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Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Ullen, A; Fauler, G; Köfeler, H; Waltl, S; Nusshold, C; Bernhart, E; Reicher, H; Leis, HJ; Wintersperger, A; Malle, E; Sattler, W.
Mouse brain plasmalogens are targets for hypochlorous acid-mediated modification in vitro and in vivo.
Free Radic Biol Med. 2010; 49(11):1655-1665 [OPEN ACCESS]
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Autor/innen der Med Uni Graz:
Bernhart Eva Maria
Fauler Günter
Köfeler Harald
Leis Hans-Jörg
Malle Ernst
Nusshold Christoph
Reicher Helga
Sattler Wolfgang
Üllen Andreas
Waltl Sabine Evelyn
Wintersperger Andrea
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Number of Figures: 7
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Abstract:
Plasmalogens, 1-O-alk-1'-enyl-2-acyl-sn-glycerophospholipids, are significant constituents of cellular membranes and are essential for normal brain development. Plasmalogens, which contain a vinyl ether bond at the sn-1 position, are preferential targets for hypochlorous acid (HOCl), generated by myeloperoxidase (MPO) from H(2)O(2) and chloride ions. Because MPO is implicated in neurodegeneration, this study pursued two aims: (i) to investigate the reactivity of mouse brain plasmalogens toward HOCl in vitro and (ii) to obtain in vivo evidence for MPO-mediated brain plasmalogen modification. Liquid chromatography coupled to hybrid linear ion trap-Fourier transform-ion cyclotron resonance mass spectrometry revealed plasmalogen modification in mouse brain lipid extracts at lower HOCl concentrations as observed for diacylphospholipids, resulting in the generation of 2-chloro fatty aldehydes and lysophospholipids. Lysophosphatidylethanolamine accumulation was transient, whereas lysophosphatidylcholine species containing saturated acyl residues remained stable. In vivo, a single, systemic endotoxin injection resulted in upregulation of cerebral MPO mRNA levels to a range comparable to that observed for tumor necrosis factor-α and cyclooxygenase-2. This inflammatory response was accompanied by a significant decrease in several brain plasmalogen species and concomitant in vivo generation of 2-chlorohexadecanal. The present findings demonstrate that activation of the MPO-H(2)O(2)-chloride system under neuroinflammatory conditions results in oxidative attack of the total cerebral plasmalogen pool. As this lipid class is indispensable for normal neuronal function, HOCl-mediated plasmalogen modification is likely to compromise normal synaptic transmission.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Brain - drug effects
Brain Chemistry - drug effects
Cells, Cultured -
Ethanolamines - analysis
Hypochlorous Acid - pharmacology
Inflammation Mediators - metabolism
Lipopolysaccharides - pharmacology
Male -
Mice -
Mice, Inbred C57BL -
Oxidation-Reduction -
Phospholipids - analysis
Phosphorylcholine - analysis
Plasmalogens - chemistry
Transcription, Genetic - drug effects

Find related publications in this database (Keywords)
Chlormative stress
Endotoxin
Hypochlorite
Lipotoxicity
Myeloperoxidase
Neuroinflammation
Free radicals
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