Hypochlorous acid-mediated generation of glycerophosphocholine from unsaturated plasmalogen glycerophosphocholine lipids

Lessig, Jacqueline; Schiller, Jürgen; Arnhold, Jürgen; Fuchs, Beate

doi:10.1194/jlr.m600478-jlr200

Cited by 29 publications

(27 citation statements)

References 41 publications

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“…The aqueous phases of the extracts of the incubation mixture were also analyzed by MALDI-TOF MS (data not shown). New peaks corresponding to GPC appeared at m/z = 258.1 and 280.1 in the HOCl-treated samples [47] but were completely absent in the control sample (data not shown). This clearly indicates that GPC is a major oxidation product of plasmalogens particularly if an excess of HOCl is used.…”

Section: Artificial Mixture Of Choline Glycerophospholipidsmentioning

confidence: 68%

“…Therefore, the aim of this study was to extend the results of our previous study [47], where the preferred reactivity of the plasmalogen vinyl-ether group in comparison to olefinic residues was demonstrated. It is not yet known, whether the unsaturated 1-lysoPtdCho or an intact diacyl PtdCho exhibits a higher reactivity against HOCl.…”

mentioning

confidence: 88%

“…Free radical-induced oxidation of plasmalogen GPL with esterified docosahexaenoic acid (DHA) at the sn-2 position occurs at both, the sn-1 and sn-2 position, accompanied by the formation of glycerophosphocholine (GPC) [47]. Combined plasmalogen and 1-lysoPtdCho degradation and subsequent GPC generation could be demonstrated in artificial plasmalogens after HOCl-treatment, whereby marked GPC formation occurred only in the case of highly unsaturated 1-O-1 0 -stearenyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (SDHPC plasm ) and 1-O-1 0 -stearenyl-2-arachidonoyl-sn-glycero-3-phosphocholine (SAPC plasm ) [47]. However, these investigations are limited because there was only a single artificial plasmalogen as target for HOCl whereas under in vivo conditions there are many targets [47].…”

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confidence: 99%

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

Lessig¹,

Fuchs²

2009

Lipids

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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.

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Section: Artificial Mixture Of Choline Glycerophospholipidsmentioning

confidence: 68%

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confidence: 88%

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confidence: 99%

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

Lessig¹,

Fuchs²

2009

Lipids

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“…The observed transient accumulation of lysophospholipids in response to HOCl treatment is most likely a result of secondary modification reactions occurring at the remnant lysophospholipid, where chloramine formation at the ethanolamine headgroup [44], chlorohydrin formation in the alkene side chains [13], or sn-2 acyl abstraction [45,46] may be involved.…”

Section: Discussionmentioning

confidence: 99%

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

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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...

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“…Oxidation of LDL can be carried out by, among others, transition metals, hemoglobin, lipoxygenases, and reactive oxygen species generated by vascular endothelium or phagocytes, and HOCl can modify LDL at the lipid and the protein moieties in vitro and/or in vivo ( 13 ). Modifi ed lipids were preferentially identifi ed by MALDI-TOF-MS and 31 P NMR spectroscopy (40)(41)(42), while MALDI-TOF-MS, MS/MS, and LC-MS/MS are suitable techniques to identify the respective protein modifi cations basically after tryptic digestion ( 31,40 ). Here, we have used an LC-MS/ MS method with a high-resolution MS (a QTOF) to identify PTMs on tryptic peptides from delipidated apoB-100 samples ( 31 ) treated with HOCl added as reagent or were reported to be specifi c MPO-mediated modifi cations of apoB-100 ( 22,24 ).…”

Section: Discussionmentioning

confidence: 99%

Impact of myeloperoxidase-LDL interactions on enzyme activity and subsequent posttranslational oxidative modifications of apoB-100

Delporte

Boudjeltia

Noyon

et al. 2014

Journal of Lipid Research

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Over the past several years, considerable evidence has been obtained in support of the hypothesis that oxidants generated by the heme enzyme myeloperoxidase (MPO, EC1.11.2.2) play a key role in oxidation reaction of the artery wall. The enzyme, abundantly present in neutrophils and, to a lesser extent, in monocytes, is released during infl ammatory activation of immune cells. MPO produces hypochlorous acid (HOCl) by the reaction of hydrogen Abstract Oxidation of LDL by the myeloperoxidase (MPO)-H 2 O 2 -chloride system is a key event in the development of atherosclerosis. The present study aimed at investigating the interaction of MPO with native and modifi ed LDL and at revealing posttranslational modifi cations on apoB-100 (the unique apolipoprotein of LDL) in vitro and in vivo. Using amperometry, we demonstrate that MPO activity increases up to 90% when it is adsorbed at the surface of LDL. This phenomenon is apparently refl ected by local structural changes in MPO observed by circular dichroism. Using MS, we further analyzed in vitro modifi cations of apoB-100 by hypochlorous acid (HOCl) generated by the MPO-H 2 O 2 -chloride system or added as a reagent. A total of 97 peptides containing modifi ed residues could be identifi ed. Furthermore, differences were observed between LDL oxidized by reagent HOCl or HOCl generated by the MPO-H 2 O 2 -chloride system. Finally, LDL was isolated from patients with high cardiovascular risk to confi rm that our in vitro fi ndings are also relevant in vivo. We show that several HOCl-mediated modifi cations of apoB-100 identifi ed in vitro were also present on LDL isolated from patients who have increased levels of plasma MPO and MPO-modifi ed LDL. In conclusion, these data emphasize the specifi city of MPO to oxidize LDL. -Delporte,

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Hypochlorous acid-mediated generation of glycerophosphocholine from unsaturated plasmalogen glycerophosphocholine lipids

Cited by 29 publications

References 41 publications

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

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

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

Impact of myeloperoxidase-LDL interactions on enzyme activity and subsequent posttranslational oxidative modifications of apoB-100

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