Biology subjects

Hagn, G.

Publications and source records attributed to Hagn, G..

3 recordsLinked to original sources

bioRxiv2025

Integrated tissue proteomics and lipidomics from ovine organs suggests novel functional implications for fatty acids and lipid mediators.

Lipid mediators are potent biomolecules that may help to gain specific information about biological processes. However, due to incomplete functional annotations and hence interpretive challenges these molecules are hardly considered in molecular profiling experiments. We hypothesized that correlating lipid mediators extracted from tissues with corresponding proteomics data and the corresponding Gene Ontology terms characteristic of specific tissue types could enable functional annotation of these lipids. Thirteen organs and tissues from sheep (Ovis aries) were analyzed using mass spectrometry-based untargeted proteomics and lipidomics. In total, 4717 proteins and 166 free fatty acids, oxylipins, lysolipids, endocannabinoids, and bile acids were catalogued. This included the previously uncharacterized oxylipin 4-hydroxy-eicosatetraenoic acid (4-HETE), whose identity was confirmed by chemical synthesis. Co-expression and clustering analyses validated our hypothesis, successfully reproducing known and suggesting novel lipid mediator functions. Tissue levels of polyunsaturated fatty acids (PUFAs) correlated with pro-resolving mediators and, unexpectedly, with the cellular protein synthesis and folding machinery. These findings suggest that PUFAs and their derivatives support protein synthesis fidelity and efferocytosis, both essential contributors for the effective resolution of inflammation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=143 SRC="FIGDIR/small/685055v2_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@126b41org.highwire.dtl.DTLVardef@13fa9adorg.highwire.dtl.DTLVardef@9ccaa1org.highwire.dtl.DTLVardef@1bb429b_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstract:C_FLOATNO The Figure was partly generated using Servier Medical Art, provided by Servier, licensed under a Creative Commons Attribution 3.0 Unported license. C_FIG

systems biology↗

bioRxiv2024

Phosphoproteomics highlights complex resource management upon inflammatory stimulation of fibroblasts

The stimulation of cells by inflammatory mediators gives rise to intricate signaling cascades, inducing specific biological functions. The role of kinase activation for the establishment of specific inflammatory functions has only scarcely been established. A time-course analysis of human fetal fibroblasts stimulated with Interleukin-1{beta} (IL-1{beta}) and/or Dexamethasone (Dex) was conducted using mass spectrometry-based proteomics and phosphoproteomics in conjunction with lysolipid and oxylipin profiling. The IL-1{beta} induced proteome alterations indicated metabolic, transcriptional, and translational activation, including inflammatory marker proteins such as NOS1, THBS1, and STING1. The induction of mitochondrial proteins and the formation of numerous lysolipids indicated an increase in beta-oxidation. In addition to the NF-{kappa}B and STAT signaling pathways, which are characteristic of inflammatory activation, the MAP and AKT kinase signaling pathways were found to be strongly induced. Six hours after treatment, the observed signaling events exhibited a notable decline, nearly returning to their initial states after 24 hours. It is noteworthy that nearly all of these signaling activities were also observed in cells treated with Dex alone. Additionally, the proteome exhibited transient alterations, which included proteins otherwise characteristic of an inflammatory response, such as MMP3 and NFKB2. Activation of the kinase PIKFYVE was apparently specific for dexamethasone but constituted a minority of the total phosphorylation events. Only after 24 hours was the induction of proteins characteristic of glucocorticoids, such as TSC22D3 and MAOA, observed. The analysis of the effects of dexamethasone on the background of established inflammatory signaling verified the known inhibitory functions and resulted in the expression of anti-inflammatory proteins and oxylipins, but hardly affected the signaling events involving MAP and AKT kinases. In conclusion, this data demonstrates that a majority of inflammation-associated signaling events in fibroblasts needs to be attributed to resource and stress management rather than the establishment of specific inflammatory effector functions.

biochemistry↗

bioRxiv2023

Multilevel Omics-Readouts of in vitro Perturbation Studies are Determined by Memory Effects from Subculture

Mass spectrometry-based omics technologies are increasingly used to map drug effects to biological pathways by identifying significant molecular events. Significance is influenced by the effect size and the variation of each molecular parameter. While the former is largely determined by the biological system, the latter can be tuned by the experimental workflow. Here, we unequivocally show that memory effects originating from subculture of colon carcinoma cells before treating with arsenic trioxide exacerbate the variation of multiple omics levels, including eicosadomics, proteomics and phosphoproteomics, without necessarily impacting on effect size. Real-time monitoring of individual samples enables control over subculture homogeneity and improves the median variation >2-fold across omics levels. This considerably facilitated mode of action deconvolution and resulted in a bilevel perturbation network of 321 causal conjectures. Controlling memory effects from subculture revealed key signaling cascades and transcriptional regulatory events that extend the molecular understanding of arsenic trioxide in solid tumors.

systems biology↗