradation of peroxisomal Far1 protein. Supplementation of normal cells with ethanolamine and 1-O-hexadecylglycerol, which are intermediates in plasmalogen biosynthesis, accelerates degradation of Far1. Taken together, our results indicate that ether lipid biosynthesis in mammalian cells is regulated by a negative feedback mechanism that senses cellular plasmalogen levels and appropriately increases or decreases Far1.


Asunto(s)
Aldehído Oxidorreductasas/metabolismo , Glicerofosfolípidos/metabolismo , Procesamiento Proteico-Postraduccional , Animales , Células CHO , Cricetinae , Cricetulus , Etanolamina/química , Éteres/química , Retroalimentación Fisiológica , Éteres de Glicerilo/química , Células HeLa , Humanos , Lípidos/química , Complejo de la Endopetidasa Proteasomal/metabolismo , ARN Interferente Pequeño/metabolismo
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