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1.
Skin Res Technol ; 30(4): e13666, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38606717

RESUMO

BACKGROUND: It is known that heparinoid, a mucopolysaccharide polysulfate, is effective in improving rough skin and promoting blood circulation as medicines for diseased areas. However, heparinoid has a molecular weight of more than 5000 and cannot penetrate healthy stratum corneum. OBJECTIVE: We tested the efficacy of sulfated oligosaccharides with a molecular weight of less than 2000 on the human skin barrier function and moisturizing function. METHODS: We measured the transepidermal water loss (TEWL) of a three-dimensional human epidermis model cultured for 3 days after topical application of sulfated oligosaccharides, then observed the effects on TEWL suppression. The mRNA levels of proteins involved in intercellular lipid transport and storage in the stratum corneum, and moisture retention were measured using RT-qPCR. RESULTS: An increase in the mRNA levels of the ATP-binding cassette subfamily A member 12 (ABCA12), which transports lipids into stratum granulosum, was confirmed. Increases were also observed in the mRNA levels of filaggrin (FLG), which is involved in the generation of natural moisturizing factors, and of caspase-14, calpain-1 and bleomycin hydrolase, which are involved in the degradation of FLG. Antibody staining confirmed that the application of sodium trehalose sulfate to 3D model skin resulted in more ABCA12, ceramide, transglutaminase1, and FLG than those in controls. In a randomized, placebo-controlled, double-blind study, participants with low stratum corneum water content applied a lotion and emulsion containing sodium trehalose sulfate to their faces for 4 weeks. Sodium trehalose sulfate decreased the TEWL and increased the stratum corneum water content. CONCLUSION: These results suggest that cosmetics containing sodium trehalose sulfate act on the epidermis by increasing barrier factors and moisturizing factors, thereby ameliorating dry skin.


Assuntos
Heparinoides , Trealose , Humanos , Trealose/farmacologia , Trealose/metabolismo , Heparinoides/metabolismo , Heparinoides/farmacologia , Pele/metabolismo , Epiderme/metabolismo , Higiene da Pele , Água/metabolismo , RNA Mensageiro/metabolismo , Sódio/metabolismo , Sódio/farmacologia
2.
ACS Infect Dis ; 10(4): 1391-1404, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38485491

RESUMO

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is the leading cause of death worldwide by infectious disease. Treatment of Mtb infection requires a six-month course of multiple antibiotics, an extremely challenging regimen necessitated by Mtb's ability to form drug-tolerant persister cells. Mtb persister formation is dependent on the trehalose catalytic shift, a stress-responsive metabolic remodeling mechanism in which the disaccharide trehalose is liberated from cell surface glycolipids and repurposed as an internal carbon source to meet energy and redox demands. Here, using a biofilm-persister model, metabolomics, and cryo-electron microscopy (EM), we found that azidodeoxy- and aminodeoxy-d-trehalose analogues block the Mtb trehalose catalytic shift through inhibition of trehalose synthase TreS (Rv0126), which catalyzes the isomerization of trehalose to maltose. Out of a focused eight-member compound panel constructed by chemoenzymatic synthesis, the natural product 2-trehalosamine exhibited the highest potency and significantly potentiated first- and second-line TB drugs in broth culture and macrophage infection assays. We also report the first structure of TreS bound to a substrate analogue inhibitor, obtained via cryo-EM, which revealed conformational changes likely essential for catalysis and inhibitor binding that can potentially be exploited for future therapeutic development. Our results demonstrate that inhibition of the trehalose catalytic shift is a viable strategy to target Mtb persisters and advance trehalose analogues as tools and potential adjunctive therapeutics for investigating and targeting mycobacterial persistence.


Assuntos
Mycobacterium tuberculosis , Tuberculose , Humanos , Mycobacterium tuberculosis/metabolismo , Trealose/química , Trealose/metabolismo , Microscopia Crioeletrônica , Tuberculose/microbiologia , Catálise
3.
J Agric Food Chem ; 72(11): 5725-5733, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38452362

RESUMO

The destructive agricultural pest oriental fruit fly, Bactrocera dorsalis (Hendel) (Diptera: Tephritidae), has been causing huge damage to the fruits and vegetable industry. Although many pertinent studies have been conducted on B. dorsalis, the functions of fat body still remain largely unknown. To this end, the comparative transcriptome analysis between fat body and carcass was performed in an attempt to provide insights into functions of fat body of B. dorsalis in the present study. A total of 1431 upregulated and 2511 downregulated unigenes were discovered in the fat body vs carcass comparison, respectively. The enrichment analysis of differentially expressed genes (DEG) revealed that most of the enriched pathways were related to metabolism. The reliability of DEG analysis was validated by qRT-PCR measurements of 12 genes in starch and sucrose metabolism pathway, including the trehalose-6-phosphate synthase (BdTPS) which was highly expressed in eggs, 5 d-old adults, and fat body. The RNAi of BdTPS significantly affected trehalose and chitin metabolism, larval growth, and larva-pupa metamorphosis. Collectively, the findings in this study enriched our understanding of fat body functions in metabolism and demonstrated the indispensable roles of BdTPS in trehalose-related physiological pathways.


Assuntos
Corpo Adiposo , Glucosiltransferases , Tephritidae , Animais , Reprodutibilidade dos Testes , Trealose/metabolismo , Perfilação da Expressão Gênica , Tephritidae/genética , Tephritidae/metabolismo , Transcriptoma
4.
PLoS One ; 19(3): e0299669, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38452127

RESUMO

To investigate the role of sugar metabolism in desiccation-sensitive seeds, we performed a natural desiccation treatment on Phoebe chekiangensis seeds in a room and systematically analyzed the changes in seed germination, sugar compounds, malondialdehyde, and relative electrical conductivity during the seed desiccation. The results revealed that the initial moisture content of P. chekiangensis seed was very high (37.06%) and the seed was sensitive to desiccation, the germination percentage of the seed decreased to 5.33% when the seed was desiccated to 22.04% of moisture content, therefore, the seeds were considered recalcitrant. Based on the logistic model, we know that the moisture content of the seeds is 29.05% when the germination percentage drops to 50% and that it is desirable to keep the seed moisture content above 31.74% during ambient transportation. During seed desiccation, sucrose and trehalose contents exhibited increasing trends, and raffinose also increased during the late stage of desiccation, however, low levels of the non-reducing sugar accumulations may not prevent the loss of seed viability caused by desiccation. Glucose and fructose predominated among sugar compounds, and they showed a slight increase followed by a significant decrease. Their depletion may have contributed to the accumulation of sucrose and raffinose family oligosaccharides. Correlation analysis revealed a significant relationship between the accumulation of sucrose, trehalose, and soluble sugars, and the reduction in seed viability. Sucrose showed a significant negative correlation with glucose and fructose. Trehalose also exhibited the same pattern of correlation. These results provided additional data and theoretical support for understanding the mechanism of sugar metabolism in seed desiccation sensitivity.


Assuntos
Dessecação , Açúcares , Açúcares/metabolismo , Dessecação/métodos , Rafinose/metabolismo , Trealose/metabolismo , Sementes/metabolismo , Germinação , Sacarose/metabolismo , Glucose/metabolismo , Frutose/metabolismo
5.
Proc Natl Acad Sci U S A ; 121(14): e2317254121, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38551840

RESUMO

Pv11 is the only animal cell line that, when preconditioned with a high concentration of trehalose, can be preserved in the dry state at room temperature for more than one year while retaining the ability to resume proliferation. This extreme desiccation tolerance is referred to as anhydrobiosis. Here, we identified a transporter that contributes to the recovery of Pv11 cells from anhydrobiosis. In general, the solute carrier 5 (SLC5)-type secondary active transporters cotransport Na+ and carbohydrates including glucose. The heterologous expression systems showed that the transporter belonging to the SLC5 family, whose expression increases upon rehydration, exhibits Na+-dependent trehalose transport activity. Therefore, we named it STRT1 (sodium-ion trehalose transporter 1). We report an SLC5 family member that transports a naturally occurring disaccharide, such as trehalose. Knockout of the Strt1 gene significantly reduced the viability of Pv11 cells upon rehydration after desiccation. During rehydration, when intracellular trehalose is no longer needed, Strt1-knockout cells released the disaccharide more slowly than the parental cell line. During rehydration, Pv11 cells became roughly spherical due to osmotic pressure changes, but then returned to their original spindle shape after about 30 min. Strt1-knockout cells, however, required about 50 min to adopt their normal morphology. STRT1 probably regulates intracellular osmolality by releasing unwanted intracellular trehalose with Na+, thereby facilitating the recovery of normal cell morphology during rehydration. STRT1 likely improves the viability of dried Pv11 cells by rapidly alleviating the significant physical stresses that arise during rehydration.


Assuntos
Chironomidae , Dessecação , Animais , Trealose/metabolismo , Larva/metabolismo , Chironomidae/genética , Insetos/metabolismo , Linhagem Celular
6.
Int J Biol Macromol ; 262(Pt 1): 129928, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38309393

RESUMO

Trehalase has attracted widespread attention in medicine, agriculture, food, and ethanol industry due to its ability to specifically degrade trehalose. Efficient expression of trehalase remains a challenge. In this study, a putative trehalase-encoding gene (Tre-zm) from Zunongwangia mangrovi was explored using gene-mining strategy and heterologously expressed in E. coli. Trehalase activity reached 3374 U·mL-1 after fermentation optimization. The scale-up fermentation in a 15 L fermenter was achieved with a trehalase production of 15,068 U·mL-1. The recombinant trehalase TreZM was purified and characterized. It displayed optimal activity at 35 °C and pH 8.5, with Mn2+, Sn2+, Na+, and Fe2+ promoting the activity. Notably, TreZM showed significant inhibition effect on biofilm forming of Staphylococcus epidermidis. The combination of TreZM with a low concentration of antibiotics could inhibit 70 % biofilm formation of Staphylococcus epidermidis and 28 % of Pseudomonas aeruginosa. Hence, this study provides a promising candidate for industrial production of trehalase and highlights its potential application to control harmful biofilms.


Assuntos
Escherichia coli , Trealase , Trealase/química , Escherichia coli/genética , Escherichia coli/metabolismo , Fermentação , Trealose/farmacologia , Trealose/metabolismo , Biofilmes
7.
Arch Microbiol ; 206(3): 105, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363385

RESUMO

Colonization of the cyanobacteria in the Bishnupur terracotta temples, one of the heritage sites of West Bengal, India is in an alarming state of deterioration now. Among the cyanobacteria Anabaena sp. (VBCCA 052002) has been isolated from most of the crust samples of terracotta monuments of Bishnupur. The identification was done using micromorphological characters and confirmed by 16S rRNA gene sequencing. The isolated strain produces enormous exopolysaccharides, which are extracted, hydrolyzed, and analyzed by HPLC. We have studied desiccation tolerance in this cyanobacterium and found biosynthesis of trehalose with an increase in durations of desiccation. The in vitro experiment shows that Chlorophyll-a and carotenoid content increase with fourteen days of desiccation, and cellular carbohydrates increase continuously. However, cellular protein decreases with desiccation. To gain insights into the survival strategies and biodeterioration mechanisms of Anabaena sp. in the desiccated conditions of the Bishnupur monuments, the present study focuses on the physiological aspects of the cyanobacteria under controlled in vitro conditions. Our study indicates that in desiccation conditions, trehalose biosynthesis takes place in Anabaena sp. As a result of the excessive sugar and polysaccharide produced, it adheres to the surface of the terracotta structure. The continuous contraction and expansion of these polysaccharides contribute to the biodeterioration of these monuments.


Assuntos
Anabaena , Dessecação , RNA Ribossômico 16S/genética , Trealose/metabolismo , Anabaena/metabolismo , Polissacarídeos/metabolismo
8.
BMC Genomics ; 25(1): 166, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347506

RESUMO

BACKGROUND: The carbon metabolism pathway is of paramount importance for the growth and development of plants, exerting a pivotal regulatory role in stress responses. The exacerbation of drought impacts on the plant carbon cycle due to global warming necessitates comprehensive investigation into the response mechanisms of Masson Pine (Pinus massoniana Lamb.), an exemplary pioneer drought-tolerant tree, thereby establishing a foundation for predicting future forest ecosystem responses to climate change. RESULTS: The seedlings of Masson Pine were utilized as experimental materials in this study, and the transcriptome, metabolome, and photosynthesis were assessed under varying temperatures and drought intensities. The findings demonstrated that the impact of high temperature and drought on the photosynthetic rate and transpiration rate of Masson Pine seedlings was more pronounced compared to individual stressors. The analysis of transcriptome data revealed that the carbon metabolic pathways of Masson Pine seedlings were significantly influenced by high temperature and drought co-stress, with a particular impact on genes involved in starch and sucrose metabolism. The metabolome analysis revealed that only trehalose and Galactose 1-phosphate were specifically associated with the starch and sucrose metabolic pathways. Furthermore, the trehalose metabolic heat map was constructed by integrating metabolome and transcriptome data, revealing a significant increase in trehalose levels across all three comparison groups. Additionally, the PmTPS1, PmTPS5, and PmTPPD genes were identified as key regulatory genes governing trehalose accumulation. CONCLUSIONS: The combined effects of high temperature and drought on photosynthetic rate, transpiration rate, transcriptome, and metabolome were more pronounced than those induced by either high temperature or drought alone. Starch and sucrose metabolism emerged as the pivotal carbon metabolic pathways in response to high temperature and drought stress in Masson pine. Trehalose along with PmTPS1, PmTPS5, and PmTPPD genes played crucial roles as metabolites and key regulators within the starch and sucrose metabolism.


Assuntos
Pinus , Pinus/genética , Pinus/metabolismo , Temperatura , Ecossistema , Secas , Carbono/metabolismo , Trealose/metabolismo , Plântula , Sacarose/metabolismo , Amido/metabolismo , Estresse Fisiológico/genética
9.
Extremophiles ; 28(1): 17, 2024 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-38342818

RESUMO

Yeasts from cold environments have a wide range of strategies to prevent the negative effects of extreme conditions, including the production of metabolites of biotechnological interest. We investigated the growth profile and production of metabolites in yeast species isolated from cold environments. Thirty-eight strains were tested for their ability to grow at different temperatures (5-30 °C) and solute concentrations (3-12.5% NaCl and 50% glucose). All strains tested were able to grow at 5 °C, and 77% were able to grow with 5% NaCl at 18 °C. We were able to group strains based on different physicochemical/lifestyle profiles such as polyextremotolerant, osmotolerant, psychrotolerant, or psychrophilic. Five strains were selected to study biomass and metabolite production (glycerol, trehalose, ergosterol, and mycosporines). These analyses revealed that the accumulation pattern of trehalose and ergosterol was related to each lifestyle profile. Also, our findings would suggest that mycosporines does not have a role as an osmolyte. Non-conventional fermentative yeasts such as Phaffia tasmanica and Saccharomyces eubayanus may be of interest for trehalose production. This work contributes to the knowledge of non-conventional yeasts with biotechnological application from cold environments, including their growth profile, metabolites, and biomass production under different conditions.


Assuntos
Basidiomycota , Trealose , Trealose/metabolismo , Cloreto de Sódio/metabolismo , Leveduras , Ergosterol/metabolismo , Temperatura Baixa
10.
Microb Cell Fact ; 23(1): 28, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38243245

RESUMO

BACKGROUND: The need to limit antibiotic therapy due to the spreading resistance of pathogenic microorganisms to these medicinal substances stimulates research on new therapeutic agents, including the treatment and prevention of animal diseases. This is one of the goals of the European Green Deal and the Farm-To-Fork strategy. Yeast biomass with an appropriate composition and exposure of cell wall polysaccharides could constitute a functional feed additive in precision animal nutrition, naturally stimulating the immune system to fight infections. RESULTS: The results of the research carried out in this study showed that the composition of Candida utilis ATCC 9950 yeast biomass differed depending on growth medium, considering especially the content of ß-(1,3/1,6)-glucan, α-glucan, and trehalose. The highest ß-(1,3/1,6)-glucan content was observed after cultivation in deproteinated potato juice water (DPJW) as a nitrogen source and glycerol as a carbon source. Isolation of the polysaccharide from yeast biomass confirmed the highest yield of ß-(1,3/1,6)-glucan after cultivation in indicated medium. The differences in the susceptibility of ß-(1,3)-glucan localized in cells to interaction with specific ß-(1,3)-glucan antibody was noted depending on the culture conditions. The polymer in cells from the DPJW supplemented with glycerol and galactose were labelled with monoclonal antibodies with highest intensity, interestingly being less susceptible to such an interaction after cell multiplication in medium with glycerol as carbon source and yeast extract plus peptone as a nitrogen source. CONCLUSIONS: Obtained results confirmed differences in the structure of the ß-(1,3/1,6)-glucan polymers considering side-chain length and branching frequency, as well as in quantity of ß-(1,3)- and ß-(1,6)-chains, however, no visible relationship was observed between the structural characteristics of the isolated polymers and its susceptibility to immunolabeling in whole cells. Presumably, other outer surface components and molecules can mask, shield, protect, or hide epitopes from antibodies. ß-(1,3)-Glucan was more intensely recognized by monoclonal antibody in cells with lower trehalose and glycogen content. This suggests the need to cultivate yeast biomass under appropriate conditions to fulfil possible therapeutic functions. However, our in vitro findings should be confirmed in further studies using tissue or animal models.


Assuntos
Candida , beta-Glucanas , Animais , Glucanos , Glicerol/metabolismo , Trealose/metabolismo , Anticorpos Monoclonais/metabolismo , Leveduras/metabolismo , Polissacarídeos/metabolismo , Parede Celular/metabolismo , beta-Glucanas/metabolismo
11.
Adv Biol (Weinh) ; 8(2): e2300404, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37968550

RESUMO

Trehalose is synthesized in insects through the trehalose 6-phosphate synthase and phosphatase (TPS/TPP) pathway. TPP dephosphorylates trehalose 6-phosphate to release trehalose. Trehalose is involved in metamorphosis, but its relation with body weight, size, and developmental timing is unexplored. The expression and activity of TPS/TPP fluctuate depending on trehalose demand. Thus, TPS/TPP inhibition can highlight the significance of trehalose in insect physiology. TPS/TPP transcript levels are elevated in the pre-pupal and pupal stages in Helicoverpa armigera. The inhibition of recombinantly expressed TPP by N-(phenylthio)phthalimide (NPP), is validated by in vitro assays. In vivo inhibition of trehalose synthesis reduces larval weight and size, hampers metamorphosis, and reduces its overall fitness. Insufficient trehalose leads to a shift in glucose flux, reduced energy, and dysregulated fatty acid oxidation. Metabolomics reaffirms the depletion of trehalose, glucose, glucose 6-phosphate, and suppressed tricarboxylic acid cycle. Reduced trehalose hampers the energy level affecting larval vitality. Through trehalose synthesis inhibition, the importance of trehalose in insect physiology and development is investigated. Also, in two other lepidopterans, TPP inhibition impedes physiology and survival. NPP is also found to be effective as an insecticidal formulation. Overall, trehalose levels affect the larval size, weight, and metabolic homeostasis for larval-pupal transition in lepidoptera.


Assuntos
Lepidópteros , Animais , Larva/metabolismo , Lepidópteros/metabolismo , Trealose/farmacologia , Trealose/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Glucose/metabolismo , Fosfatos/metabolismo
12.
Gene ; 894: 147969, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-37931857

RESUMO

Trehalose metabolism plays an important role in plant growth and response to abiotic stress. Trehalose-6-phosphate (Tre6P) can help regulate sugar homeostasis and act as an indication signal for intracellular sugar levels. Crop productivity can be greatly increased by altering the metabolic level of endogenous trehalose in plants, which can optimize the source-sink connection. In this study, the upland cotton GhTPP protein family was first homologously compared and 24 GhTPP genes were found. Transcriptome analysis revealed that GhTPP members had obvious tissue expression specificity. Among them, GhTPPA_2 (Gh_A12G223300.1) was predominantly expressed in leaves and bolls. The results of subcellular localization showed that GhTPPA_2 is localized in the chloroplast. Via PlantCare, we analyzed the promoters and found that the expression of GhTPPA_2 may be induced by light, abiotic stress, and hormones such as abscisic acid, ethylene, salicylic acid and jasmonic acid. In addition, GhTPPA_2 was overexpressed (TPPAoe) in tobacco, and we found that the TPPase activity of TPPAoe tobacco increased by 66 %. Soluble sugar content increased by 39 % and starch content increased by 27 %. Whereas, the transgenic tobacco had obvious growth advantages under 100 mM mannitol stress. Transcriptome sequencing results showed that the differential genes between TPPAoe and control were considerably enriched in functions related to photosynthesis, phosphate group metabolism, and carbohydrate metabolism. This study shows that GhTPPA_2 is involved in regulating sugar metabolism, improving soluble sugar accumulation and drought stress tolerance of tobacco, which provides theoretical basis for research on high yield and drought tolerance of crops.


Assuntos
Resistência à Seca , Açúcares , Trealose/metabolismo , Carboidratos , Fotossíntese/genética , Secas , Estresse Fisiológico/genética , Plantas Geneticamente Modificadas/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
13.
Res Microbiol ; 175(1-2): 104115, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37572823

RESUMO

Halotolerant, acidophilic, bioleaching microorganisms are crucial to biomining operations that utilize saline water. Compatible solutes play an important role in the adaptation of these microorganisms to saline environments. Acidithiobacillus ferrooxidans ATCC 23270, an iron- and sulfur-oxidizing acidophilic bacterium, synthesizes trehalose as its native compatible solute but is still sensitive to salinity. Recently, halotolerant bioleaching bacteria were found to use ectoine as their key compatible solute. Previously, bioleaching bacteria were recalcitrant to genetic manipulation; however, recent advancements in genetic tools and techniques allow successful genetic modification of A. ferrooxidans ATCC 23270. Therefore, this study aimed to test, in silico, the effect of native and synthetic compatible solute biosynthesis by A. ferrooxidans ATCC 23270 on its growth and metabolism. Metabolic network flux modelling was used to provide a computational framework for the prediction of metabolic fluxes during production of native and synthetic compatible solutes by A. ferrooxidans ATCC 23270, in silico. Complete pathways for trehalose biosynthesis by the bacterium are proposed and captured in the updated metabolic model including a newly discovered UDP-dependent trehalose synthesis pathway. Finally, the effect of nitrogen sources on compatible solute production was simulated and showed that using nitrogen gas as the sole nitrogen source enables the ectoine-producing 'engineered' microbe to oxidize up to 20% more ferrous iron in comparison to the native microbe that only produces trehalose. Therefore, the predictive outcomes of the model have the potential to guide the design and optimization of a halotolerant strain of A. ferrooxidans ATCC 23270 for saline bioleaching operations.


Assuntos
Acidithiobacillus , Trealose , Trealose/metabolismo , Acidithiobacillus/genética , Acidithiobacillus/metabolismo , Bactérias/metabolismo , Ferro/metabolismo , Nitrogênio/metabolismo
14.
Naunyn Schmiedebergs Arch Pharmacol ; 397(2): 1061-1070, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37581638

RESUMO

Aging is associated with a disturbance in the regulation of the metabolic function of the liver, which increases the risk of liver and systemic diseases. Trehalose, a natural disaccharide, has been identified to reduce dyslipidemia, hepatic steatosis, and glucose intolerance. However, the roles of trehalose on lipid metabolism in aged liver are unclear which was investigated in this study. Thirty-two male Wistar rats were randomly allocated into four groups (n = 8). Two groups of aged (24 months) and young (4 months) rats were administered 2% trehalose solution orally for 30 days. Control groups of aged and young rats did not receive any treatment. At the end of the treatment period, blood samples and liver tissues were collected. Then the expression of SIRT1, AMPK, SREBP-1c, and PPAR-α and the level of AMPK phosphorylation (p-AMPK) were quantified by real-time polymerase chain reaction and western blotting. Moreover, biochemical parameters and the histopathology of livers were evaluated. Trehalose supplementation increased the level of SIRT1, p-AMPK, and PPAR-α, whereas the level of SREBP-1c was diminished in the liver of old animals. In addition, treatment with trehalose improved histopathological features of senescent livers. Taken together, our results show that old rats developed lipogenesis in the liver which was alleviated with trehalose. Therefore, trehalose may be an effective intervention to reduce the progression of aging-induced liver diseases.


Assuntos
Proteínas Quinases Ativadas por AMP , Trealose , Masculino , Ratos , Animais , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Trealose/farmacologia , Trealose/metabolismo , PPAR alfa/genética , Sirtuína 1/genética , Sirtuína 1/metabolismo , Ratos Wistar , Fígado , Metabolismo dos Lipídeos , Lipídeos
15.
J Agric Food Chem ; 72(1): 209-218, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38128269

RESUMO

To reduce the risk of resistance development, a novel fungicide with dual specificity is demanded. Trehalose is absent in animals, and its synthases, trehalose-6-phosphate synthase (TPS) and trehalose-6-phosphate phosphatase (TPP), are safe fungicide targets. Here, we report the discovery of a dual-specificity inhibitor of MoTps1 (Magnaporthe oryzae Tps1, TPS) and MoTps2 (M. oryzae Tps2, TPP). The inhibitor, named A1-4, was obtained from a virtual screening and subsequent surface plasmon resonance screening. In in vitro assays, A1-4 interacts with MoTps1 and MoTps2-TPP (MoTps2 TPP domain) and inhibits their enzyme activities. In biological activity assays, A1-4 not only inhibits the virulence of M. oryzae on host but also causes aggregation of conidia cytosol, which is a characteristic phenotype of MoTps2. Furthermore, hydrogen/deuterium exchange mass spectrometry assays support the notion that A1-4 binds to the substrate pockets of TPS and TPP. Collectively, A1-4 is a promising hit compound for the development of safe fungicide with dual-target specificity.


Assuntos
Fungicidas Industriais , Trealose , Animais , Trealose/metabolismo , Fungicidas Industriais/farmacologia , Monoéster Fosfórico Hidrolases/genética , Monoéster Fosfórico Hidrolases/metabolismo , Metabolismo dos Carboidratos , Glucosiltransferases/química
16.
J Nanobiotechnology ; 21(1): 472, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38066538

RESUMO

Atherosclerosis, cholesterol-driven plaque formation in arteries, is a complex multicellular disease which is a leading cause of vascular diseases. During the progression of atherosclerosis, the autophagic function is impaired, resulting in lipid accumulation-mediated foam cell formation. The stimulation of autophagy is crucial for the recovery of cellular recycling process. One of the potential autophagy inducers is trehalose, a naturally occurring non-reducing disaccharide. However, trehalose has poor bioavailability due to its hydrophilic nature which results in poor penetration through cell membranes. To enhance its bioavailability, we developed trehalose-releasing nanogels (TNG) for the treatment of atherosclerosis. The nanogels were fabricated through copolymerization of 6-O-acryloyl-trehalose with the selected acrylamide-type monomers affording a high trehalose conjugation (~ 58%, w/w). TNG showed a relatively small hydrodynamic diameter (dH, 67 nm) and a uniform spherical shape and were characterized by negative ζ potential (-18 mV). Thanks to the trehalose-rich content, TNG demonstrated excellent colloidal stability in biological media containing serum and were non-hemolytic to red blood cells. In vitro study confirmed that TNG could stimulate autophagy in foam cells and enhance lipid efflux and in vivo study in ApoE-/- mice indicated a significant reduction in atherosclerotic plaques, while increasing autophagic markers. In conclusion, TNG hold great promise as a trehalose delivery system to restore impaired autophagy-mediated lipid efflux in atherosclerosis and subsequently reduce atherosclerotic plaques.


Assuntos
Aterosclerose , Placa Aterosclerótica , Animais , Camundongos , Placa Aterosclerótica/tratamento farmacológico , Trealose/farmacologia , Trealose/metabolismo , Nanogéis , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Autofagia , Lipídeos
17.
BMC Plant Biol ; 23(1): 641, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38082382

RESUMO

BACKGROUND: Trehalose-6-phosphate phosphatase (TPP) is an essential enzyme catalyzing trehalose synthesis, an important regulatory factor for plant development and stress response in higher plants. However, the TPP gene family in soybean has not been reported. RESULTS: A comprehensive analysis of the TPP gene family identified 18 GmTPPs classified into eight groups based on the phylogenetic relationships and the conservation of protein in six monocot and eudicot plants. The closely linked subfamilies had similar motifs and intron/exon numbers. Segmental duplication was the main driving force of soybean GmTPPs expansion. In addition, analysis of the cis-regulatory elements and promoter regions of GmTPPs revealed that GmTPPs regulated the response to several abiotic stresses. Moreover, RNA-seq and qRT-PCR analysis of the tissue-specific GmTPPs under different abiotic stresses revealed that most GmTPPs were associated with response to different stresses, including cold, drought, saline-alkali, and exogenous trehalose. Notably, exogenous trehalose treatment up-regulated the expression of most TPP genes under saline-alkali conditions while increasing the carbohydrate and trehalose levels and reducing reactive oxygen species (ROS) accumulation in soybean sprouts, especially in the saline-alkali tolerant genotype. Furthermore, the interaction network and miRNA target prediction revealed that GmTPPs interacted with abiotic stress response-related transcription factors. CONCLUSIONS: The findings in this study lay a foundation for further functional studies on TPP-based breeding to improve soybean development and stress tolerance.


Assuntos
Trealose , Trealose/metabolismo , Transcriptoma , Filogenia , Melhoramento Vegetal , Estresse Fisiológico/genética , Álcalis , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
18.
Physiol Plant ; 175(6): e14096, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38148193

RESUMO

Trehalose 6-phosphate (Tre6P), the intermediate of trehalose biosynthesis, is an essential signalling metabolite linking plant growth and development to carbon metabolism. While recent work has focused predominantly on the enzymes that produce Tre6P, little is known about the proteins that catalyse its degradation, the trehalose 6-phosphate phosphatases (TPPs). Often occurring in large protein families, TPPs exhibit cell-, tissue- and developmental stage-specific expression patterns, suggesting important regulatory functions in controlling local levels of Tre6P and trehalose as well as Tre6P signalling. Furthermore, growing evidence through gene expression studies and transgenic approaches shows that TPPs play an important role in integrating environmental signals with plant metabolism. This review highlights the large diversity of TPP isoforms in model and crop plants and identifies how modulating Tre6P metabolism in certain cell types, tissues, and at different developmental stages may promote stress tolerance, resilience and increased crop yield.


Assuntos
Arabidopsis , Fosfatos Açúcares , Arabidopsis/metabolismo , Trealose/metabolismo , Plantas/genética , Plantas/metabolismo , Fosfatos Açúcares/metabolismo , Monoéster Fosfórico Hidrolases/genética , Monoéster Fosfórico Hidrolases/metabolismo , Fosfatos
19.
J Bacteriol ; 205(11): e0029223, 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37916804

RESUMO

IMPORTANCE: Survival during starvation hinges on the ability to manage intracellular energy reserves and to initiate appropriate metabolic responses to perturbations of such reserves. How Escherichia coli manage carbon storage systems under starvation stress, as well as transpose changes in intracellular metabolite levels into regulatory signals, is not well understood. Endogenous trehalose metabolism may be at the center of these processes, coupling carbon storage with carbon starvation responses. The coupled transport to the periplasm and subsequent hydrolysis of trehalose back to glucose for transport to the cytoplasm may function as a crucial metabolic signaling pathway. Although trehalose has been characterized as a stress protectant in E. coli, the disaccharide also functions as both an energy storage compound and a regulator of carbohydrate metabolism in fungi, plants, and other bacteria. Our research explores the metabolic regulatory properties of trehalose in E. coli and a potential mechanism by which the intracellular carbon pool is interconnected with regulatory circuits, enabling long-term survival.


Assuntos
Escherichia coli , Trealose , Escherichia coli/genética , Escherichia coli/metabolismo , Trealose/metabolismo , Periplasma/metabolismo , Transdução de Sinais , Carbono/metabolismo
20.
Sci Rep ; 13(1): 19973, 2023 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-37968317

RESUMO

Cassava storage roots (SR) are an important source of food energy and raw material for a wide range of applications. Understanding SR initiation and the associated regulation is critical to boosting tuber yield in cassava. Decades of transcriptome studies have identified key regulators relevant to SR formation, transcriptional regulation and sugar metabolism. However, there remain uncertainties over the roles of the regulators in modulating the onset of SR development owing to the limitation of the widely applied differential gene expression analysis. Here, we aimed to investigate the regulation underlying the transition from fibrous (FR) to SR based on Dynamic Network Biomarker (DNB) analysis. Gene expression analysis during cassava root initiation showed the transition period to SR happened in FR during 8 weeks after planting (FR8). Ninety-nine DNB genes associated with SR initiation and development were identified. Interestingly, the role of trehalose metabolism, especially trehalase1 (TRE1), in modulating metabolites abundance and coordinating regulatory signaling and carbon substrate availability via the connection of transcriptional regulation and sugar metabolism was highlighted. The results agree with the associated DNB characters of TRE1 reported in other transcriptome studies of cassava SR initiation and Attre1 loss of function in literature. The findings help fill the knowledge gap regarding the regulation underlying cassava SR initiation.


Assuntos
Manihot , Manihot/metabolismo , Trealose/metabolismo , Raízes de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Perfilação da Expressão Gênica
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