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

Daniel Scherr

Gerhard Pichler

Roland Malli

Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid Stoffw Microb

Halasiddappa, LM; Koefeler, H; Futerman, AH; Hermetter, A.
Oxidized phospholipids induce ceramide accumulation in RAW 264.7 macrophages: role of ceramide synthases.
PLoS One. 2013; 8(7):e70002-e70002 Doi: 10.1371/journal.pone.0070002 [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

Co-Autor*innen der Med Uni Graz: Köfeler Harald
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Abstract:: Oxidized phospholipids (OxPLs), including 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) and 1-palmitoyl-2-oxovaleroyl-sn-glycero-3-phosphocholine (POVPC) are among several biologically active derivatives that are generated during oxidation of low-density lipoproteins (LDLs). These OxPLs are factors contributing to pro-atherogenic effects of oxidized LDLs (OxLDLs), including inflammation, proliferation and death of vascular cells. OxLDL also elicits formation of the lipid messenger ceramide (Cer) which plays a pivotal role in apoptotic signaling pathways. Here we report that both PGPC and POVPC are cytotoxic to cultured macrophages and induce apoptosis in these cells which is associated with increased cellular ceramide levels after several hours. In addition, exposure of RAW 264.7 cells to POVPC and PGPC under the same conditions resulted in a significant increase in ceramide synthase activity, whereas, acid or neutral sphingomyelinase activities were not affected. PGPC is not only more toxic than POVPC, but also a more potent inducer of ceramide formation by activating a limited subset of CerS isoforms. The stimulated CerS activities are in line with the C16-, C22-, and C24:0-Cer species that are generated under the influence of the OxPL. Fumonisin B1, a specific inhibitor of CerS, suppressed OxPL-induced ceramide generation, demonstrating that OxPL-induced CerS activity in macrophages is responsible for the accumulation of ceramide. OxLDL elicits the same cellular ceramide and CerS effects. Thus, it is concluded that PGPC and POVPC are active components that contribute to the capacity of this lipoprotein to elevate ceramide levels in macrophages.
Find related publications in this database (using NLM MeSH Indexing): Animals -; Apoptosis - drug effects; Cell Line -; Cell Survival - drug effects; Ceramides - metabolism; Enzyme Activation - drug effects; Flow Cytometry -; Gene Expression Regulation, Enzymologic - drug effects; Isoenzymes - genetics; Lipoproteins, LDL - chemistry; Macrophages - cytology; Mice -; Oxidation-Reduction -; Oxidoreductases - genetics; Phospholipid Ethers - pharmacology; Phospholipids - chemistry; Reverse Transcriptase Polymerase Chain Reaction -