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Global and targeted metabolomics characterizes antipsychotic medications, amino acid signatures, and platelet-activating factor involvement in first-episode psychosis

ABSTRACT: We performed global untargeted metabolomics by LCMS using a Q Exactive Focus mass spectrometer coupled to a Dionex U3000 UHPLC of plasma extract from patients following First Episode Psychosis. Both positive and negative reversed phase injections were performed in triplicate with replicates performed in separate batches. The Biocrates p400 kit was also used to obtain absolute quantification of 400+ metabolites using the vendor kit, column, and data processing tools as provided. The resulting global data was processed with Compound Discoverer 2.1. The resulting output is included within this upload as well as the output from the Biocrates data processing software. Data was integrated using a variety of R scripts as detailed in the associated manuscript.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Benjamin C Orsburn

PROVIDER: MSV000088371 | MassIVE | Fri Nov 12 05:16:00 GMT 2021

SECONDARY ACCESSION(S): PXD029695

REPOSITORIES: MassIVE

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Project description:This data series contains spotted oligo microarray data from 10 different experiments using Agilent Rat v2 microarrays. This data is being made public in support of Fillon S et al. Journal of Immunology, (2006). Proinflammatory bacterial components are at least partially responsible for causing the clinical features of sepsis, a syndrome that causes >100,000 deaths each year in the US (1). In the case of Gram positive infection, a key bacterial element recognized by the innate immune system is the cell wall, a complex network of peptidoglycan covalently linked to teichoic acids, proteins and lipoproteins. The current model of innate immune recognition of Gram positive bacteria suggests bacterial cell wall interacts with host recognition proteins, such as toll-like receptors (TLR) and Nod proteins. We describe an additional recognition system mediated by the platelet activating factor receptor (PAFr) and directed to the pathogen associated molecular pattern (PAMP) phosphorylcholine that results in uptake of bacterial components into host cells. Intravascular choline-containing cell walls bound to endothelial cells and caused rapid lethality in wild type, Tlr2-/- and Nod2-/- mice, but not in Pafr-/- mice. Cell wall exited the vasculature into the heart and brain, accumulating within endothelial cells, cardiomyocytes and neurons in a PAFr-dependent way. Physiological consequences of the cell wall/PAFr interaction were cell specific, being noninflammatory in endothelial cells and neurons, but causing rapid loss of cardiomyocyte contractility that contributed to death. Thus, PAFr shepherds phosphorylcholine-containing bacterial components such as cell wall into host cells from where the response ranges from quiescence to severe pathophysiology. Keywords: Competitive hybridizations The ten experiments in this series comprise of four distinct experiments, two of which were performed as biological triplicates and two as biological duplicates. The table below describes the overall design in detail: File Name Experiment 16011868017643v41_GEO_format.txt RBCEC Replicate 1 16011868017644v41_GEO_format.txt RBCEC Replicate 2 251186821865v41_GEO_format.txt Neuron Replicate 1 16011868021377v41_GEO_format.txt Neuron Replicate 2 251186821690v41_GEO_format.txt CW/Lyt44 Replicate 1 251186821691v41_GEO_format.txt CW/Lyt44 Replicate 2 251186821692v41_GEO_format.txt CW/Lyt44 Replicate 1 251186821693v41_GEO_format.txt CW+TNF/Lyt44+TNF Replicate 1 251186821694v41_GEO_format.txt CW+TNF/Lyt44+TNF Replicate 2 251186829677v41_GEO_format.txt CW+TNF/Lyt44+TNF Replicate 3

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Global and targeted metabolomics characterizes antipsychotic medications, amino acid signatures, and platelet-activating factor involvement in first-episode psychosis

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