Selective plasmenylcholine oxidation by hypochlorous acid: formation of lysophosphatidylcholine chlorohydrins

Messner, Maria C.; Albert, Carolyn J.; Hsu, Fong‐Fu; Ford, David A.

doi:10.1016/j.chemphyslip.2006.06.003

Cited by 30 publications

(35 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3B). In addition to 2-ClHDA we could detect other 2-chloro fatty aldehydes generated by HOCl attack of plasmalogen subspecies [37]. Depending on the alkenyl residue present in the sn-1 position either 2-chlorooctadecanal (from C18:0) or 2-chlorooctadecenal (from C18:1) was formed (Fig.…”

Section: Modification Of Phosphoethanolamines and Phosphocholines In mentioning

confidence: 89%

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

Üllen

Fauler

Köfeler

et al. 2010

Free Radical Biology and Medicine

View full text Add to dashboard Cite

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.© 2010 Elsevier Inc. All rights reserved. * Corresponding author. Fax: +43 316 380 9615. wolfgang.sattler@medunigraz.at. The mammalian brain is particularly sensitive toward oxidative damage, a result of the high oxygen demand and the high content of unsaturated lipids in the central nervous system (CNS) [1]. Potential sources of reactive species in the brain are mitochondria, amyloid-β peptides, redox-active iron, the NADPH-oxidase complex, and myeloperoxidase (MPO) [1][2][3]. MPO, a member of the heme peroxidase family, is present in the azurophilic granules of phagocytes, and H 2 O 2 -dependent oxidation of chloride ions to the powerful oxidant hypochlorous acid/hypochlorite (HOCl/OCl − ) is catalyzed by MPO. Under physiological conditions MPO-generated oxidants play an important role in killing invading pathogens, thereby contributing to host defense [3]. However, chronic activation of MPO results in elevated levels of reactive species, favoring chloramine formation, a modification potentially leading to tissue and/or organ injury [4][5][6][7][8]. Increasing evidence points toward MPO as a disease-amplifying enzyme in neurodegeneration [2]. In multiple sclerosis, MPO is present in microglia/macrophages at lesion sites [9,10] and cortical demyelination is associa...

show abstract

Section: Modification Of Phosphoethanolamines and Phosphocholines In mentioning

confidence: 89%

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

Üllen

Fauler

Köfeler

et al. 2010

Free Radical Biology and Medicine

View full text Add to dashboard Cite

show abstract

“…The same is true for the use of the neutral loss of 36 Da (H 35 Cl), which has been suggested as diagnostic for chlorinated ions such as chlorohydrins of PCs. The presence of chlorine can be checked by neutral loss of 38 Da for the isotopic H 37 Cl form; this profile should match that of neutral loss of 36 Da, although weaker owing to the 35 Cl: 37 Cl isotope ratio (78,92). However, caution is required, as bis-hydroperoxides may also undergo sequential loss of two water molecules, corresponding to a decrease of 36 Da (50).…”

Section: Application Of Targeted Ms Methods For Oxidized Phospholipidsmentioning

confidence: 99%

Oxidative Lipidomics Coming of Age: Advances in Analysis of Oxidized Phospholipids in Physiology and Pathology

Spickett

Pitt

2015

Antioxidants & Redox Signaling

102

View full text Add to dashboard Cite

Significance: Oxidized phospholipids are now well recognized as markers of biological oxidative stress and bioactive molecules with both pro-inflammatory and anti-inflammatory effects. While analytical methods continue to be developed for studies of generic lipid oxidation, mass spectrometry (MS) has underpinned the advances in knowledge of specific oxidized phospholipids by allowing their identification and characterization, and it is responsible for the expansion of oxidative lipidomics. Recent Advances: Studies of oxidized phospholipids in biological samples, from both animal models and clinical samples, have been facilitated by the recent improvements in MS, especially targeted routines that depend on the fragmentation pattern of the parent molecular ion and improved resolution and mass accuracy.

show abstract

“…The marked reactivity of this group renders plasmalogens subject to oxidation and imparts potentially strong antioxidative properties to these phospholipids [1,2]. Compared to their 1-acyl analogues, plasmalogens are more susceptible to oxidative damage [3,4]. Therefore, their supposed function as ''scavengers'' [5] can be explained by the direct reaction between atmospheric oxygen or-in particular-reactive oxygen species (ROS) and the vinyl-ether moiety [5,6].…”

mentioning

confidence: 99%

“…Double bonds of the fatty acyl residue present in the sn-2 position of the resulting lysoPtdCho are secondary HOCl targets leading to the production of lysoPtdCho-chlorohydrins. Unsaturated lysoPtdCho species are also more susceptible to oxidative attack than unsaturated PtdCho [4]. The preferred destruction of plasmenyl-phospholipids in membranes under oxidative stress is one possible explanation of the physiological function of these compounds in membranes: Plasmalogens are supposed to protect animal cells against oxidative damage [2,5,6,[8][9][10][11], and are regarded as natural antioxidants in lipoproteins [2].…”

mentioning

confidence: 99%

HOCl‐Mediated Glycerophosphocholine and Glycerophosphoethanolamine Generation from Plasmalogens in Phospholipid Mixtures

Lessig¹,

Fuchs²

2009

Lipids

View full text Add to dashboard Cite

Many mammalian tissues and cells contain, in addition to (diacyl) phospholipids, considerable amounts of plasmalogens, which may function as important antioxidants. Apart from the "scavenger" function mediated by the high sensitivity of the vinyl-ether bond, the functional role of plasmalogens is so far widely unknown. Furthermore, there is increasing evidence that plasmalogen degradation products have harmful effects in inflammatory processes. In a previous investigation glycerophosphocholine (GPC) formation was verified as a novel plasmalogen degradation pathway upon oxidation with hypochlorous acid (HOCl), however these investigations were performed in simple model systems. Herein, we examine plasmalogen degradation in a more complex system in order to evaluate if GPC generation is also a major pathway in the presence of other highly unsaturated glycerophospholipids (GPL) representing an additional reaction site of HOCl targets. Using MALDI-TOF mass spectrometry and (31)P NMR spectroscopy, we confirmed that the first step of the HOCl-induced degradation of GPL mixtures containing plasmalogens is the attack of the vinyl-ether bond resulting in the generation of 1-lysophosphatidylcholine (lysoPtdCho) or 1-lysophosphatidylethanolamine. In the second step HOCl reacts with the fatty acyl residue in the sn-2 position of 1-lysoPtdCho. This reaction is about three times faster in comparison to comparable diacyl-GPL. Thus, the generation of GPC and glycerophosphoethanolamine (GPE) from plasmalogens are relevant products formed from HOCl attack on the vinyl-ether bond of plasmalogens under pathological conditions.

show abstract

Selective plasmenylcholine oxidation by hypochlorous acid: formation of lysophosphatidylcholine chlorohydrins

Cited by 30 publications

References 33 publications

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

Oxidative Lipidomics Coming of Age: Advances in Analysis of Oxidized Phospholipids in Physiology and Pathology

HOCl‐Mediated Glycerophosphocholine and Glycerophosphoethanolamine Generation from Plasmalogens in Phospholipid Mixtures

Contact Info

Product

Resources

About