-
International Journal of Molecular... Apr 2024Numerous post-translational modifications are involved in oocyte maturation and embryo development. Recently, lactylation has emerged as a novel epigenetic modification...
Numerous post-translational modifications are involved in oocyte maturation and embryo development. Recently, lactylation has emerged as a novel epigenetic modification implicated in the regulation of diverse cellular processes. However, it remains unclear whether lactylation occurs during oocyte maturation and embryo development processes. Herein, the lysine lactylation (Kla) modifications were determined during mouse oocyte maturation and early embryo development by immunofluorescence staining. Exogenous lactate was supplemented to explore the consequences of modulating histone lactylation levels on oocyte maturation and embryo development processes by transcriptomics. Results demonstrated that lactylated proteins are widely present in mice with tissue- and cell-specific distribution. During mouse oocyte maturation, immunofluorescence for H3K9la, H3K14la, H4K8la, and H4K12la was most intense at the germinal vesicle (GV) stage and subsequently weakened or disappeared. Further, supplementing the culture medium with 10 mM sodium lactate elevated both the oocyte maturation rate and the histone Kla levels in GV oocytes, and there were substantial increases in Kla levels in metaphase II (MII) oocytes. It altered the transcription of molecules involved in oxidative phosphorylation. Moreover, histone lactylation levels changed dynamically during mouse early embryogenesis. Sodium lactate at 10 mM enhanced early embryo development and significantly increased lactylation, while impacting glycolytic gene transcription. This study reveals the roles of lactylation during oocyte maturation and embryo development, providing new insights to improving oocyte maturation and embryo quality.
Topics: Animals; Histones; Oocytes; Mice; Embryonic Development; Female; Protein Processing, Post-Translational; Oogenesis; Lysine; In Vitro Oocyte Maturation Techniques; Gene Expression Regulation, Developmental
PubMed: 38732042
DOI: 10.3390/ijms25094821 -
Physiology & Behavior Dec 2012Panic disorder (PD) is a severe anxiety disorder characterized by susceptibility to induction of panic attacks by subthreshold interoceptive stimuli such as sodium... (Review)
Review
Panic disorder (PD) is a severe anxiety disorder characterized by susceptibility to induction of panic attacks by subthreshold interoceptive stimuli such as sodium lactate infusions or hypercapnia induction. Here we review a model of panic vulnerability in rats involving chronic inhibition of GABAergic tone in the dorsomedial/perifornical hypothalamic (DMH/PeF) region that produces enhanced anxiety and freezing responses in fearful situations, as well as a vulnerability to displaying acute panic-like increases in cardioexcitation, respiration activity and "flight" associated behavior following subthreshold interoceptive stimuli that do not elicit panic responses in control rats. This model of panic vulnerability was developed over 15 years ago and has provided an excellent preclinical model with robust face, predictive and construct validity. The model recapitulates many of the phenotypic features of panic attacks associated with human panic disorder (face validity) including greater sensitivity to panicogenic stimuli demonstrated by sudden onset of anxiety and autonomic activation following an administration of a sub-threshold (i.e., do not usually induce panic in healthy subjects) stimulus such as sodium lactate, CO(2), or yohimbine. The construct validity is supported by several key findings; DMH/PeF neurons regulate behavioral and autonomic components of a normal adaptive panic response, as well as being implicated in eliciting panic-like responses in humans. Additionally, patients with PD have deficits in central GABA activity and pharmacological restoration of central GABA activity prevents panic attacks, consistent with this model. The model's predictive validity is demonstrated by not only showing panic responses to several panic-inducing agents that elicit panic in patients with PD, but also by the positive therapeutic responses to clinically used agents such as alprazolam and antidepressants that attenuate panic attacks in patients. More importantly, this model has been utilized to discover novel drugs such as group II metabotropic glutamate agonists and a new class of translocator protein enhancers of GABA, both of which subsequently showed anti-panic properties in clinical trials. All of these data suggest that this preparation provides a strong preclinical model of some forms of human panic disorders.
Topics: Animals; Disease Models, Animal; GABAergic Neurons; Hypothalamus; Panic; Panic Disorder; Rats
PubMed: 22484112
DOI: 10.1016/j.physbeh.2012.03.016 -
Frontiers in Oncology 2022Telomerase activity is elevated in most cancer cells and is required for telomere length maintenance and immortalization of cancer cells. Glucose metabolic reprogramming...
Telomerase activity is elevated in most cancer cells and is required for telomere length maintenance and immortalization of cancer cells. Glucose metabolic reprogramming is a hallmark of cancer and accompanied with increased expression of key metabolic enzymes. Whether these enzymes influence telomerase activity and cell immortalization remains unclear. In the current study, we screened metabolic enzymes using telomerase activity assay and identified lactate dehydrogenase B (LDHB) as a regulator of telomerase activity. Sodium lactate and sodium pyruvate did not influence telomerase activity, indicating LDHB regulates telomerase activity independent of its metabolism regulating function. Further studies revealed that LDHB directly interacted with TERT and regulated the interaction between TERT and TERC. Additionally, long-term knockdown of LDHB inhibited cancer cell growth and induced cell senescence and . Higher LDHB expression was detected in pancreatic cancer tissues compared with that in adjacent normal tissues and expression of LDHB correlated negatively with prognosis. Thus, we identified LDHB as the first glucose metabolic enzyme contributing to telomerase activity and pancreatic cancer cell immortalization.
PubMed: 35669414
DOI: 10.3389/fonc.2022.821620 -
FEBS Open Bio Oct 2021Lactate is considered to be a signaling molecule that induces mitochondrial adaptation and muscle hypertrophy. The purpose of this study was to examine whether lactate...
Lactate is considered to be a signaling molecule that induces mitochondrial adaptation and muscle hypertrophy. The purpose of this study was to examine whether lactate administration attenuates denervation-induced loss of mitochondrial content and muscle mass. Eight-week-old male Institute of Cancer Research mice underwent unilateral sciatic nerve transection surgery. The contralateral hindlimb served as a sham-operated control. From the day of surgery, mice were injected intraperitoneally with PBS or sodium lactate (equivalent to 1 g·kg body weight) once daily for 9 days. After 10 days of denervation, gastrocnemius muscle weight decreased to a similar extent in both the PBS- and lactate-injected groups. Denervation significantly decreased mitochondrial enzyme activity, protein content, and MCT4 protein content in the gastrocnemius muscle. However, lactate administration did not have any significant effects. The current observations suggest that daily lactate administration for 9 days does not affect denervation-induced loss of mitochondrial content and muscle mass.
Topics: Animals; Lactic Acid; Male; Mice; Mitochondria; Muscle Denervation; Muscle, Skeletal; Sciatic Nerve
PubMed: 34510821
DOI: 10.1002/2211-5463.13293 -
The Effects of Exogenous Lactate Administration on the IGF1/Akt/mTOR Pathway in Rat Skeletal Muscle.International Journal of Environmental... Oct 2020We investigated the effects of oral lactate administration on protein synthesis and degradation factors in rats over 2 h after intake. Seven-week-old male Sprague-Dawley...
We investigated the effects of oral lactate administration on protein synthesis and degradation factors in rats over 2 h after intake. Seven-week-old male Sprague-Dawley rats were randomly divided into four groups ( = 8/group); their blood plasma levels of lactate, glucose, insulin, and insulin-like growth factor 1 (IGF1) were examined following sacrifice at 0, 30, 60, or 120 min after sodium lactate (2 g/kg) administration. We measured the mRNA expression levels of protein synthesis-related genes (IGF receptor, protein kinase B (Akt), mammalian target of rapamycin (mTOR)) or degradation-related genes (muscle RING-finger protein-1 (MuRF1), atrogin-1) and analyzed the protein expression and phosphorylation (activation) of Akt and mTOR. Post-administration, the plasma lactate concentration increased to 3.2 mmol/L after 60 min. Plasma glucose remained unchanged throughout, while insulin and IGF1 levels decreased after 30 min. The mRNA levels of IGF receptor and mTOR peaked after 60 min, and Akt expression was significantly upregulated from 30 to 120 min. However, MuRF1 and atrogin-1 expression levels were unaffected. Akt protein phosphorylation did not change significantly, whereas mTOR phosphorylation significantly increased after 30 min. Thus, lactate administration increased the mRNA and protein expression of protein-synthesis factors, suggesting that it can potentially promote skeletal muscle synthesis.
Topics: Animals; Insulin-Like Growth Factor I; Lactic Acid; Male; Muscle, Skeletal; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Signal Transduction; TOR Serine-Threonine Kinases
PubMed: 33113811
DOI: 10.3390/ijerph17217805 -
Channels (Austin, Tex.) 2015Recently, we established that recurrent activity evokes network sodium oscillations in neurons and astrocytes in hippocampal tissue slices. Interestingly, metabolic...
Recently, we established that recurrent activity evokes network sodium oscillations in neurons and astrocytes in hippocampal tissue slices. Interestingly, metabolic integrity of astrocytes was essential for the neurons' capacity to maintain low sodium and to recover from sodium loads, indicating an intimate metabolic coupling between the 2 cell types. Here, we studied if lactate can support neuronal sodium homeostasis during impaired energy metabolism by analyzing whether glucose removal, pharmacological inhibition of glycolysis and/or addition of lactate affect cellular sodium regulation. Furthermore, we studied the effect of lactate on sodium regulation during recurrent network activity and upon inhibition of the glial Krebs cycle by sodium-fluoroacetate. Our results indicate that lactate is preferentially used by neurons. They demonstrate that lactate supports neuronal sodium homeostasis and rescues the effects of glial poisoning by sodium-fluoroacetate. Altogether, they are in line with the proposed transfer of lactate from astrocytes to neurons, the so-called astrocyte-neuron-lactate shuttle.
Topics: Animals; Astrocytes; Energy Metabolism; Female; Glucose; Glutamic Acid; Hippocampus; Homeostasis; Lactates; Male; Mice, Inbred BALB C; Neuroglia; Neurons; Signal Transduction; Sodium
PubMed: 26039160
DOI: 10.1080/19336950.2015.1050163 -
Journal of Food Protection Jun 2024The effect of fermentation and drying temperatures, caliber, and sodium lactate on Listeria monocytogenes inactivation was studied in salami, produced in a pilot scale,...
Effects of Fermentation Temperature, Drying Temperature, Caliber Size, Starter Culture, and Sodium Lactate on Listeria monocytogenes Inactivation During Salami Production.
The effect of fermentation and drying temperatures, caliber, and sodium lactate on Listeria monocytogenes inactivation was studied in salami, produced in a pilot scale, inoculated with 10 CFU/g of Listeria innocua ATCC® 33090 as a surrogate microorganism for L. monocytogenes. Fermentation temperature varied between 24 and 30°C, drying temperature between 14 and 20°C, caliber between 5.1 and 13.2 cm, and sodium lactate initial concentrations in salamis were 0 and 2%. L. innocua counts, pH and water activity were determined in salamis over time. Sodium lactate (2%) decreased pH drop and Listeria inactivation during fermentation. Baranyi & Roberts equation was used to fit the experimental data and to estimate, for each test condition, inactivation rate (k), initial (Y), and final counts of L. innocua (Y). Total inactivation was calculated as Y minus Y (Y-Y). Then, using a Box Benkhen experimental design, a quadratic model for k and a two-factor interaction model (2FI) for Y - Y were obtained as functions of fermentation temperature, drying temperature, and caliber size. The models predicted that maximum k and Y -Y, -2.62 ± 0.14 log CFU/g/day and 4.5 ± 0.1 log CFU/g, respectively, would be obtained fermenting at 30°C and drying at 20°C regardless of caliber. Drying at 14°C allowed Listeria growth until a water activity (a) of 0.92 was reached. Therefore, if initial Listeria contamination is high (3 log CFU/g), drying at low temperatures will compromise product safety.
Topics: Listeria monocytogenes; Fermentation; Temperature; Food Microbiology; Sodium Lactate; Colony Count, Microbial; Meat Products; Listeria; Hydrogen-Ion Concentration; Food Preservation; Food Handling
PubMed: 38697485
DOI: 10.1016/j.jfp.2024.100286 -
Frontiers in Nutrition 2022Previous studies have reported that sodium bicarbonate ingestion may enhance high-intensity exercise performance and cause severe gastrointestinal distress. However,...
BACKGROUND
Previous studies have reported that sodium bicarbonate ingestion may enhance high-intensity exercise performance and cause severe gastrointestinal distress. However, enteric-coated sodium bicarbonate may reduce gastrointestinal symptoms of sodium bicarbonate after oral administration. This remains to be confirmed. This study aimed to verify the effects of serial and acute enteric-coated sodium bicarbonate supplementation on anaerobic performance, physiological profile, and metabolomics in healthy young men.
METHODS
Healthy young males ( = 12) ingested 0.2 g/kg body mass of enteric-coated sodium bicarbonate (ES) in serial enteric-coated sodium bicarbonate (SES, continuous ES supplementation for 5 days) and acute enteric-coated sodium bicarbonate (AES, acute ES supplementation before exercise) or a placebo (PL) in a randomized crossover design. After each supplement protocol, the participants completed four Wingate anaerobic tests (WAT). The first three Wingate tests (testing anaerobic capacity) were performed with a 5-min passive recovery between each. After the third Wingate test, participants were required to complete a 50-min recovery followed by a fourth WAT test (testing the recovery of anaerobic capacity after 50-min intervals). Blood lactate (BLA), heart rate (HR), and ratings of perceived exertion (RPE) were measured in all conditions during the test, as was the subjective gastrointestinal-symptoms assessment questionnaire (GSAQ). Mean power (MP) and peak power (PP) were recorded after four WATs. Urine samples were collected before the test and 50 min after the 3rd WAT.
RESULTS
Serial enteric-coated sodium bicarbonate supplementation improved anaerobic capacity in the third bout of WATs, as observed based on an increase in mean power (SES vs. PL (613 ± 57 vs. 542 ± 64 W), = 0.024) and peak power (SES vs. PL (1,071 ± 149 vs. 905 ± 150 W), = 0.016). Acute ES supplementation did not affect anaerobic capacity. The occurrence of gastrointestinal symptoms after enteric-coated sodium bicarbonate supplementation was minimal and no difference compared to placebo in the current study. In particular, serial enteric-coated sodium bicarbonate supplementation had no gastrointestinal side effects before the test. The AES and SES groups had a trivial effect on blood lactate compared to the PLA group. There was no significant difference in HR and RPE among the three groups. Based on targeted metabolomics analysis, the 50 min after the third WAT, the levels of lactate ( < 0.001), L-Malic acid ( < 0.05), and oxaloacetate ( < 0.05) were significantly higher in the SES group than in the PL group. Compared with the AES group, the levels of lactate and fumarate in the SES group were significantly increased ( < 0.05).
CONCLUSIONS
Our study indicates that serial enteric-coated sodium bicarbonate supplementation positively improves anaerobic performance among healthy young men. However, acute ingestion of enteric-coated sodium bicarbonate did not improve anaerobic exercise performance. Either with serial or acute supplementation doses, enteric-coated sodium bicarbonate produced fewer gastrointestinal symptoms and no difference compared to placebo, especially with no gastrointestinal side effects after serial supplementation. Serial and acute supplementation of enteric-coated sodium bicarbonate might tend to promote lactate clearance. Furthermore, serial enteric-coated sodium bicarbonate ingestion may cause changes in the metabolism of lactate, L-Malic acid, oxaloacetate, and fumarate 50 min after exercise, which presumably may promote the tricarboxylic acid cycle and lactate clearance.
PubMed: 36051902
DOI: 10.3389/fnut.2022.931671 -
PLoS Biology Jul 2015Lactate has long been considered a "waste" by-product of cell metabolism, and it accumulates at sites of inflammation. Recent findings have identified lactate as an...
Lactate has long been considered a "waste" by-product of cell metabolism, and it accumulates at sites of inflammation. Recent findings have identified lactate as an active metabolite in cell signalling, although its effects on immune cells during inflammation are largely unexplored. Here we ask whether lactate is responsible for T cells remaining entrapped in inflammatory sites, where they perpetuate the chronic inflammatory process. We show that lactate accumulates in the synovia of rheumatoid arthritis patients. Extracellular sodium lactate and lactic acid inhibit the motility of CD4+ and CD8+ T cells, respectively. This selective control of T cell motility is mediated via subtype-specific transporters (Slc5a12 and Slc16a1) that we find selectively expressed by CD4+ and CD8+ subsets, respectively. We further show both in vitro and in vivo that the sodium lactate-mediated inhibition of CD4+ T cell motility is due to an interference with glycolysis activated upon engagement of the chemokine receptor CXCR3 with the chemokine CXCL10. In contrast, we find the lactic acid effect on CD8+ T cell motility to be independent of glycolysis control. In CD4+ T helper cells, sodium lactate also induces a switch towards the Th17 subset that produces large amounts of the proinflammatory cytokine IL-17, whereas in CD8+ T cells, lactic acid causes the loss of their cytolytic function. We further show that the expression of lactate transporters correlates with the clinical T cell score in the synovia of rheumatoid arthritis patients. Finally, pharmacological or antibody-mediated blockade of subtype-specific lactate transporters on T cells results in their release from the inflammatory site in an in vivo model of peritonitis. By establishing a novel role of lactate in control of proinflammatory T cell motility and effector functions, our findings provide a potential molecular mechanism for T cell entrapment and functional changes in inflammatory sites that drive chronic inflammation and offer targeted therapeutic interventions for the treatment of chronic inflammatory disorders.
Topics: Animals; Arthritis, Rheumatoid; CD4-Positive T-Lymphocytes; Cell Movement; Chemokines; Female; Glycolysis; Humans; Inflammation; Lactic Acid; Mice, Inbred C57BL; Synovial Fluid
PubMed: 26181372
DOI: 10.1371/journal.pbio.1002202 -
Medicine Oct 2022Hyperosmolar solutions are prescribed in neurosurgery patients to provide satisfactory intraoperative brain relaxation and to lower cerebral injuries related to surgical...
Clinical effectiveness of hypertonic sodium lactate infusion for intraoperative brain relaxation in patients undergoing scheduled craniotomy for supratentorial brain tumor resection: A study protocol of a single center double-blind randomized controlled phase II pilot trial.
INTRODUCTION
Hyperosmolar solutions are prescribed in neurosurgery patients to provide satisfactory intraoperative brain relaxation and to lower cerebral injuries related to surgical retractors. Mannitol is traditionally considered as the first-choice solution for brain relaxation in neurosurgery patients. Hypertonic sodium lactate infusion was reported to provide a higher and longer osmotic effect compared to mannitol in severely brain-injured patients and to prevent impaired cerebral energetics related to brain injuries. To date, the clinical effectiveness of hypertonic sodium lactate infusion has never been studied in neurosurgery patients. The hypothesis of the study is that hyperosmolar sodium lactate infusion may provide satisfactory intraoperative brain relaxation in patients undergoing scheduled craniotomy for supratentorial brain tumor resection.
METHODS AND ANALYSIS
We designed a phase II randomized, controlled, double-blind, single-center pilot trial, and aim to include 50 adult patients scheduled for craniotomy for supratentorial brain tumor resection under general anesthesia. Patients will be randomized to receive either mannitol (conventional group) or hypertonic sodium lactate (intervention group) infusion at the time of skin incision. Brain relaxation (primary outcome) will be assessed immediately after opening the dura by the neurosurgeon blinded to the treatment allocated using a validated 4-point scale. The primary outcome is the proportion of satisfactory brain relaxation, defined as brain relaxation score of 3 or 4.
ETHICS AND DISSEMINATION
This study was approved by the Ethics Committee (Comité de Protection des Personnes Est III) and authorized by the French Health Authority (Agence Nationale de Sécurité des Médicaments, Saint-Denis, France). The University Hospital of Besancon is the trial sponsor and the holder of all data and publication rights. Results of the study will be submitted for publication in a peer-review international medical journal and for presentation in abstract (oral or poster) in international peer-reviewed congresses.
REGISTRATION
The trial is registered with ClinicalTrials.gov (Identifier: NCT04488874, principal investigator: Prof Guillaume Besch, date of registration: July 28, 2020).
Topics: Adult; Brain; Clinical Trials, Phase II as Topic; Craniotomy; Double-Blind Method; Humans; Mannitol; Pilot Projects; Prospective Studies; Randomized Controlled Trials as Topic; Saline Solution, Hypertonic; Sodium Lactate; Supratentorial Neoplasms; Treatment Outcome
PubMed: 36221362
DOI: 10.1097/MD.0000000000031038