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1.
Gene ; 766: 145157, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32949697

RESUMO

Glycolytic potential (GP) calculated based on glucose, glycogen, glucose-6-phosphate, and lactate contents is a critical factor for multiple meat quality characteristics. However, the genetic basis of glycolytic metabolism is still unclear. In this study, we constructed six RNA-Seq libraries using longissimus dorsi (LD) muscles from pigs divergent for GP phenotypic values and generated the whole genome-wide gene expression profiles. Furthermore, we identified 25,880 known and 220 novel genes from these skeletal muscle libraries, and 222 differentially expressed genes (DEGs) between the higher and lower GP groups. Notably, we found that the Lactate dehydrogenase B (LDHB) and Fructose-2, 6-biphosphatase 3 (PFKFB3) expression levels were higher in the higher GP group than the lower GP group, and positively correlated with GP and lactic acid (LA), and reversely correlated with pH value at 45 min postmortem (pH45min). Besides, LDHB and PFKFB3 expression were positively correlated with drip loss measured at 48 h postmortem (DL48h) and drip loss measured at 24 h postmortem (DL24h). Collectively, we identified a serial of DEGs as the potential key candidate genes affecting GP and found that LDHB and PFKFB3 are closely related to GP and GP-related traits. Our results lay a solid basis for in-depth studies of the regulatory mechanisms on GP and GP-related traits in pigs.


Assuntos
Glicólise/genética , Músculo Esquelético/metabolismo , Suínos/genética , Transcriptoma/genética , Animais , Perfilação da Expressão Gênica/métodos , Glucose/genética , Glicogênio/genética , Isoenzimas/genética , L-Lactato Desidrogenase/genética , Ácido Láctico/metabolismo , Carne , Fenótipo , Fosfofrutoquinase-2/genética , Suínos/metabolismo
2.
Int J Food Microbiol ; 335: 108903, 2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33065381

RESUMO

Societal demand for plant-based foods is increasing. In this context, soya products fermented using lactic acid bacteria (LAB) are appealing because of their potential health and nutritional benefits. The thermophilic LAB Streptococcus thermophilus is an essential starter species in the dairy industry. However, while its physiology is well characterized, little is known about its general metabolic activity or its techno-functional properties when it is grown in soya milk. In this study, S. thermophilus LMD-9 growth, sugar production, and lactic acid production in soya milk versus cow's milk were measured. Additionally, the main metabolic pathways used by the bacterium when growing in soya milk were characterized using a proteomic approach. Streptococcus thermophilus LMD-9 growth decreased soya milk pH, from 7.5 to 4.9, in 5 h. During fermentation, acidification thus occurred in tandem with lactate production and increasing population size (final population: 1.0 × 109 CFU/ml). As growth proceeded, sucrose was consumed, and fructose was produced. The proteomic analysis (LC-MS/MS) of the strain's cytosolic and cell envelope-associated proteins revealed that proteins related to amino acid transport and nitrogen metabolism were the most common among the 328 proteins identified (63/328 = 19.2% of total proteins). The cell-wall protease PrtS was present, and an LMD-9 deletion mutant was constructed by interrupting the prtS gene (STER_RS04165 locus). Acidification levels, growth levels, and final population size were lower in the soya milk cultures when the ΔprtS strain versus the wild-type (wt) strain was used. The SDS-PAGE profile of the soluble proteins in the supernatant indicated that soya milk proteins were less hydrolyzed by the ΔprtS strain than by the wt strain. It was discovered that S. thermophilus can grow in soya milk by consuming sucrose, can hydrolyze soya proteins, and can produce acidification levels comparable to those in cow's milk. This study comprehensively examined the proteomics of S. thermophilus grown in soya milk and demonstrated that the cell-wall protease PrtS is involved in the LAB's growth in soya milk and in the proteolysis of soya proteins, which are two novel findings. These results clarify how S. thermophilus adapts to soya milk and can help inform efforts to develop new fermented plant-based foods with better-characterized biochemical and microbiological traits.


Assuntos
Proteínas de Bactérias/metabolismo , Serina Endopeptidases/metabolismo , Leite de Soja/metabolismo , Streptococcus thermophilus/crescimento & desenvolvimento , Streptococcus thermophilus/metabolismo , Animais , Fermentação , Ácido Láctico/análise , Ácido Láctico/metabolismo , Redes e Vias Metabólicas , Leite/química , Leite/metabolismo , Leite/microbiologia , Proteínas do Leite/metabolismo , Nitrogênio/metabolismo , Proteômica , Leite de Soja/química , Proteínas de Soja/metabolismo , Streptococcus thermophilus/enzimologia , Sacarose/metabolismo , Açúcares/análise , Açúcares/metabolismo
3.
Nat Commun ; 11(1): 4936, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-33024098

RESUMO

Wearable exercise trackers provide data that encode information on individual running performance. These data hold great potential for enhancing our understanding of the complex interplay between training and performance. Here we demonstrate feasibility of this idea by applying a previously validated mathematical model to real-world running activities of  ≈ 14,000 individuals with ≈ 1.6 million exercise sessions containing duration and distance, with a total distance of ≈ 20 million km. Our model depends on two performance parameters: an aerobic power index and an endurance index. Inclusion of endurance, which describes the decline in sustainable power over duration, offers novel insights into performance: a highly accurate race time prediction and the identification of key parameters such as the lactate threshold, commonly used in exercise physiology. Correlations between performance indices and training volume and intensity are quantified, pointing to an optimal training. Our findings hint at new ways to quantify and predict athletic performance under real-world conditions.


Assuntos
Modelos Teóricos , Corrida/fisiologia , Atletas , Big Data , Exercício Físico/fisiologia , Humanos , Ácido Láctico/metabolismo , Consumo de Oxigênio , Resistência Física/fisiologia , Dispositivos Eletrônicos Vestíveis
4.
PLoS One ; 15(9): e0239463, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32960920

RESUMO

This study aimed to investigate the effects of different playing strategies on external and internal loads in female tennis players during match play. Also, the underlying effects on the technical-tactical actions and activity profiles were examined. Twelve well-trained female players (age: 25±5 years; maximum oxygen uptake: 40.9±4.3 ml/kg/min) played points against an opponent of similar ability outdoors on red-clay courts. The players played points over five playing conditions. Before each condition, the players were instructed to apply either a passive, an active, or their own playing strategy (free play) to succeed. The five conditions were played in a randomized order, whereas the condition with the own strategy was always played first and served as control. During play, the external and internal loads were investigated by 10 Hz global positioning system, 100 Hz inertial measurement unit, short-range telemetry, capillary blood, and visual analog scale procedures. A 25 Hz video camera was used to examine the technical-tactical actions and activity profiles. Compared to the control condition, the passive, active, and mixed playing strategy conditions induce up to large effects on the external loads (running distances with high acceleration and deceleration), up to moderate effects on the internal loads (energy expenditures spent with high metabolic power, lactate concentration, and rating of effort), and up to very large effects on the technical-tactical actions (number of ground strokes and errors) and activity profiles (strokes per rally, rally duration, work to rest ratio, and effective playing time). Our study shows that passive, active, and mixed playing strategies have an impact on the external and internal loads, technical-tactical actions, and activity profiles of female tennis players during match play. This finding should be considered for practical purposes like match analyses and training procedures in the tennis environment.


Assuntos
Desempenho Atlético/fisiologia , Comportamento Competitivo/fisiologia , Tênis/fisiologia , Aceleração , Adulto , Feminino , Sistemas de Informação Geográfica , Humanos , Ácido Láctico/metabolismo , Oxigênio/metabolismo , Consumo de Oxigênio/fisiologia , Adulto Jovem
5.
PLoS One ; 15(9): e0239627, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32997701

RESUMO

In spite of many decades of research, the spawning migration of the European eel Anguilla anguilla from the European coast to the Sargasso Sea remains a mystery. In particular, the role of the swimbladder as a buoyancy regulating structure is not yet understood. In this study, we exercised silver eels in a swim tunnel under elevated hydrostatic pressure. The transcriptome of gas gland tissue of these exercised eels was then compared to the known transcriptome of not exercised (control) silver eel gas gland cells. Due to the high infection rate of the eel population with the swimbladder parasite Anguillicola crassus, the comparison also included an exercised group of silver eels with a heavily damaged swimbladder, and we compared the previously published transcriptome of not exercised silver eels with a highly damaged swimbladder with the exercised group of silver eels with a heavily damaged swimbladder. The comparisons of unexercised (control) silver eels with exercised silver eels with functional swimbladder (EF), as well as with exercised silver eels with damaged swimbladder (ED), both showed a significant elevation in transcripts related to glycolytic enzymes. This could also be observed within the comparison of unexercised silver eels with a highly infected swimbladder with exercised eels with a damaged swimbladder (DED). In contrast to EF, in ED a significant elevation in transcript numbers of mitochondrial NADH dehydrogenase was observed. While in EF the transcriptional changes suggested that acid production and secretion was enhanced, in ED these changes appeared to be related to thickened tissue and thus elevated diffusion distances. The remarkable number of differentially expressed transcripts coding for proteins connected to cAMP-dependent signaling pathways indicated that metabolic control in gas gland cells includes cAMP-dependent pathways. In contrast to ED, in EF significant transcriptional changes could be related to the reconstruction of the extracellular matrix, while in ED tissue repair and inflammation was more pronounced. Surprisingly, in exercised eels hypoxia inducible transcription factor expression was elevated. In EF, a large number of genes related to the circadian clock were transcriptionally modified, which may be connected to the circadian vertical migrations observed during the spawning migration.


Assuntos
Sacos Aéreos/metabolismo , Enguias/metabolismo , Glândulas Exócrinas/metabolismo , Glicólise , Pressão Hidrostática , Migração Animal , Animais , Dióxido de Carbono/metabolismo , Enguias/fisiologia , Ácido Láctico/metabolismo , Natação , Transcriptoma
6.
PLoS One ; 15(9): e0238524, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32915806

RESUMO

BACKGROUND: Markers of lung inflammation measured directly in expectorated sputum have the potential of improving the timing of antibiotic treatment in cystic fibrosis (CF). L-Lactate might be a marker of inflammation, as it is produced from glucose by polymorphonuclear neutrophils (PMNs) in CF lungs. We aimed to investigate changes in and associations between PMNs, glucose and L-lactate in sputum during antibiotic treatment. In addition, the effect of hemoglobin A1c and plasma glucose on these biomarkers were investigated. METHODS: We sampled non-induced sputum at day 0, 7, 14 and 42 in 27 chronically infected CF patients electively treated with 14 days of intravenous antibiotic. To analyze sputum samples, we used flowcytometry to count PMNs and colorimetric assays to estimate lactate and glucose. RESULTS: No changes in levels of PMNs, glucose and lactate were detected in sputum during the antibiotic treatment. Sputum PMNs were positively associated with both glucose (log coefficient = 0.20, p = 0.01) and L-lactate (log coefficient = 0.34, p<0.001). In multivariate analyses, hemoglobin A1c was negatively associated with sputum PMNs (log coefficient = -1.68, p<0.001) and plasma glucose was negatively associated with sputum glucose (log coefficient = -0.09, p = 0.02). CONCLUSIONS: In CF sputum PMNs, glucose and lactate were unchanged during elective antibiotic treatment. However, sputum PMNs were associated with both sputum glucose and sputum lactate. Surprisingly, hyperglycemia seemed to be associated with less PMNs infiltration and less glucose in CF sputum.


Assuntos
Fibrose Cística/sangue , Glucose/metabolismo , Ácido Láctico/metabolismo , Neutrófilos/metabolismo , Escarro/metabolismo , Adulto , Idoso , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Biomarcadores/metabolismo , Glicemia/metabolismo , Fibrose Cística/fisiopatologia , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Injeções Intravenosas , Contagem de Leucócitos , Masculino , Análise Multivariada , Testes de Função Respiratória , Adulto Jovem
7.
Nat Commun ; 11(1): 4236, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32843654

RESUMO

The impact of commensal bacteria on the host arises from complex microbial-diet-host interactions. Mapping metabolic interactions in gut microbial communities is therefore key to understand how the microbiome influences the host. Here we use an interdisciplinary approach including isotope-resolved metabolomics to show that in Drosophila melanogaster, Acetobacter pomorum (Ap) and Lactobacillus plantarum (Lp) a syntrophic relationship is established to overcome detrimental host diets and identify Ap as the bacterium altering the host's feeding decisions. Specifically, we show that Ap uses the lactate produced by Lp to supply amino acids that are essential to Lp, allowing it to grow in imbalanced diets. Lactate is also necessary and sufficient for Ap to alter the fly's protein appetite. Our data show that gut bacterial communities use metabolic interactions to become resilient to detrimental host diets. These interactions also ensure the constant flow of metabolites used by the microbiome to alter reproduction and host behaviour.


Assuntos
Dieta , Drosophila melanogaster/microbiologia , Drosophila melanogaster/fisiologia , Microbioma Gastrointestinal/fisiologia , Acetobacter/crescimento & desenvolvimento , Acetobacter/metabolismo , Aminoácidos/deficiência , Aminoácidos/metabolismo , Animais , Apetite , Feminino , Preferências Alimentares , Interações entre Hospedeiro e Microrganismos , Ácido Láctico/metabolismo , Lactobacillus plantarum/crescimento & desenvolvimento , Lactobacillus plantarum/metabolismo , Redes e Vias Metabólicas , Metabolômica , Consórcios Microbianos , Reprodução
8.
Int J Food Microbiol ; 333: 108796, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-32771820

RESUMO

The objective of this study was to investigate the role of yeasts in the wet fermentation of coffee beans and their contribution to coffee quality using a novel approach. Natamycin (300 ppm) was added to the fermentation mass to suppress yeast growth and their metabolic activities, and the resultant microbial ecology, bean chemistry and sensory quality were analyzed and compared to non-treated spontaneous fermentation we reported previously. The yeast community was dominated by Hanseniaspora uvarum and Pichia kudriavzevii and grew to a maximum population of about 5.5 log CFU/g in the absence of Natamycin, while when Natamycin was added yeasts were suppressed. The major bacterial species in both the spontaneous and yeast-suppressed fermentations included the lactic acid bacteria Leuconostoc mesenteroides and Lactococcus lactis, the acetic acid bacteria Gluconobacter cerinus and Acetobacter persici and the Enterobacteriaceae Enterobacter, Citrobacter and Erwinia. For both fermentations, the mucilage layers were completely degraded by the end of the process and the absence of yeast activities had no significant impact on mucilage degradation. During fermentation, reducing sugars were consumed while lactic acid was accumulated inside the beans, and its concentration was significantly higher in the spontaneous fermentation (3 times) than that where yeasts were suppressed by Natamycin. Glycerol was detected with a concentration of 0.08% in the absence of Natamycin and was not identified when Natamycin was added. Green beans fermented with yeast growth contained a higher amount of isoamyl alcohol (21 times), ethanol (3.7 times), acetaldehyde (8 times), and ethyl acetate (25 times) compared to beans fermented in the absence of yeast activities, which remained higher in the former after roasting. Beans fermented without yeast activities had a mild fruity aroma, and lower sensory scores of fragrances (7.0), flavor (6.5), acidity (6.3), body (7.0) and overall score (6.5) compared to the former. These findings demonstrated the crucial roles of yeasts in wet fermentation of coffee beans and for producing high quality coffee.


Assuntos
Bactérias/metabolismo , Café/metabolismo , Fermentação/fisiologia , Hanseniaspora/metabolismo , Pichia/metabolismo , Leveduras/metabolismo , Acetaldeído/metabolismo , Acetatos/metabolismo , Ácido Acético/metabolismo , Anti-Infecciosos/farmacologia , Bactérias/classificação , Reatores Biológicos/microbiologia , Café/microbiologia , Etanol/metabolismo , Ácido Láctico/metabolismo , Natamicina/farmacologia , Odorantes/análise , Pentanóis/metabolismo , Paladar
9.
Proc Natl Acad Sci U S A ; 117(36): 22378-22389, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32839325

RESUMO

Hyperpolarized [1-13C]pyruvate magnetic resonance spectroscopic imaging (MRSI) is a noninvasive metabolic-imaging modality that probes carbon flux in tissues and infers the state of metabolic reprograming in tumors. Prevailing models attribute elevated hyperpolarized [1-13C]pyruvate-to-[1-13C]lactate conversion rates in aggressive tumors to enhanced glycolytic flux and lactate dehydrogenase A (LDHA) activity (Warburg effect). By contrast, we find by cross-sectional analysis using genetic and pharmacological tools in mechanistic studies applied to well-defined genetically engineered cell lines and tumors that initial hyperpolarized [1-13C]pyruvate-to-[1-13C]lactate conversion rates as well as global conversion were highly dependent on and critically rate-limited by the transmembrane influx of [1-13C]pyruvate mediated predominately by monocarboxylate transporter-1 (MCT1). Specifically, in a cell-encapsulated alginate bead model, induced short hairpin (shRNA) knockdown or overexpression of MCT1 quantitatively inhibited or enhanced, respectively, unidirectional pyruvate influxes and [1-13C]pyruvate-to-[1-13C]lactate conversion rates, independent of glycolysis or LDHA activity. Similarly, in tumor models in vivo, hyperpolarized [1-13C]pyruvate-to-[1-13C]lactate conversion was highly dependent on and critically rate-limited by the induced transmembrane influx of [1-13C]pyruvate mediated by MCT1. Thus, hyperpolarized [1-13C]pyruvate MRSI measures primarily MCT1-mediated [1-13C]pyruvate transmembrane influx in vivo, not glycolytic flux or LDHA activity, driving a reinterpretation of this maturing new technology during clinical translation. Indeed, Kaplan-Meier survival analysis for patients with pancreatic, renal, lung, and cervical cancers showed that high-level expression of MCT1 correlated with poor overall survival, and only in selected tumors, coincident with LDHA expression. Thus, hyperpolarized [1-13C]pyruvate MRSI provides a noninvasive functional assessment primarily of MCT1 as a clinical biomarker in relevant patient populations.


Assuntos
Isótopos de Carbono/metabolismo , Membrana Celular/metabolismo , Ácido Láctico/metabolismo , Transportadores de Ácidos Monocarboxílicos/metabolismo , Ácido Pirúvico/metabolismo , Simportadores/metabolismo , Animais , Isótopos de Carbono/análise , Isótopos de Carbono/química , Linhagem Celular Tumoral , Membrana Celular/química , Feminino , Humanos , Ácido Láctico/análise , Ácido Láctico/química , Imagem por Ressonância Magnética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Ácido Pirúvico/análise , Ácido Pirúvico/química
10.
Science ; 369(6507)2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32855308

RESUMO

Microbial consortia are a promising alternative to monocultures of genetically modified microorganisms for complex biotransformations. We developed a versatile consortium-based strategy for the direct conversion of lignocellulose to short-chain fatty acids, which included the funneling of the lignocellulosic carbohydrates to lactate as a central intermediate in engineered food chains. A spatial niche enabled in situ cellulolytic enzyme production by an aerobic fungus next to facultative anaerobic lactic acid bacteria and the product-forming anaerobes. Clostridium tyrobutyricum, Veillonella criceti, or Megasphaera elsdenii were integrated into the lactate platform to produce 196 kilograms of butyric acid per metric ton of beechwood. The lactate platform demonstrates the benefits of mixed cultures, such as their modularity and their ability to convert complex substrates into valuable biochemicals.


Assuntos
Clostridium tyrobutyricum/metabolismo , Ácidos Graxos Voláteis/biossíntese , Lignina/metabolismo , Megasphaera elsdenii/metabolismo , Consórcios Microbianos , Veillonella/metabolismo , Biotransformação , Ácido Láctico/metabolismo
11.
PLoS One ; 15(8): e0237736, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817703

RESUMO

AIMS: To assess the impact of two different respiratory rates in hemodynamic, perfusion and ventilation parameters in a pediatric animal model of cardiac arrest (CA). METHODS: An experimental randomized controlled trial was carried out in 50 piglets under asphyxial CA. After ROSC, they were randomized into two groups: 20 and 30 respirations per minute (rpm). Hemodynamic, perfusion and ventilation parameters were measured 10 minutes after asphyxia, just before ROSC and at 5, 15, 30 and 60 minutes after ROSC. Independent medians test, Kruskal-Wallis test and χ2 test, were used to compare continuous and categorical variables, respectively. Spearman's Rho was used to assess correlation between continuous variables. A p-value <0.05 was considered significant. RESULTS: Arterial partial pressure of carbon dioxide (PaCO2) was significantly lower in the 30 rpm group after 15 minutes (41 vs. 54.5 mmHg, p <0.01), 30 minutes (39.5 vs. 51 mmHg, p < 0.01) and 60 minutes (36.5 vs. 48 mmHg, p = 0.02) of ROSC. The percentage of normoventilated subjects (PaCO2 30-50 mmHg) was significantly higher in the 30 rpm group throughout the experiment. pH normalization occurred faster in the 30 rpm group with significant differences at 60 minutes (7.40 vs. 7.34, p = 0.02). Lactic acid levels were high immediately after ROSC in both groups, but were significantly lower in the 20 rpm group at 30 (3.7 vs. 4.7 p = 0.04) and 60 minutes (2.6 vs. 3.6 p = 0.03). CONCLUSIONS: This animal model of asphyxial CA shows that a respiratory rate of 30 rpm is more effective to reach normoventilation than 20 rpm in piglets after ROSC. This ventilation strategy seems to be safe, as it does not cause hyperventilation and does not affect hemodynamics or cerebral tissue perfusion.


Assuntos
Asfixia/terapia , Parada Cardíaca/terapia , Taxa Respiratória/fisiologia , Ventilação/normas , Animais , Pressão Arterial/fisiologia , Asfixia/fisiopatologia , Dióxido de Carbono/metabolismo , Modelos Animais de Doenças , Parada Cardíaca/fisiopatologia , Humanos , Ácido Láctico/metabolismo , Pediatria , Estatísticas não Paramétricas , Suínos/fisiologia
12.
Nature ; 583(7817): 603-608, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32641832

RESUMO

Astrocytes take up glucose from the bloodstream to provide energy to the brain, thereby allowing neuronal activity and behavioural responses1-5. By contrast, astrocytes are under neuronal control through specific neurotransmitter receptors5-7. However, whether the activation of astroglial receptors can directly regulate cellular glucose metabolism to eventually modulate behavioural responses is unclear. Here we show that activation of mouse astroglial type-1 cannabinoid receptors associated with mitochondrial membranes (mtCB1) hampers the metabolism of glucose and the production of lactate in the brain, resulting in altered neuronal functions and, in turn, impaired behavioural responses in social interaction assays. Specifically, activation of astroglial mtCB1 receptors reduces the phosphorylation of the mitochondrial complex I subunit NDUFS4, which decreases the stability and activity of complex I. This leads to a reduction in the generation of reactive oxygen species by astrocytes and affects the glycolytic production of lactate through the hypoxia-inducible factor 1 pathway, eventually resulting in neuronal redox stress and impairment of behavioural responses in social interaction assays. Genetic and pharmacological correction of each of these effects abolishes the effect of cannabinoid treatment on the observed behaviour. These findings suggest that mtCB1 receptor signalling can directly regulate astroglial glucose metabolism to fine-tune neuronal activity and behaviour in mice.


Assuntos
Astrócitos/metabolismo , Metabolismo Energético , Glucose/metabolismo , Mitocôndrias/metabolismo , Receptor CB1 de Canabinoide/metabolismo , Animais , Astrócitos/citologia , Astrócitos/efeitos dos fármacos , Agonistas de Receptores de Canabinoides/farmacologia , Células Cultivadas , Dronabinol/farmacologia , Complexo I de Transporte de Elétrons/química , Complexo I de Transporte de Elétrons/metabolismo , Metabolismo Energético/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Humanos , Fator 1 Induzível por Hipóxia/metabolismo , Ácido Láctico/metabolismo , Masculino , Camundongos , Mitocôndrias/efeitos dos fármacos , Membranas Mitocondriais/metabolismo , Oxirredução , Fosforilação , Espécies Reativas de Oxigênio/metabolismo , Receptor CB1 de Canabinoide/agonistas , Comportamento Social
13.
PLoS One ; 15(7): e0235849, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32649695

RESUMO

Nephrotoxicity severely limits the chemotherapeutic efficacy of cisplatin (CDDP). Oxidative stress is associated with CDDP-induced acute kidney injury (AKI). Methylglyoxal (MG) forms advanced glycation end products that elevate oxidative stress. We aimed to explore the role of MG and its metabolite D-lactate and identify the proteins involved in CDDP-induced AKI. Six-week-old female BALB/c mice were intraperitoneally administered CDDP (5 mg/kg/day) for 3 or 5 days. Blood urea nitrogen (42.6 ± 7.4 vs. 18.3 ± 2.5; p < 0.05) and urinary N-acetyl-ß-D-glucosaminide (NAG; 4.89 ± 0.61 vs. 2.43 ± 0.31 U/L; p < 0.05) were significantly elevated in the CDDP 5-day group compared to control mice. Histological analysis confirmed AKI was successfully induced. Confocal microscopy revealed TNF-α was significantly increased in the CDDP 5-day group. Fluorogenic derivatized liquid chromatography-tandem mass spectrometry (FD-LC-MS/MS) showed the kidney MG (36.25 ± 1.68 vs. 18.95 ± 2.24 mg/g protein, p < 0.05) and D-lactate (1.78 ± 0.29 vs. 1.12 ± 0.06 mol/g protein, p < 0.05) contents were significantly higher in the CDDP 5-day group than control group. FD-LC-MS/MS proteomics identified 33 and nine altered peaks in the CDDP 3-day group and CDDP 5-day group (vs. control group); of the 35 proteins identified using the MOSCOT database, 11 were antioxidant-related. Western blotting confirmed that superoxide dismutase 1 (SOD-1) and parkinson disease protein 7 (DJ-1) are upregulated and may participate with MG in CDDP-induced AKI. This study demonstrates TNF-α, MG, SOD-1 and DJ-1 play crucial roles in CDDP-induced AKI.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Ácido Láctico/análise , Aldeído Pirúvico/análise , Lesão Renal Aguda/metabolismo , Lesão Renal Aguda/patologia , Animais , Cromatografia Líquida , Feminino , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Ácido Láctico/metabolismo , Camundongos Endogâmicos BALB C , Estresse Oxidativo/efeitos dos fármacos , Aldeído Pirúvico/metabolismo , Espectrometria de Massas em Tandem
14.
Nat Commun ; 11(1): 3547, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32669546

RESUMO

Neutrophils provide first line of host defense against bacterial infections utilizing glycolysis for their effector functions. How glycolysis and its major byproduct lactate are triggered in bone marrow (BM) neutrophils and their contribution to neutrophil mobilization in acute inflammation is not clear. Here we report that bacterial lipopolysaccharides (LPS) or Salmonella Typhimurium triggers lactate release by increasing glycolysis, NADPH-oxidase-mediated reactive oxygen species and HIF-1α levels in BM neutrophils. Increased release of BM lactate preferentially promotes neutrophil mobilization by reducing endothelial VE-Cadherin expression, increasing BM vascular permeability via endothelial lactate-receptor GPR81 signaling. GPR81-/- mice mobilize reduced levels of neutrophils in response to LPS, unless rescued by VE-Cadherin disrupting antibodies. Lactate administration also induces release of the BM neutrophil mobilizers G-CSF, CXCL1 and CXCL2, indicating that this metabolite drives neutrophil mobilization via multiple pathways. Our study reveals a metabolic crosstalk between lactate-producing neutrophils and BM endothelium, which controls neutrophil mobilization under bacterial infection.


Assuntos
Células da Medula Óssea/imunologia , Ácido Láctico/metabolismo , Neutrófilos/imunologia , Receptores Acoplados a Proteínas-G/metabolismo , Infecções por Salmonella/imunologia , Animais , Medula Óssea/irrigação sanguínea , Células da Medula Óssea/metabolismo , Modelos Animais de Doenças , Endotélio Vascular/metabolismo , Feminino , Humanos , Lipopolissacarídeos/imunologia , Masculino , Camundongos , Camundongos Knockout , Neutrófilos/metabolismo , Receptores Acoplados a Proteínas-G/genética , Infecções por Salmonella/microbiologia , Salmonella typhimurium/imunologia , Transdução de Sinais/imunologia
15.
Food Chem ; 332: 127382, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32619943

RESUMO

Sea buckthorn (Hippophaë rhamnoides L.) berries have high biological value as a rich source of phenolic compounds, fatty acids and vitamins A, C, E. Due to the high organic acid content and sour taste, the fruits are rarely used in juice production. Therefore, the study aimed to determine the metabolic activity of Lactobacillus plantarum, Lactobacillus plantarum subsp. argentoratensis and Oenococcus oeni strains along with the dynamics of changes in organic acids, sugars, phenolic compounds, and antioxidant activity during 72-h fermentation of 100% sea buckthorn and mixed with apple (1:1) juices. The strongest malolactic conversion was in mixed juices (to 75.0%). The most efficient strains were L. plantarum DSM 10492, 20174 and 6872. L. plantarum strains caused an increase in flavonols and antioxidant activity of sea buckthorn-apple juices. The results can be used to select conditions and strains in industrial-scale fermentation, to produce novel sea buckthorn products and increase their consumption.


Assuntos
Antioxidantes/química , Sucos de Frutas e Vegetais/análise , Ácido Láctico/metabolismo , Malatos/metabolismo , Fenóis/metabolismo , Açúcares/metabolismo , Fermentação , Flavonóis/química , Flavonóis/metabolismo , Frutas/química , Frutas/metabolismo , Hippophae/química , Hippophae/metabolismo , Concentração de Íons de Hidrogênio , Lactobacillus/crescimento & desenvolvimento , Lactobacillus/metabolismo , Malus/química , Malus/metabolismo , Oenococcus/crescimento & desenvolvimento , Oenococcus/metabolismo , Fenóis/química
16.
Am J Physiol Heart Circ Physiol ; 319(2): H422-H431, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32648823

RESUMO

Alterations in the metabolism of substrates such as glucose are integrally linked to the structural and functional changes that occur in the remodeling heart. Assessment of such metabolic changes under in vivo conditions would provide important insights into this interrelationship. We aimed to investigate glucose carbon metabolism in pressure-overload and volume-overload cardiac hypertrophy by using an in vivo [U-13C]glucose labeling strategy to enable analyses of the metabolic fates of glucose carbons in the mouse heart. Therefore, [U-13C]glucose was administered in anesthetized mice by tail vein infusion, and the optimal duration of infusion was established. Hearts were then excised for 13C metabolite isotopomer analysis by NMR spectroscopy. [U-13C]glucose infusions were performed in mice 2 wk following transverse aortic constriction (TAC) or aortocaval fistula (Shunt) surgery. At this time point, there were similar increases in left ventricular (LV) mass in both groups, but TAC resulted in concentric hypertrophy with impaired LV function, whereas Shunt caused eccentric hypertrophy with preserved LV function. TAC was accompanied by significant changes in glycolysis, mitochondrial oxidative metabolism, glucose metabolism to anaplerotic substrates, and de novo glutamine synthesis. In contrast to TAC, hardly any metabolic changes could be observed in the Shunt group. Taken together, in vivo [U-13C]glucose labeling is a valuable method to investigate the fate of nutrients such as glucose in the remodeling heart. We find that concentric and eccentric cardiac remodeling are accompanied by distinct differences in glucose carbon metabolism.NEW & NOTEWORTHY This study implemented a method for assessing the fate of glucose carbons in the heart in vivo and used this to demonstrate that pressure and volume overload are associated with distinct changes. In contrast to volume overload, pressure overload-induced changes affect the tricarboxylic acid cycle, glycolytic pathways, and glutamine synthesis. A better understanding of cardiac glucose metabolism under pathological conditions in vivo may provide new therapeutic strategies specific for different types of hemodynamic overload.


Assuntos
Glicemia/metabolismo , Metabolismo Energético , Hipertrofia Ventricular Esquerda/metabolismo , Miocárdio/metabolismo , Função Ventricular Esquerda , Remodelação Ventricular , Animais , Isótopos de Carbono , Ciclo do Ácido Cítrico , Modelos Animais de Doenças , Glicólise , Hipertrofia Ventricular Esquerda/fisiopatologia , Cinética , Ácido Láctico/metabolismo , Espectroscopia de Ressonância Magnética , Masculino , Camundongos Endogâmicos C57BL
17.
Int J Food Microbiol ; 333: 108792, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-32707524

RESUMO

Gamma aminobutyric acid (GABA) is a non-protein amino acid that is widely distributed in nature and its physiological importance goes beyond its role as an inhibitory neurotransmitter of the central nervous system in mammals. Since microbial fermentation is one of the most promising methods to obtain GABA, the production of this metabolite by several strains of lactic acid bacteria isolated from quinoa and amaranth sourdoughs was investigated. Lactobacillus brevis CRL 2013 produced the highest GABA levels, reaching 265 mM when optimal culture conditions were set up. The fermentative profile showed that CRL 2013 was able to catabolize carbohydrates through the phosphoketolase pathway yielding variable amounts of lactic acid, acetate and ethanol, which depended on the type of carbon source available and the presence of external electron acceptors such as fructose. Enhanced growth parameters and low GABA synthesis were associated to pentose fermentation. This impairment on GABA production machinery was partially overpassed by the addition of ethanol to the culture media. These results support the potential use of L. brevis CRL 2013 as a starter culture for the manufacture of GABA-enriched functional foods and provide further insights to the understanding of the GAD system regulation in lactic acid bacteria.


Assuntos
Pão/microbiologia , Metabolismo dos Carboidratos/fisiologia , Fermentação/fisiologia , Lactobacillus brevis/metabolismo , Ácido gama-Aminobutírico/biossíntese , Acetatos/metabolismo , Amaranthus/microbiologia , Carboidratos , Chenopodium quinoa/microbiologia , Meios de Cultura/metabolismo , Etanol/metabolismo , Ácido Láctico/metabolismo
19.
PLoS One ; 15(6): e0233264, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32479554

RESUMO

The dogs' responses to training exercise are seldom monitored using physiological variables, and cardiac autonomic regulation (CAR) is a relevant determinant of endurance-training adaptation. There are studies in the literature establishing that regular exercise could interfere with CAR in dogs, measured by heart rate and vagal-derived indexes of heart-rate-variability (HRV). However, few studies were found using a prescribed training program based on the lactate threshold (LT) to determine HRV by a 24-h Holter analysis. The purpose of this study was to test whether an endurance-training program (ETP) guided individually by LT raises time-domain measures of HRV in healthy Beagle dogs. Twenty dogs were assigned to two groups: control (C) and trained (T). The dogs from group T underwent an incremental exercise test (IET) to determine their LT. Both LT and velocity corresponding to the LT (VLT) was determined by visual inspection. T group performed an eight-week endurance-training program consisting of treadmill runs set to 70-80% of the VLT. Next, dogs from the group T have submitted to IET again. The maximal velocities (Vmax) at which achieved by the trained dogs in both IETs were determined. The group S did not undergo IETs or ETP. HRV was determined by the 24-hour-Holter at rest, before and on the 2°, 4°, 6° and 8° training weeks. To examine the HR impact on HRV, standard HRV variables were normalized to prevailing HR. VLT and Vmax rose in group T, indicating an improvement of dogs' aerobic and anaerobic capacity. The normalized standard HRV indexes were relatively attenuated since these variables had a reduction in the degree of correlation concerning an average HR. The ETP resulted in decreased resting heart rate and increased time-domain indices, highlighting the log-transformed square root of the mean sum of the squared differences between R-R intervals (Ln rMSSD). The lactate-guided endurance-training program could lead to better parasympathetic cardiac modulation in Beagle dogs.


Assuntos
Frequência Cardíaca/fisiologia , Ácido Láctico/metabolismo , Condicionamento Físico Animal/métodos , Animais , Sistema Nervoso Autônomo/fisiologia , Cães , Eletrocardiografia Ambulatorial/métodos , Eletrocardiografia Ambulatorial/veterinária , Treino Aeróbico/métodos , Teste de Esforço , Feminino , Coração/fisiologia , Masculino , Resistência Física/fisiologia , Nervo Vago/fisiologia
20.
Adv Exp Med Biol ; 1259: 113-124, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32578174

RESUMO

The tumor microenvironment consists of complex and dynamic networks of cytokines, growth factors, and metabolic products. These contribute to significant alterations in tissue architecture, cell growth, immune cell phenotype, and function. Increased glycolytic flux is commonly observed in solid tumors and is associated with significant changes in metabolites, generating high levels of lactate. While elevated glycolytic flux is a characteristic metabolic adaption of tumor cells, glycolysis is also a key metabolic program utilized by a variety of inflammatory immune cells. As such lactate and the pH changes associated with lactate transport affect not only tumor cells but also immune cells. Here we provide an overview of lactate metabolic pathways and the effects lactate has on tumor growth and immune cell function. This knowledge provides opportunities for synergistic therapeutic approaches that combine metabolic drugs, which limit tumor growth and support immune cell function, together with immunotherapies to enhance tumor eradication.


Assuntos
Ácido Láctico/metabolismo , Neoplasias/imunologia , Neoplasias/patologia , Microambiente Tumoral/imunologia , Proliferação de Células , Glicólise , Humanos
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