ArticleJournal of inflammation (London, England)2012
A new metabolomic assay to examine inflammation and redox pathways following LPS challenge.
Article in Journal of inflammation (London, England), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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Who cites it
10 citing papers in PubMed, 21 citations in OpenAlex.
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- Biochemical phenotyping of paroxysmal nocturnal hemoglobinuria reveals solute carriers and β-oxidation deficiencies.PloS one · 2023Article
- Evaluation of Anti-Inflammatory Effects of Celery Leaf and Stem Extracts in LPS-Induced RAW 264.7 Cells Using Nitric Oxide Assay and LC-MS Based Metabolomics.Current issues in molecular biology · 2021Article
- Metabolic characterisation of THP-1 macrophage polarisation using LC-MS-based metabolite profiling.Metabolomics : Official journal of the Metabolomic Society · 2020Article
- MyeloidJournal of immunology (Baltimore, Md. : 1950) · 2019Article
- Circulating adipocyte-derived exosomal MicroRNAs associated with decreased insulin resistance after gastric bypass.Obesity (Silver Spring, Md.) · 2017Article
- L-Arginine Availability and Metabolism Is Altered in Ulcerative Colitis.Inflammatory bowel diseases · 2016Article
- Sphingosine-1-phosphate in inflammatory bowel disease and colitis-associated colon cancer: the fat's in the fire.Translational cancer research · 2015Article
- Thiol/redox metabolomic profiling implicates GSH dysregulation in early experimental graft versus host disease (GVHD).PloS one · 2014Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelled
backgroundShifts in intracellular arginine (Arg) and sulfur amino acid (SAA) redox metabolism modulate macrophage activation, polarization and phenotype. Despite their importance in inflammation and redox regulatory pathways, comprehensive analysis of these metabolic networks was not previously possible with existing analytical methods.
methodsThe Arg/thiol redox LC-MS/MS metabolomics assay permits simultaneous assessment of amino acids and derivative products generated from Arg and SAA metabolism. Using this assay, LPS-induced changes in macrophage amino acid metabolism were monitored to identify pathway shifts during activation and their linkage to cellular redox regulation.
resultsMetabolite concentrations most significantly changed after treatment of a macrophage-like cell line (RAW) with LPS for 24 hrs were citrulline (Cit) (48-fold increase), ornithine (Orn) (8.5-fold increase), arginine (Arg) (66% decrease), and aspartic acid (Asp) (73% decrease). The ratio Cit + Orn/Arg + Asp (CO/AA) was more sensitive to LPS stimulation than other amino acid ratios commonly used to measure LPS-dependent inflammation (e.g., SAM/SAH, GSH/GSSG) and total media NOx. The CO/AA ratio was also the first ratio to change significantly after LPS treatment (4 hrs). Changes in the overall metabolomic profile over time indicated that metabolic pathways shifted from Arg catabolism to thiol oxidation.
conclusionsSimultaneous quantification of Arg and SAA metabolic pathway shifts following LPS challenge of macrophage indicate that, in this system, the Arg-Citrulline/NO cycle and arginase pathways are the amino acid metabolic pathways most sensitive to LPS-challenge. The cellular (Cit + Orn)/(Arg + Asp) ratio, which summarizes this pathway, was more responsive to lower concentrations of LPS and responded earlier than other metabolic biomarkers of macrophage activation including GSH redox. It is suggested that the CO/AA ratio is a redox- independent early biomarker of macrophage activation. The ability to measure both the CO/AA and GSH-redox ratios simultaneously permits quantification of the relative effects of LPS challenge on macrophage inflammation and oxidative stress pathways. The use of this assay in humans is discussed, as are clinical implications.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.