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1.
J Biol Chem ; 299(2): 102881, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36626986

RESUMO

Mutations in genes involved in mitochondrial proline catabolism lead to the rare genetic disorder hyperprolinemia in humans. We have previously reported that mutations of proline catabolic genes in Caenorhabditis elegans impair mitochondrial homeostasis and shorten life span, and that these effects surprisingly occur in a diet type-dependent manner. Therefore, we speculated that a specific dietary component may mitigate the adverse effects of defective proline catabolism. Here, we discovered that high dietary glucose, which is generally detrimental to health, actually improves mitochondrial homeostasis and life span in C. elegans with faulty proline catabolism. Mechanistically, defective proline catabolism results in a shift of glucose catabolism toward the pentose phosphate pathway, which is crucial for cellular redox balance. This shift helps to maintain mitochondrial reactive oxygen species homeostasis and to extend life span, as suppression of the pentose phosphate pathway enzyme GSPD-1 prevents the favorable effects of high glucose. In addition, we demonstrate that this crosstalk between proline and glucose catabolism is mediated by the transcription factor DAF-16. Altogether, these findings suggest that a glucose-rich diet may be advantageous in certain situations and might represent a potentially viable treatment strategy for disorders involving impaired proline catabolism.


Assuntos
Caenorhabditis elegans , Glucose , Longevidade , Animais , Humanos , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Glucose/metabolismo , Glucose/farmacologia , Longevidade/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Prolina/metabolismo
2.
PLoS Genet ; 17(5): e1009573, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34014977

RESUMO

Coordinated regulation of stress response pathways is crucial for cellular homeostasis. However, crosstalk between the different stress pathways and the physiological significance of this crosstalk remain poorly understood. In this study, using the model organism C. elegans, we discovered that suppression of the transcription factor LET-607/CREBH, a regulator of cellular defense and proteostatic responses, triggers adaptive induction of DAF-16-dependent stress responses. Suppression of LET-607 improves stress resistance and extends C. elegans lifespan in a DAF-16-dependent manner. We identified the sphingomyelin synthase SMS-5 to be a central mediator in the communication between LET-607 and DAF-16. SMS-5 reduces the contents of unsaturated phosphatidylcholine (PC), which activates DAF-16 through ITR-1-dependent calcium signaling and calcium-sensitive kinase PKC-2. Our data reveal the significance of crosstalk between different stress pathways in animal fitness and identify LET-607/CREBH and specific PC as regulators of DAF-16 and longevity.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Fosfatidilcolinas/metabolismo , Estresse Fisiológico , Transferases (Outros Grupos de Fosfato Substituídos)/metabolismo , Adaptação Fisiológica , Animais , Sinalização do Cálcio , Mutação em Linhagem Germinativa , Longevidade/genética , Lipídeos de Membrana/metabolismo , Proteína Quinase C/metabolismo , Transferases (Outros Grupos de Fosfato Substituídos)/genética
3.
J Biol Chem ; 298(7): 102118, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35691340

RESUMO

Sphingolipids are a class of bioactive complex lipids that have been closely associated with aging and aging-related diseases. However, the mechanism through which sphingolipids control aging has long been a mystery. Emerging studies reveal that sphingolipids exert tight control over lysosomal homeostasis and function, as evidenced by sphingolipid-related diseases, including but not limited to lysosomal storage disorders. These diseases are defined by primary lysosomal defects and a few secondary defects such as mitochondrial dysfunction. Intriguingly, recent research indicates that the majority of these defects are also associated with aging, implying that sphingolipid-related diseases and aging may share common mechanisms. We propose that the lysosome is a pivotal hub for sphingolipid-mediated aging regulation. This review discusses the critical roles of sphingolipid metabolism in regulating various lysosomal functions, with an emphasis on how such regulation may contribute to aging and aging-related diseases.


Assuntos
Envelhecimento/patologia , Lisossomos/metabolismo , Esfingolipídeos , Envelhecimento/metabolismo , Humanos , Esfingolipídeos/metabolismo
4.
Plant Cell Rep ; 42(8): 1265-1277, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37179518

RESUMO

KEY MESSAGE: A new interaction was found between PMA1 and GRF4. H2S promotes the interaction through persulfidated Cys446 of PMA1. H2S activates PMA1 to maintain K+/Na+ homeostasis through persulfidation under salt stress. Plasma membrane H+-ATPase (PMA) is a transmembrane transporter responsible for pumping protons, and its contribution to salt resistance is indispensable in plants. Hydrogen sulfide (H2S), a small signaling gas molecule, plays the important roles in facilitating adaptation of plants to salt stress. However, how H2S regulates PMA activity remains largely unclear. Here, we show a possible original mechanism for H2S to regulate PMA activity. PMA1, a predominant member in the PMA family of Arabidopsis, has a non-conservative persulfidated cysteine (Cys) residue (Cys446), which is exposed on the surface of PMA1 and located in cation transporter/ATPase domain. A new interaction of PMA1 and GENERAL REGULATORY FACTOR 4 (GRF4, belongs to the 14-3-3 protein family) was found by chemical crosslinking coupled with mass spectrometry (CXMS) in vivo. H2S-mediated persulfidation promoted the binding of PMA1 to GRF4. Further studies showed that H2S enhanced instantaneous H+ efflux and maintained K+/Na+ homeostasis under salt stress. In light of these findings, we suggest that H2S promotes the binding of PMA1 to GRF4 through persulfidation, and then activating PMA, thus improving the salt tolerance of Arabidopsis.


Assuntos
Arabidopsis , Sulfeto de Hidrogênio , Sulfeto de Hidrogênio/farmacologia , Sulfeto de Hidrogênio/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Tolerância ao Sal , Transdução de Sinais , Plantas/metabolismo , ATPases Translocadoras de Prótons/genética , ATPases Translocadoras de Prótons/metabolismo , Íons/metabolismo
5.
J Biol Chem ; 296: 100095, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33208465

RESUMO

DNA damage triggers the cellular adaptive response to arrest proliferation and repair DNA damage; when damage is too severe to be repaired, apoptosis is initiated to prevent the spread of genomic insults. However, how cells endure DNA damage to maintain cell function remains largely unexplored. By using Caenorhabditis elegans as a model, we report that DNA damage elicits cell maintenance programs, including the unfolded protein response of the endoplasmic reticulum (UPRER). Mechanistically, sublethal DNA damage unexpectedly suppresses apoptotic genes in C. elegans, which in turn increases the activity of the inositol-requiring enzyme 1/X-box binding protein 1 (IRE-1/XBP-1) branch of the UPRER by elevating unsaturated phosphatidylcholine. In addition, UPRER activation requires silencing of the lipid regulator skinhead-1 (SKN-1). DNA damage suppresses SKN-1 activity to increase unsaturated phosphatidylcholine and activate UPRER. These findings reveal the UPRER activation as an organismal adaptive response that is important to maintain cell function during DNA damage.


Assuntos
Caenorhabditis elegans/metabolismo , Dano ao DNA , Estresse do Retículo Endoplasmático , Fosfatidilcolinas/metabolismo , Animais , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Fosfatidilcolinas/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Resposta a Proteínas não Dobradas/genética
6.
PLoS Genet ; 15(4): e1008122, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31034475

RESUMO

Early exposure to some mild stresses can slow down the aging process and extend lifespan, raising the question of how early life stress might impact the somatic health of aged animals. Here, we reveal that early life heat experience triggers the establishment of epigenetic memory in soma, which promotes long-lasting stress responses and longevity in C. elegans. Unlike lethal heat shock, mild heat activates a unique transcriptional program mimicking pathogen defense responses, characterized by the enhanced expression of innate immune and detoxification genes. Surprisingly, the expression of defense response genes persists long after heat exposure, conferring enhanced stress resistance even in aged animals. Further studies identify the histone acetyltransferase CBP-1 and the chromatin remodeling SWI/SNF complex as epigenetic modulators of the long-lasting defense responses. Histone acetylation is elevated by heat stress and maintained into agedness thereafter. Accordingly, histone acetylation levels were increased on the promoters of defense genes. Moreover, disruption of epigenetic memory abrogates the longevity response to early hormetic heat stress, indicating that long-lasting defense responses are crucial for the survival of aged animals. Together, our findings provide mechanistic insights into how temperature stress experienced in early life provides animals with lifetime health benefits.


Assuntos
Resposta ao Choque Térmico , Histonas/metabolismo , Longevidade , Acetilação , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Epigênese Genética , Temperatura Alta , Imunidade Inata , Desintoxicação Metabólica Fase I , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Regiões Promotoras Genéticas
7.
J Sci Food Agric ; 98(9): 3309-3314, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29239477

RESUMO

BACKGROUND: Microbial spoilage and lipid oxidation are two major factors causing freshness deterioration of Pacific saury (Cololabis saira) during frozen storage. To provide a remedy, the effects of several natural chemicals incorporated alone or in combination in traditional water ice-glazing on the freshness and shelf-life of Pacific saury during frozen storage at -18 °C were investigated. Pacific sauries were subjected to individual quick freezing followed immediately by dipping into cold tap water (control) or solutions containing nisin, chitosan, phytic acid (single-factor experiment) or their combinations ((L9 (34 ) orthogonal experiment) for 10 s at 1 °C and then packaged in polypropylene bags before frozen storage at -18 °C. The storage duration tested was up to 12 months. RESULTS: All ice-glazing treatments with individual chemicals could significantly (P < 0.05) inhibit the accumulation of thiobarbituric acid-reactive substances (TBARS), total volatile basic nitrogen (TVB-N) and histamine as well as the increase in bacterial total viable count (TVC) compared with controls, while the combination treatments gave even better effects. The L9 (34 ) orthogonal experiment showed that the optimal combination was A2 B1 C2 (i.e. 0.5 g L-1 nisin, 5 g L-1 chitosan and 0.2 g L-1 phytic acid). The TBARS, TVB-N, histamine and TVC values in A2 B1 C2 -treated samples remained far below the maximum acceptable limit for good-freshness fish after 12 months of frozen storage at -18 °C. CONCLUSION: The incorporation of natural chemicals tested herein in ice-glazing could inhibit microbial spoilage and lipid oxidation and therefore maintain the freshness of Pacific saury during frozen storage. Under the optimal conditions, the shelf-life of Pacific saury could be extended up to 12 months at -18 °C. The study indicated that the combination treatment with natural chemicals could be commercially utilized to maintain the freshness and prolong the shelf-life of Pacific saury. © 2017 Society of Chemical Industry.


Assuntos
Quitosana , Peixes , Conservação de Alimentos/métodos , Alimentos Congelados , Nisina , Ácido Fítico , Animais , Microbiologia de Alimentos , Conservação de Alimentos/instrumentação , Histamina/análise , Gelo , Peroxidação de Lipídeos , Nitrogênio/análise , Soluções , Substâncias Reativas com Ácido Tiobarbitúrico/análise , Água
8.
J Sep Sci ; 39(22): 4384-4390, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27753266

RESUMO

In this work, a facile and environmentally friendly solid-phase microextraction assay based on on-fiber derivatization coupled with gas chromatography and mass spectrometry was developed for determining four nonvolatile index biogenic amines (putrescine, cadaverine, histamine, and tyramine) in fish samples. In the assay, the fiber was firstly dipped into a solution with isobutyl chloroformate as derivatization reagent and isooctane as extraction solvent. Thus, a thin organic liquid membrane coating was developed. Then the modified fiber was immersed into sample solution to extract four important bioamines. Afterwards, the fiber was directly inserted into gas chromatography injection port for thermal desorption. 1,7-Diaminoheptane was employed as internal standard reagent for quantification of the targets. The limits of detection of the method were 2.98-45.3 µg/kg. The proposed method was successfully applied to the detection of bioamines in several fish samples with recoveries ranging 78.9-110%. The organic reagent used for extraction was as few as microliter that can greatly reduce the harm to manipulator and environment. Moreover, the extraction procedures were very simple without concentration and elution procedures, which can greatly simplify the pretreatment process. The assay can be extended to the in situ screening of other pollutant in food safety by changing the derivatization reagent.


Assuntos
Aminas Biogênicas/análise , Peixes , Análise de Alimentos/métodos , Cromatografia Gasosa-Espectrometria de Massas , Microextração em Fase Sólida , Animais , Contaminação de Alimentos/análise , Espectrometria de Massas , Solventes
9.
Food Chem ; 439: 138083, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38043278

RESUMO

Driven by economic interests, surimi adulteration has become a high-frequency issue. This study aims to assess the feasibility of gas chromatography-ion mobility spectrometry (GC-IMS) in detecting surimi adulteration. In this work, three common adulterated surimi models were established by mixing with different fish species and ratios. The fingerprints enabled a clear discrimination among different tuna surimi, and other two surimi models with different mixing ratios also showed VOCs (volatile organic compounds) differences. Results of unsupervised principal component analysis (PCA) and supervised partial least-squares discrimination analysis (PLS-DA) revealed that different types of adulterated surimi models can be well separated from each other. A total of 12, 16, and 9 VOCs were selected as the potential markers in three simulated models by PLS-DA method, respectively. Therefore, GC-IMS coupled with certain chemometrics is expected to serve as an alternative analytical tool to directly and visually detect adulterated surimi.


Assuntos
Espectrometria de Mobilidade Iônica , Compostos Orgânicos Voláteis , Animais , Espectrometria de Mobilidade Iônica/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Compostos Orgânicos Voláteis/análise
10.
Foods ; 12(21)2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37959082

RESUMO

An intelligent indicator was developed by immobilizing bromocresol green (BCG) within the polyacrylamide (PAAm) hydrogel matrix to monitor the total volatile basic nitrogen (TVB-N) content of fish. The FTIR analysis indicated that BCG was effectively incorporated into the PAAm through the formation of intermolecular hydrogen bonds. A thermogravimetric analysis (TGA) showed that the PAAm/BCG indicator had a mere 0.0074% acrylamide monomer residue, meanwhile, the addition of BCG improved the thermal stability of the indicator. In vapor tests with various concentrations of trimethylamine, the indicator performed similarly at both 4 °C and 25 °C. The total color difference values (ΔE) exhibited a significant linear response to TVB-N levels ranging from 4.29 to 30.80 mg/100 g at 4 °C (R2 = 0.98). Therefore, the PAAm/BCG indicator demonstrated stable and sensitive color changes based on pH variations and could be employed in smart packaging for real-time assessment of fish freshness.

11.
Plant Physiol Biochem ; 196: 1-9, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36680948

RESUMO

Nitric oxide (NO), a small signaling gas molecule, participates in several growth and developmental processes in plants. However, how NO regulates cell wall biosynthesis remains unclear. Here, we demonstrate a positive effect of NO on cellulose content that may be related to S-nitrosylation of cellulose synthase 1 (CESA1) and CESA9. Two S-nitrosylated cysteine (Cys) residues, Cys562 and Cys641, which are exposed on the surface of CESA1 and CESA9 and located in the cellulose synthase catalytic domain, were identified to be S-nitrosylated. Meanwhile, Cys641 was located on the binding surface of CESA1 and CESA9, and Cys562 was very close to the binding surface. Cellulose synthase complexes (CSCs) dynamics are closely associated with cellulose content. S-nitrosylation of CESA1 and CESA9 improved particles mobility and thus increased the accumulation of cellulose in Arabidopsis hypocotyl cells. An increase in hemicellulose content as well as an alteration in pectin content facilitated cell wall extension and contributed to cell growth, finally promoting elongation of Arabidopsis hypocotyls. Overall, our work provides a path to investigate the way NO affects the cellulose content of plants.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Hipocótilo/metabolismo , Óxido Nítrico/metabolismo , Celulose/metabolismo , Mutação , Parede Celular/metabolismo
12.
J Immunol ; 185(4): 2563-9, 2010 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-20631308

RESUMO

IL-17 is a recently identified proinflammatory cytokine that plays pivotal roles in several chronic inflammatory disease models. Its expression was also found to be elevated in the serum of patients with chronic diseases. However, whether elevated systemic IL-17 expression can induce pathophysiological tissue inflammation is unknown. In this study, we demonstrated that systemic overexpression of IL-17 using an adenoviral vector could induce multiple tissue inflammation and wasting in mice. We also found that the expression of TLR4 was increased in tissues of IL-17-overexpressing mice. Moreover, TLR4 activation is required for IL-17-induced tissue inflammation and wasting, as evidenced by the absence of aggressive atrophy in gastrocnemius muscle, neutrophil accumulation, and expression of proinflammatory cytokines downstream of TLR4 in multiple tissues of TLR4-deficient mice. Further investigation revealed that TLR4 endogenous ligands high-mobility group box 1 and heat shock protein 22, were systemically upregulated and might be involved in the IL-17-induced TLR4 activation. Our results suggest that IL-17 may induce disease-associated tissue inflammation and wasting through TLR4 signaling. The study indicates a novel interaction between IL-17 and TLR4 activation and may have implications in the pathogenesis and treatment of chronic diseases.


Assuntos
Inflamação/metabolismo , Interleucina-17/metabolismo , Receptor 4 Toll-Like/metabolismo , Síndrome de Emaciação/metabolismo , Adenoviridae/genética , Animais , Western Blotting , Peso Corporal/genética , Peso Corporal/fisiologia , Quimiocinas/genética , Quimiocinas/metabolismo , Citocinas/genética , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Inflamação/sangue , Inflamação/genética , Mediadores da Inflamação/sangue , Mediadores da Inflamação/metabolismo , Interleucina-17/sangue , Interleucina-17/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Receptor 4 Toll-Like/genética , Transdução Genética , Síndrome de Emaciação/sangue , Síndrome de Emaciação/genética
13.
Front Nutr ; 9: 1066964, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36466411

RESUMO

To explore the potential application of static magnetic field (SMF) treatment in marine fish preservation, the sea bass (Lateolabrax japonicus) was exposed to SMF (5 mT) and its quality changes during cold storage were evaluated by total viable counts, water holding capacity, pH, color, and textural properties. Characteristics of the protein in the presence of SMF were investigated by measuring total sulfhydryl (SH) content, Ca2+-ATPase activity, secondary structure, and muscle microstructure. SMF treatment exhibited positive effects on fish quality, showing favorable performance on the most quality indicators, especially a significant reduction in the Microbial Counts. Furthermore, higher total SH content and Ca2+-ATPase activity were observed in SMF-treated samples, demonstrating that the oxidation and denaturation of myofibrillar protein (MP) were delayed due to SMF treatment. The transformation of α-helix to random coil was prevented in SMF-treated samples, indicating that the secondary structure of MP was stabilized by SMF treatment. The above changes in protein structures were accompanied by changes in muscle microstructure. More intact and compact structures were observed in SMF-treated samples, characterized by well-defined boundaries between myofibers. Therefore, our findings suggest that under the conditions of this article, SMF treatment could maintain the quality of fish mainly by inhibiting the growth of microorganisms and enhancing the stability of protein structures, and could be a promising auxiliary technology for preservation of aquatic products.

14.
Front Microbiol ; 13: 1030789, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36406411

RESUMO

The influence of microbiota composition and metabolisms on the safety and quality of fermented fish products is attracting increasing attention. In this study, the total viable count (TVC), pH, total volatile base nitrogen (TVB-N) as well as biogenic amines (BAs) of traditional fermented Scomber japonicus (zaoyu) were quantitatively determined. To comprehend microbial community variation and predict their functions during fermentation, 16S rRNA-based high-throughput sequencing (HTS) and phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) were employed, respectively. The fresh samples stored without fermentation were used as controls. TVC and TVB-N values increased rapidly, and the content of BAs exceeded the permissible limit on day 2 in the controls, indicating serious spoilage of the fish. In contrast, a slower increase in TVC and TVB-N was observed and the content of BAs was within the acceptable limit throughout the fermentation of zaoyu. Significant differences in microbiota composition were observed between zaoyu and the controls. The bacterial community composition of zaoyu was relatively simple and Lactobacillus was identified as the dominant microbial group. The accumulation of histamine was inhibited in zaoyu, which was positively correlated with the relative abundance of Vibrio, Enterobacter, Macrococcus, Weissella, et al. based on Redundancy analysis (RDA), while Lactobacillus showed a positive correlation with tyramine, cadaverine, and putrescine. Functional predictions, based on Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis, revealed that the relative abundance of metabolic function exhibited a decreasing trend with prolonged fermentation time and the abundance of metabolism-related genes was relatively stable in the later stage of fermentation. Those metabolisms related to the formation of BAs like histidine metabolism and arginine metabolism were inhibited in zaoyu. This study has accompanied microbiota analysis and functional metabolism with the accumulation of BAs to trace their correspondences, clarifying the roles of microorganisms in the inhibition of BAs during fermentation of Scomber japonicus.

15.
Colloids Surf B Biointerfaces ; 217: 112613, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35816883

RESUMO

To increase the solubility and targeting efficiency of curcumin (CCM) to tumors, transferrin (Tf)-CCM nanoparticles (NPs-CCM) with a CCM loading capacity of 5.2% were fabricated by Tf denaturation with hydrochloric acid, a denaturing agent, to open the hydrophobic cavity of Tf. The NPs-CCM were approximately 160 nm in size with a spherical shape. The solubility of the CCM in the nanoparticles was approximately 100,000 times greater than that of CCM alone (11 ng mL-1 vs 1.11 mg mL-1, respectively). The changes in the fluorescence spectra of Tf and 1-(anilinon)-aphthalene-8-sulfonic acid (ANS) in the NP-CCM preparation indicated that the polarity of certain hydrophobic and hydrophilic groups of Tf changed. CCM treatment of A549 cells resulted in a decrease in the mitochondrial membrane potential (MMP) and induced apoptosis through mitochondrial dependence. CCM increased the expression of phosphorylated c-Jun N-terminal kinase (JNK), P38, and extracellular signal-regulated kinase (ERK) but had a weak effect on the expression of nonphosphorylated JNK, P38, and ERK, which showed that the mitogen-activated protein kinase signaling (MAPK) transduction pathway is involved in CCM-mediated apoptosis. The half maximal inhibitory concentration (IC50) of NPs-CCM was higher than that of free CCM in A549 (16.41 ± 0.86 vs 12.51 ± 3.9 (µg mL-1), p = 0.036) and MCF-7 (9.31 ± 0.11 vs 2.44 ± 3.76 (µg mL-1), p < 0.0037) tumor cells, however the former had a greater tumor-targeting in vivo. Without the side effects of polyoxyethylene castor oil/ethanol as solvent, the hemolysis effect of NPs-CCM (0.05-1 mg mL-1) was notably lower than that of free CCM (p < 0.05). It was estimated that the half maximal lethal dose (LD50) of NPs-CCM was approximately two times that of CCM (100 mg kg-1 vs 50 mg kg-1), and the former had many advantages over that of free CCM in terms of lower toxicity and better targeting; thus, NPs-CCM can be administered at higher doses to acquire better antitumor effects than CCM alone, indicating that NPs-CCM are an effective and safe carrier for CCM delivery.


Assuntos
Curcumina , Nanopartículas , Curcumina/química , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas/química , Solubilidade , Transferrina/química
16.
Mech Ageing Dev ; 200: 111586, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34655615

RESUMO

Metabolic reprogramming is crucial for the adaptation to environmental temperature stress. It is generally accepted that fatty acid (FA) desaturation is suppressed at high temperature, which decreases the ratio of unsaturated FAs to saturated FAs (UFAs/SFAs) to maintain the fluidity of cell membranes and favor cellular survival. Here by working in C. elegans, we found that FA desaturation is essential for longevity in response to temperature upshift at the organismal level, opposite to its role in cellular survival. High temperature unexpectedly increases the contents of total fat and multiple UFA species. Specifically, monounsaturated oleic acid (OA) is required for animal survival at high temperature. Mechanistic study showed that OA acts through HSF-1, which in turn promotes histone acetylation as well as the expression of defense genes that are crucial for longevity at high temperature. Together, our findings reveal an unprecedented role for FA desaturation in organismal fitness to temperature upshift, and implicate divergent metabolic requirements between cellular and organismal survival upon temperature stress.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Sobrevivência Celular/fisiologia , Ácidos Graxos/metabolismo , Temperatura Alta , Longevidade/fisiologia , Ácido Oleico/metabolismo , Fatores de Transcrição/metabolismo , Adaptação Fisiológica , Animais , Caenorhabditis elegans , Ácidos Graxos Dessaturases/metabolismo
17.
Front Physiol ; 12: 775648, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34887779

RESUMO

Phospholipids are major membrane lipids that consist of lipid bilayers. This basic cellular structure acts as a barrier to protect the cell against various environmental insults and more importantly, enables multiple cellular processes to occur in subcellular compartments. Numerous studies have linked the complexity of membrane lipids to signal transductions, organelle functions, as well as physiological processes, and human diseases. Recently, crucial roles for membrane lipids in the aging process are beginning to emerge. In this study, we summarized current advances in our understanding of the relationship between membrane lipids and aging with an emphasis on phospholipid species. We surveyed how major phospholipid species change with age in different organisms and tissues, and some common patterns of membrane lipid change during aging were proposed. Further, the functions of different phospholipid molecules in regulating healthspan and lifespan, as well as their potential mechanisms of action, were also discussed.

18.
Nat Commun ; 12(1): 5073, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34417467

RESUMO

The contents of numerous membrane lipids change upon ageing. However, it is unknown whether and how any of these changes are causally linked to lifespan regulation. Acyl chains contribute to the functional specificity of membrane lipids. In this study, working with C. elegans, we identified an acyl chain-specific sphingolipid, C22 glucosylceramide, as a longevity metabolite. Germline deficiency, a conserved lifespan-extending paradigm, induces somatic expression of the fatty acid elongase ELO-3, and behenic acid (22:0) generated by ELO-3 is incorporated into glucosylceramide for lifespan regulation. Mechanistically, C22 glucosylceramide is required for the membrane localization of clathrin, a protein that regulates membrane budding. The reduction in C22 glucosylceramide impairs the clathrin-dependent autophagic lysosome reformation, which subsequently leads to TOR activation and longevity suppression. These findings reveal a mechanistic link between membrane lipids and ageing and suggest a model of lifespan regulation by fatty acid-mediated membrane configuration.


Assuntos
Caenorhabditis elegans/fisiologia , Ácidos Graxos não Esterificados/metabolismo , Glicoesfingolipídeos/metabolismo , Homeostase , Longevidade/fisiologia , Lisossomos/metabolismo , Animais , Proteínas de Caenorhabditis elegans/metabolismo , Ceramidas/metabolismo , Colesterol/metabolismo , Clatrina/metabolismo , Mutação em Linhagem Germinativa/genética , Proteínas de Fluorescência Verde/metabolismo , Larva/metabolismo , Modelos Biológicos , Interferência de RNA , Estresse Fisiológico
19.
G3 (Bethesda) ; 10(5): 1707-1712, 2020 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-32161088

RESUMO

The transcription factor SKN-1, the C. elegans ortholog of mammalian Nrf protein, is a well-known longevity factor, and its activation is observed in several long-lived models. SKN-1 also plays essential roles in xenobiotic and oxidative stress responses. Here, we report deleterious functions of SKN-1 in somatic stress resistance that may impair lifespan. Constitutive SKN-1 activation impairs animal resistance to several stresses, including heat, ER stress and mitochondrial stress, which result from the suppression of DAF-16, another master regulator of longevity. SKN-1 activation abrogates DAF-16 nuclear import and downregulates DAF-16 target genes under stress conditions, while SKN-1 inhibition promotes the expression of DAF-16 targets, even in long-lived mutants. Further, SKN-1 activation induces the expression of vitellogenin proteins, which are required for SKN-1-mediated suppression of DAF-16 and stress resistance. Together, these findings identify detrimental roles for SKN-1 activation in animal health, and more importantly, inspire the rethinking of the complex roles for SKN-1 in aging regulation.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Longevidade/genética , Estresse Oxidativo , Interferência de RNA , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
20.
Talanta ; 165: 326-331, 2017 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-28153261

RESUMO

Some harmful aliphatic diamines, e.g., putrescine (Put) and cadaverine (Cad), play important roles in food safety evaluation. In this study, we proposed on-fiber derivatization solid-phase microextraction analysis of non-volatile aliphatic diamines in fish using zeolitic imidazolate framework 8 (ZIF-8) as a solid-phase microextraction (SPME) coating. It was employed to encapsulate isobutyl chloroformate (IBCF, 40°C, 15min) for aqueous extraction of Put and Cad. After that, the derivatized aliphatic amines were thermally desorbed in the GC injection port and analyzed by GC-MS. The porous and hydrophobic ZIF-8 with high surface area can increase the IBCF loading amount and prevent it from decomposing, thus increasing the amine extraction effectiveness and sensitivity. In SIM mode and using the molecular ion for quantification, the limits of detection for Put and Cad were 27.1 and 33.2µgL-1, respectively under the optimal conditions. The fiber-to-fiber reproducibility values (RSDs) for three ZIF-8 coated fibers were less than 11.4% for both Put and Cad. The extraction with the new fiber was reproducible for at least 30 cycles without a noticeable decrease of performance (RSD<10%). The new fiber was successfully applied to the detection of putrescine and cadaverine in several fish samples and showed good recoveries (78.6-104%).


Assuntos
Aminas/análise , Peixes/metabolismo , Análise de Alimentos/métodos , Contaminação de Alimentos/análise , Imidazóis/química , Microextração em Fase Sólida/métodos , Aço Inoxidável/química , Zeolitas/química , Animais , Cromatografia Gasosa-Espectrometria de Massas , Polímeros/química
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