摘要
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 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 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-H(2)O(2)-chloride system under neuroinflammatory conditions results in oxidative attack of the total cerebral plasmalogen pool
- 出版日期2010-12-1
- 单位河北医科大学