RESUMO
Sphingolipids, essential membrane components and signaling molecules in cells, have ceramides at the core of their metabolic pathways. Initially termed as "longevity assurance genes", the encoding genes of ceramide synthases are closely associated with individual aging and stress responses, although the mechanisms remain unclear. This study aims to explore the alterations and underlying mechanisms of three ceramide synthases, HYL-1, HYL-2, and LAGR-1, in the aging and stress responses of Caenorhabditis elegans. Our results showed the knockdown of HYL-1 extends the lifespan and enhance stress resistance in worms, whereas the loss of HYL-2 function significantly impairs tolerances to heat, oxidation, and ultraviolet stress. Stress intolerance induced by HYL-2 deficiency may result from intracellular mitochondrial dysfunction, accumulation of reactive oxygen species, and abnormal nuclear translocation of DAF-16 under stress conditions. Loss of HYL-2 led to a significant reduction of predominant ceramides (d17:1/C20â¼C23) as well as corresponding complex sphingolipids. Furthermore, the N-acyl chain length composition of sphingolipids underwent dramatic modifications, characterized by a decrease in C22 sphingolipids and an increase in C24 sphingolipids. Extra d18:1-ceramides resulted in diminished stress resilience in wild-type worms, while supplementation of d18:1/C16 ceramide to HYL-2-deficient worms marginally improved stress tolerance to heat and oxidation. These findings indicate the importance of appropriate ceramide content and composition in maintaining subcellular homeostasis and nuclear-cytoplasmic signal transduction during healthy aging and stress responses.
Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Esfingolipídeos , Animais , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Ceramidas/metabolismo , Fatores de Transcrição Forkhead , Longevidade , Estresse Oxidativo , Oxirredutases/metabolismo , Oxirredutases/genética , Espécies Reativas de Oxigênio/metabolismo , Esfingolipídeos/metabolismo , Estresse FisiológicoRESUMO
Acyl migration (AM) is the main side reaction in the large-scale, regio-specific lipase catalyzed production of structural triglycerides (STs). A detailed understanding of the mechanism of AM was obtained during the process of lipase-catalyzed schemes (LCSs), which play a vital role in improving the quality and total yield of STs. However, currently, the mechanism of AM remains controversial. Herein, the two mechanisms (non-catalyzed (NCM) and lipase-catalyzed (LCM)) of AM have been analyzed in detail by the density functional theory (DFT) at the molecular level. Based on the computational results, we concluded that the energy barrier of the rate-limiting step in the LCM was 18.8 kcal/mol, which is more in agreement with the available experimental value (17.8 kcal/mol), indicating that LCM could significantly accelerate the rate of AM, because it has an energy barrier ~2 times lower than that of the NCM. Interestingly, we also found that the catalytic triad (Asp-His-Ser) of the lipase and water could effectively drop the reaction barrier, which served as the general acid or base, or shuttle of the proton.
Assuntos
Teoria da Densidade Funcional , Lipase/química , Triglicerídeos/química , Catálise , Fenômenos Químicos , Esterificação , Modelos Químicos , Modelos Moleculares , Estrutura MolecularRESUMO
Cinnamomum camphora trees have a vast range of distribution in southern China and the seed oil has unique fatty acid (FA) properties and various bio-activities. In this work, Cinnamomum camphora seed oil (CCSO) was utilized to synthesize value-added cocoa butter substitute (CBS) by enzymatic interesterification. The synthesis was conducted in a solvent-free system by blending CCSO with fully hydrogenated palm oil under the catalysis of Lipozyme RM IM. The reacted products were assessed with physicochemical properties, i.e. FA composition, slip melting point (SMP), triacylglycerol (TAG), crystal polymorphism, microstructure, melting and crystallization properties and solid fat content (SFC). It showed that MCFAs (capric acid plus lauric acid) was the main fatty acid in products, accounting for over 45%. Comparing to physical blends, some novel TAG species such as LaLaLa and LaMLa/LaLaM were observed after enzymatic interesterification whereas SSS TAGs were reduced. IP presented a ball-like, well-distributed and nearly round crystal microstructure and a smaller crystal size. Moreover, it should be mentioned that SFC of IP ranging from 31.85 to 38.47% at 25 °C with most ß' crystal forms, was beneficial to improve the spreadability in term of confectionery products and baked goods. The SMP of the interesterified products was 35.75-36.15 °C which closed to the commercial CBS. Hence, the products synthesized can be used to as CBS, and the results in this study also showed CCSO have value-added applications.
RESUMO
Foliar Selenium (Se) fertilizer has been widely used to accumulate Se in rice to a level that meets the adequate intake level. The Se content in brown rice (Oryza sativa L.) was increased in a dose-dependent manner by the foliar application of sodium selenite as a fertilizer at concentrations of 25, 50, 75, and 100 g Se/ha. Selenite was mainly transformed to organic Se, that is, selenomethionine in rice. Beyond the metabolic capacity of Se in rice, inorganic Se also appeared. In addition, four extractable protein fractions in brown rice were analyzed for Se concentration. The Se concentrations in the glutelin and albumin fractions saturated with increasing Se concentration in the fertilizer compared with those in the globulin and prolamin fractions. The structural analyses by fluorescence spectroscopy, Fourier transform infrared spectrometry, and differential scanning calorimetry suggest that the secondary structure and thermostability of glutelin were altered by the Se treatments. These alterations could be due to the replacements of cysteine and methionine to selenocysteine and selenomethionine, respectively. These findings indicate that foliar fertilization of Se was effective in not only transforming inorganic Se to low-molecular-weight selenometabolites such as selenoamino acids, but also incorporating Se into general rice proteins, such as albumin, globulin glutelin, and prolamin, as selenocysteine and selenomethionine in place of cysteine and methionine, respectively.
Assuntos
Fertilizantes , Oryza/metabolismo , Proteínas de Plantas/análise , Proteínas de Plantas/metabolismo , Ácido Selenioso/análise , Ácido Selenioso/metabolismo , Selênio/análise , Selênio/metabolismo , Aminoácidos/análise , Varredura Diferencial de Calorimetria , Cromatografia Líquida , Glutens/análise , Glutens/química , Oryza/crescimento & desenvolvimento , Prolaminas/análise , Prolaminas/química , Espectrometria de Massas em TandemRESUMO
Sphingosine-1-phosphate lyase (SPL) resides at the endpoint of the sphingolipid metabolic pathway, catalyzing the irreversible breakdown of sphingosine-1-phosphate. Depletion of SPL precipitates compromised muscle morphology and function; nevertheless, the precise mechanistic underpinnings remain elusive. Here, we elucidate a model of SPL functional deficiency in Caenorhabditis elegans using spl-1 RNA interference. Within these SPL-deficient nematodes, we observed diminished motility and perturbed muscle fiber organization, correlated with the accumulation of sphingoid bases, their phosphorylated forms, and ceramides (collectively referred to as the "sphingolipid rheostat"). The disturbance in mitochondrial morphology was also notable, as SPL functional loss resulted in heightened levels of reactive oxygen species. Remarkably, the administration of the antioxidant N-acetylcysteine (NAC) ameliorates locomotor impairment and rectifies muscle fiber disarray, underscoring its therapeutic promise for ceramide-accumulation-related muscle disorders. Our findings emphasize the pivotal role of SPL in preserving muscle integrity and advocate for exploring antioxidant interventions, such as NAC supplementation, as prospective therapeutic strategies for addressing muscle function decline associated with sphingolipid/ceramide metabolism disruption.
Assuntos
Acetilcisteína , Aldeído Liases , Caenorhabditis elegans , Ceramidas , Esfingolipídeos , Animais , Caenorhabditis elegans/efeitos dos fármacos , Acetilcisteína/farmacologia , Ceramidas/metabolismo , Aldeído Liases/metabolismo , Esfingolipídeos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Músculos/efeitos dos fármacos , Músculos/metabolismo , Interferência de RNA , Esfingosina/análogos & derivados , Esfingosina/metabolismoRESUMO
Pulmonary surfactant is a lipoprotein complex lining the alveolar surface to decrease the surface tension and facilitate inspiration. Surfactant deficiency is often seen in premature infants and in children and adults with respiratory distress syndrome. Mechanical stretch of alveolar type 2 epithelial (AT2) cells during lung expansion is the primary physiological factor that stimulates surfactant secretion; however, it is unclear whether there is a mechanosensor dedicated to this process. Here, we show that loss of the mechanosensitive channels TMEM63A and TMEM63B (TMEM63A/B) resulted in atelectasis and respiratory failure in mice due to a deficit of surfactant secretion. TMEM63A/B were predominantly localized at the limiting membrane of the lamellar body (LB), a lysosome-related organelle that stores pulmonary surfactant and ATP in AT2 cells. Activation of TMEM63A/B channels during cell stretch facilitated the release of surfactant and ATP from LBs fused with the plasma membrane. The released ATP evoked Ca2+ signaling in AT2 cells and potentiated exocytic fusion of more LBs. Our study uncovered a vital physiological function of TMEM63 mechanosensitive channels in preparing the lungs for the first breath at birth and maintaining respiration throughout life.
Assuntos
Líquidos Corporais , Surfactantes Pulmonares , Adulto , Animais , Criança , Humanos , Lactente , Camundongos , Trifosfato de Adenosina , Pulmão , TensoativosRESUMO
1-Deoxysphingolipids (1-deoxySLs) are structurally distinguished from canonical sphingolipids (SLs) by absenting the essential C1-OH group that can be found in the daily diet, especially in seafoods. Excessive production of endogenous 1-deoxySLs is involved in multiple diseases. Within this review, we discuss the presence of 1-deoxySLs and their analogs from the diet and their potential physiological and pathophysiological aspects. 1-DeoxySLs as dietary and endogenously produced components are still full of mysteries and research gaps that warrant further attention.
Assuntos
Alimentos Marinhos , Esfingolipídeos , HumanosRESUMO
Lutein is a carotenoid with several beneficial functions, but its poor water solubility, chemical instability, and low bioavailability limits its application. To overcome these shortcomings, self-assembly composite nanoparticles from Stauntonia brachyanthera seed albumin (SBSA), gum Arabic (GA), and carboxymethylcellulose (CMC) were developed for lutein encapsulation. Firstly, SBSA was extracted from seeds and its physicochemical properties were evaluated. Followingly, the nanoparticles were prepared with SBSA through a heat induced self-assembly method which were modified by GA and CMC. The nanoparticles exhibited good storage, pH, and salt stability. Hydrogen bonds, hydrophobic interactions, and electrostatic interactions were proved to derive the formation of nanoparticles. The maximum effective loading capacity (LC) of the lutein in nanoparticles was 0.92 ± 0.01% with an encapsulation efficiency (EE) at 83.95 ± 0.98%. Heat stability and storage stability of lutein were significantly enhanced after encapsulation into nanoparticles. In addition, the bioaccessibility of lutein increased from 17.50 ± 2.60% to 46.80 ± 4.70% after encapsulation into nanoparticles.
Assuntos
Goma Arábica , Nanopartículas , Albuminas , Carboximetilcelulose Sódica , Luteína , Tamanho da PartículaRESUMO
The fusarium toxin 2-amino-14,16-dimethyloctadecan-3-ol (2-AOD-3-ol) is characterized as a sphingolipid analogue that can be isolated from Fusarium avenaceum-infected crops and fruits. In the current study, we discovered a group of novel metabolites of 2-AOD-3-ol from the F. avenaceum-fermented rice culture. 2-AOD-3-ol was predominantly present as a C16:1 fatty acid-assembled ceramide-mimic form rather than as a free base. Although 2-AOD-3-ol and its fatty acyl derivatives were barely detected in fresh samples, the contents of these fusarium toxins accumulated with the extension of storage time up to approximately 32-50 mg/kg dry weight in naturally stored rice, grapes, apples, and oranges. Our finding provides insight into the quality and safety of food during storage through a novel aspect: the C14-C24 fatty acyl 2-AOD-3-ol in nature, which calls for further studies to address their potential impact on human health.
Assuntos
Fusarium , Micotoxinas , Oryza , Armazenamento de Alimentos , Fusarium/metabolismo , Humanos , Micotoxinas/metabolismo , Esfingolipídeos/metabolismoRESUMO
The seed of Stauntonia brachyanthera is usually regarded as waste after fructus processing. Here, the potential utilization value of the protein isolate (SSPI) from seeds was evaluated by investigating its physicochemical and functional properties. SSPI was a complex protein containing 7 distinct subunits that had high contents of most essential amino acids. The maximum foaming capacity of SSPI was 406.7 ± 41% at pH 9.0, and the water holding/oil adsorption capacities were 4.66 g/g and 9.06 g/g, respectively. SSPI aggregates with a particle size of 154.1 ± 5.2 nm was prepared after heat treatment, which was performed as a Pickering-like stabilizer for the structuring of water-in-oil-in-water emulsions. The outer droplet size of emulsions decreased as the aggregate concentration increased. Emulsion gels could be observed with the increasing aggregate concentration and oil fraction. Further study found that the stabilities of inner water-in-oil droplets and creaming were progressively increased by increasing the aggregate concentration during storage.
Assuntos
Emulsificantes/química , Emulsificantes/isolamento & purificação , Temperatura Alta , Proteínas de Plantas/química , Proteínas de Plantas/isolamento & purificação , Ranunculales/química , Sementes/química , Adsorção , Tamanho da Partícula , Água/químicaRESUMO
The fruit of Akebia trifoliata is popular in Asia, but researches concerning the phytochemicals of A. trifoliate pericarp extract (APE) and their metabolites, bioavailability, metabolism and anti-inflammatory activity in vivo are less known. In the present study, the chemical constituents of APE and their metabolites of rats after oral administration were identified using UPLC-LTQ-Orbitrap-MS/MS. A total of 18 compounds were tentatively characterized in APE, while 8 original compounds and 8 metabolites were observed in plasma, and 10 original compounds and 39 metabolites were detected in urine. Deglycosylation, glucuronidation, methylation and sulfation were the reactions that mainly occurred in the metabolism in vivo. Meanwhile, APE supplementation decreased dextran sulphate sodium (DSS)-induced colitis in mice, ameliorating epithelial barrier disruption, suppressing the proliferation and infiltration of immune cells, modulating the secretion of nitric oxide (NO) and prostaglandin E2 (PGE2), decreasing the expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as regulating oxidative stress in vivo. The results suggested that APE triterpenoids and their metabolites as major contributors to anti-inflammatory activities, providing a scientific basis for the use of APE as a functional food to ameliorate colon health in humans.
Assuntos
Anti-Inflamatórios/farmacologia , Colite/tratamento farmacológico , Sulfato de Dextrana/efeitos adversos , Metaboloma , Extratos Vegetais/farmacologia , Ranunculales/química , Animais , Disponibilidade Biológica , Colite/induzido quimicamente , Colo/patologia , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Modelos Animais de Doenças , Frutas/química , Masculino , Camundongos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Compostos Fitoquímicos/farmacologia , Ratos , Espectrometria de Massas em TandemRESUMO
Increased processing of pulses generates large volumes of hulls, which are known as an excellent source of phenolic antioxidants. However, the bioavailability and in vivo activity of these phenolics are rarely reported. This research was therefore carried out to study the absorption, metabolism, and in vivo antioxidant activities of green pea hull (GPH) phenolics using ultrahigh-pressure liquid chromatography with a linear ion trap-high-resolution Orbitrap mass spectrometry and an oxidative stress rat model. A total of 31 phenolics, including 4 phenolic acids, 24 flavonoids, and 3 other phenolics, were tentatively identified. Ten of these phenolics and 49 metabolites were found in the plasma and urine of rats, which helped to explain the favorable changes by GPH phenolics in key antioxidant enzymes (superoxide dismutase, glutathione peroxidase, and glutathione) and indicators (total antioxidant capacity, malondialdehyde) in the plasma and different tissues of rats. This is the first comprehensive report on dry pea hull phenolics and their bioavailability, metabolic profiles, and mechanisms of in vivo antioxidant activities.