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  • Mouse brain plasmalogens are targets for hypochlorous acid-mediated modification in vitro and in vivo.

Mouse brain plasmalogens are targets for hypochlorous acid-mediated modification in vitro and in vivo.

Free radical biology & medicine (2010-09-03)
Andreas Ullen, Günter Fauler, Harald Köfeler, Sabine Waltl, Christoph Nusshold, Eva Bernhart, Helga Reicher, Hans-Jörg Leis, Andrea Wintersperger, Ernst Malle, Wolfgang Sattler
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.

MATERIALS
Product Number
Brand
Product Description

Avanti
17:0-14:1 PI, Avanti Research - A Croda Brand LM1504, methanol solution
Avanti
17:0-20:4 PE, Avanti Research - A Croda Brand LM1102, methanol solution
Avanti
17:0-14:1 PC, Avanti Research - A Croda Brand LM1004, methanol solution