-
Nutrients Mar 2023(1) Background: Exercise is effective in promoting and maintaining bone mass. The aim of this study was to detect the exercise-induced metabolic changes in bone tissue...
(1) Background: Exercise is effective in promoting and maintaining bone mass. The aim of this study was to detect the exercise-induced metabolic changes in bone tissue of zebrafish. (2) Methods: Thirty-eight zebrafish (Danio rerio, six months old) were analyzed. The exercise group ( = 19) received 8 weeks of counter-current swimming training. The control group ( = 19) was not subjected to exercise. Mineralization was quantified, and alkaline phosphatase (Alp) and anti-tartrate acid phosphatase (Trap) activities were estimated ( = 12). The metabolomics ( = 12) and transcriptomics ( = 14) data of bone tissue were used for the integration analyses. (3) Results: The results showed that the exercise training improved the bone mineralization of zebrafish, e.g., the exercise group (5.74 × 10 ± 7.63 × 10) had a higher mean optical density than the control group (5.26 × 10 ± 8.56 × 10, = 0.046) for the caudal vertebrae. The amount of mineralized matrix in scales of the exercised zebrafish was also higher (0.156 ± 0.012 vs. 0.102 ± 0.003, = 0.005). Both histological staining and biochemical analysis revealed increased Alp activity (0.81 ± 0.26 vs. 0.76 ± 0.01, = 0.002) and decreased Trap activity (1.34 ± 0.01 vs. 1.36 ± 0.01, = 0.005) in the exercise group. A total of 103 different metabolites (DMs, VIP ≥ 1, fold change (FC) ≥ 1.20 or ≤0.83, < 0.050) were identified. Alanine, aspartate and glutamate metabolism, β-alanine metabolism, pyrimidine metabolism, and pantothenate and CoA biosynthesis were the significantly enriched metabolic pathways ( < 0.050). A total of 35 genes ( ≤ 0.050 (BH), |Log2FC| ≥ 0.5) were coenriched with the 103 DMs in the four identified pathways. Protein-protein interaction network analysis of the 35 genes showed that , , and were the core genes. (4) Conclusions: The results of this study suggest that alanine, aspartate and glutamate metabolism, β-alanine metabolism, pyrimidine metabolism, and pantothenate and CoA biosynthesis contributed to exercise-induced improvements in bone mass.
Topics: Animals; Zebrafish; Transcriptome; Aspartic Acid; Metabolomics; Alanine; beta-Alanine; Pyrimidines; Glutamates
PubMed: 37049535
DOI: 10.3390/nu15071694 -
International Journal of Molecular... Jun 2023d-amino acids have recently been found to be present in the extracellular milieu at millimolar levels and are therefore assumed to play a physiological function....
d-amino acids have recently been found to be present in the extracellular milieu at millimolar levels and are therefore assumed to play a physiological function. However, the pathway (or potential pathways) by which these d-amino acids are secreted remains unknown. Recently, has been found to possess one or more energy-dependent d-alanine export systems. To gain insight into these systems, we developed a novel screening system in which cells expressing a putative d-alanine exporter could support the growth of d-alanine auxotrophs in the presence of l-alanyl-l-alanine. In the initial screening, five d-alanine exporter candidates, AlaE, YmcD, YciC, YraM, and YidH, were identified. Transport assays of radiolabeled d-alanine in cells expressing these candidates indicated that YciC and AlaE resulted in lower intracellular levels of d-alanine. Further detailed transport assays of AlaE in intact cells showed that it exports d-alanine in an expression-dependent manner. In addition, the growth constraints on cells in the presence of 90 mM d-alanine were mitigated by the overexpression of AlaE, implying that AlaE could export free d-alanine in addition to l-alanine under conditions in which intracellular d/l-alanine levels are raised. This study also shows, for the first time, that YciC could function as a d-alanine exporter in intact cells.
Topics: Escherichia coli; Alanine; Escherichia coli Proteins; Amino Acids; Biological Transport; Amino Acid Transport Systems, Neutral
PubMed: 37373388
DOI: 10.3390/ijms241210242 -
Biomolecules Jan 2022Neutral amino acid transporters ASCT1 and ASCT2 are two SLC1 (solute carrier 1) family subtypes, which are specific for neutral amino acids. The other members of the...
Neutral amino acid transporters ASCT1 and ASCT2 are two SLC1 (solute carrier 1) family subtypes, which are specific for neutral amino acids. The other members of the SLC1 family are acidic amino acid transporters (EAATs 1-5). While the functional similarities and differences between the EAATs have been well studied, less is known about how the subtypes ASCT1 and 2 differ in kinetics and function. Here, by performing comprehensive electrophysiological analysis, we identified similarities and differences between these subtypes, as well as novel functional properties, such as apparent substrate affinities of the inward-facing conformation (in the range of 70 μM for L-serine as the substrate). Key findings were: ASCT1 has a higher apparent affinity for Na, as well as a larger [Na] dependence of substrate affinity compared to ASCT2. However, the general sequential Na/substrate binding mechanism with at least one Na binding first, followed by amino acid substrate, followed by at least one more Na ion, appears to be conserved between the two subtypes. In addition, the first Na binding step, presumably to the Na3 site, occurs with high apparent affinity (<1 mM) in both transporters. In addition, ASCT1 and 2 show different substrate selectivities, where ASCT1 does not respond to extracellular glutamine. Finally, in both transporters, we measured rapid, capacitive charge movements upon application and removal of amino acid, due to rearrangement of the translocation equilibrium. This charge movement decays rapidly, with a time constant of 4-5 ms and recovers with a time constant in the 15 ms range after substrate removal. This places a lower limit on the turnover rate of amino acid exchange by these two transporters of 60-80 s.
Topics: Alanine; Amino Acid Transport System ASC; Cysteine; Kinetics; Serine
PubMed: 35053261
DOI: 10.3390/biom12010113 -
Clinical and Translational Science Apr 2022
Topics: Adenosine Monophosphate; Alanine; Cardiovascular Diseases; Drug-Related Side Effects and Adverse Reactions; Humans; Pharmacovigilance; Product Surveillance, Postmarketing
PubMed: 35303401
DOI: 10.1111/cts.13261 -
European Review For Medical and... Jul 2021The purpose of this narrative review is to discuss the available information regarding the currently utilized COVID-19 therapies (and the evidence level supporting them)... (Review)
Review
OBJECTIVE
The purpose of this narrative review is to discuss the available information regarding the currently utilized COVID-19 therapies (and the evidence level supporting them) and opioids for chronic pain with a focus on warnings of potential interactions between these two therapeutic approaches.
MATERIALS AND METHODS
Papers were retrieved from a PubMed search, using different combinations of keywords [e.g., pain treatment AND COVID-19 AND drug-drug interaction (DDI)], without limitations in terms of publication date and language.
RESULTS
Remdesivir is an inhibitor of CYP3A4 and may increase the plasma concentration of CYP3A4 substrates (e.g., fentanyl). Dexamethasone is an inducer of CYP3A4 and glycoprotein P, thus coadministration with drugs metabolized by this isoform will lead to their increased clearance. Dexamethasone may cause hypokalemia, thus potentiating the risk of ventricular arrhythmias if it is given with opioids able to prolong the QT interval, such as oxycodone and methadone. Finally, the existing differences among opioids with regard to their impact on immune responses should also be taken into account with only tapentadol and hydromorphone appearing neutral on both cytokine production and immune parameters.
CONCLUSIONS
Clinicians should keep in mind the frequent DDIs with drugs extensively metabolized by the CYP450 system and prefer opioids undergoing a limited hepatic metabolism. Identification and management of DDIs and dissemination of the related knowledge should be a major goal in the delivery of chronic care to ensure optimized patient outcomes and facilitate updating recommendations for COVID-19 therapy in frail populations, namely comorbid, poly-medicated patients or individuals suffering from substance use disorder.
Topics: Adenosine Monophosphate; Alanine; Analgesics, Opioid; Anti-Inflammatory Agents; Antiviral Agents; Chronic Pain; Dexamethasone; Drug Interactions; Humans; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34337735
DOI: 10.26355/eurrev_202107_26399 -
Journal of Investigational Allergology... Jun 2023
Topics: Humans; Drug Hypersensitivity; Skin Tests; Alanine; Hypersensitivity, Delayed; Hypersensitivity, Immediate
PubMed: 35834314
DOI: 10.18176/jiaci.0844 -
The Lancet. Infectious Diseases Dec 2021
Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Humans; Randomized Controlled Trials as Topic; SARS-CoV-2; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 34838222
DOI: 10.1016/S1473-3099(21)00695-2 -
The Lancet. Infectious Diseases Dec 2021
Topics: Adenosine Monophosphate; Alanine; Humans
PubMed: 34838223
DOI: 10.1016/S1473-3099(21)00693-9 -
CMAJ : Canadian Medical Association... Jan 2021
Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Chemical and Drug Induced Liver Injury; Critical Care; Drug Hypersensitivity; Humans; SARS-CoV-2; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 33408097
DOI: 10.1503/cmaj.202505 -
Analytical Chemistry Jan 2024Lanthipeptides make up a large group of natural products that belong to the ribosomally synthesized and post-translationally modified peptides (RiPPs). Lanthipeptides...
Lanthipeptides make up a large group of natural products that belong to the ribosomally synthesized and post-translationally modified peptides (RiPPs). Lanthipeptides contain lanthionine and methyllanthionine bis-amino acids that have varying stereochemistry. The stereochemistry of new lanthipeptides is often not determined because current methods require equipment that is not standard in most laboratories. In this study, we developed a facile, efficient, and user-friendly method for detecting lanthipeptide stereochemistry, utilizing advanced Marfey's analysis with detection by liquid chromatography coupled with mass spectrometry (LC-MS). Under optimized conditions, 0.05 mg of peptide is sufficient to characterize the stereochemistry of five (methyl)lanthionines of different stereochemistry using a simple liquid chromatography setup, which is a much lower detection limit than current methods. In addition, we describe methods to readily access standards of the three different methyllanthionine stereoisomers and two different lanthionine stereoisomers that have been reported in known lanthipeptides. The developed workflow uses a commonly used nonchiral column system and offers a scalable platform to assist antimicrobial discovery. We illustrate its utility with an example of a lanthipeptide discovered by genome mining.
Topics: Peptides; Sulfides; Alanine; Chromatography, Liquid
PubMed: 38232355
DOI: 10.1021/acs.analchem.3c04958