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

Plasmalogens 1-O-alk-1'-enyl-2-acyl sn-glycerophospholipids are significant constituents of cellular membianes and are essential for normal brain development Plasmalogens which contain a vinyl ether bond at the sn 1 position are preferential targets for hypochloious acid (HOCI) generated by myeloperoxidase (MPO) from H2O2 and chloride ions Because MPO is implicated in neurodegeneration this study pursued two aims ( I) to investigate the reactivity of mouse brain plasmalogens toward HOCI in vitro and (n) to obtain in vivo evidence for MPO-mediated brain plasmalogen modification Liquid chromatography coupled to hybrid lineal ion trap-Fourier transform-ion cyclotron resonance mass spectrometry revealed plasmalogen modification in mouse brain lipid extracts at lower HOC concentrations as observed for diacylphospholipids resulting in the generation of 2 chloio 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 a and cyclooxygenase-2 This inflammatory response was accompanied by a significant decrease in several brain plasmalogen species and concomitant in vivo generation of 2-chlowhexadecanal The present findings demonstrate that activation of the MPO-H2O2-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 HOCI mediated plasmalogen modification is likely to compromise normal synaptic transmission (C) 2010 Elsevier Inc All rights reserved