Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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"Köpfe" der aktuellen Meldungen:

Nina Höller

Nariae Baik-Schneditz

Bernhard Schwaberger

Lukas Peter Mileder

Niels Hammer

Gerhard Pichler

Roland Malli

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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Bretscher, P; Egger, J; Shamshiev, A; Trötzmüller, M; Köfeler, H; Carreira, EM; Kopf, M; Freigang, S.
Phospholipid oxidation generates potent anti-inflammatory lipid mediators that mimic structurally related pro-resolving eicosanoids by activating Nrf2.
EMBO Mol Med. 2015; 7(5):593-607 Doi: 10.15252/emmm.201404702 [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

Co-Autor*innen der Med Uni Graz: Köfeler Harald; Trötzmüller Martin
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Abstract:: Exposure of biological membranes to reactive oxygen species creates a complex mixture of distinct oxidized phospholipid (OxPL) species, which contribute to the development of chronic inflammatory diseases and metabolic disorders. While the ability of OxPL to modulate biological processes is increasingly recognized, the nature of the biologically active OxPL species and the molecular mechanisms underlying their signaling remain largely unknown. We have employed a combination of mass spectrometry, synthetic chemistry, and immunobiology approaches to characterize the OxPL generated from the abundant phospholipid 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PAPC) and investigated their bioactivities and signaling pathways in vitro and in vivo. Our study defines epoxycyclopentenones as potent anti-inflammatory lipid mediators that mimic the signaling of endogenous, pro-resolving prostanoids by activating the transcription factor nuclear factor E2-related factor 2 (Nrf2). Using a library of OxPL variants, we identified a synthetic OxPL derivative, which alleviated endotoxin-induced lung injury and inhibited development of pro-inflammatory T helper (Th) 1 cells. These findings provide a molecular basis for the negative regulation of inflammation by lipid peroxidation products and propose a novel class of highly bioactive compounds for the treatment of inflammatory diseases. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.
Find related publications in this database (using NLM MeSH Indexing): Animals -; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - metabolism; Cyclopentanes - chemistry; Cyclopentanes - metabolism; Eicosanoids - chemistry; Eicosanoids - metabolism; Epoxy Compounds - chemistry; Epoxy Compounds - metabolism; Lung - pathology; Mice, Inbred C57BL -; Mice, Knockout -; NF-E2-Related Factor 2 - metabolism; Oxidation-Reduction -; Phospholipid Ethers - metabolism; Th1 Cells - immunology
Find related publications in this database (Keywords): inflammation; isoprostanes; lung injury; Nrf2; oxidized phospholipids