Metabolism of Myeloperoxidase-derived 2-Chlorohexadecanal

Wildsmith, Kristin R.; Albert, Carolyn J.; Anbukumar, Dhanalakshmi S.; Ford, David A.

doi:10.1074/jbc.m602505200

Cited by 50 publications

(73 citation statements)

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“…Previous studies have examined the metabolism of ␣ -ClFALD produced in PMA-stimulated neutrophils to ␣ -ClFA and ␣ -ClFOH ( 17,18 ). In those studies, both ␣ -ClFA and ␣ -ClFOH were elevated 15 min following PMA stimulation, although ␣ -ClFALD was elevated as early as 5 min.…”

Section: Discussionmentioning

confidence: 99%

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Identification of glutathione adducts of α-chlorofatty aldehydes produced in activated neutrophils

Duerr

Aurora

Ford

2015

Journal of Lipid Research

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Section: Discussionmentioning

confidence: 99%

“…10A ). 2-ClHA and 2-ClOA are the oxidation products of 2-ClHDA and 2-ClODA ( 17,18 ). Furthermore, the GSH adducts of 2-ClHDA and 2-ClODA, HDA-GSH and ODA-GSH, are elevated in the plasma of K/BxN mice ( Fig.…”

Section: Elevations In Plasma ␣ -Clfa and Fald-gsh In K/bxn Micementioning

confidence: 99%

Identification of glutathione adducts of α-chlorofatty aldehydes produced in activated neutrophils

Duerr

Aurora

Ford

2015

Journal of Lipid Research

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“…FALDH (classified as ALDH3A2; SwissProt P51648) is expressed in brain and when mutated or absent causes severe neurological symptoms [58]. Alternatively, oxidation of 2-ClHDA to 2-chlorohexadecanoic acid and subsequent incorporation into the polar lipid fraction could redirect 2-ClHDA via 2-chlorohexadecanoic acid into an inert and stable storage pool [59]. Finally, Schiff base formation between 2-chloro fatty aldehydes and ethanolamine-containing glycerophospholipids and/or the ε-amino group of protein lysine residues [60,61] could account for the observed time-dependent decrease in cerebral 2-ClHDA concentrations (Fig.…”

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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“…Plasmalogens are phospholipids found in many tissues, especially in the nervous, immune, and cardiovascular systems, including cardiomyocytes, endothelial, and VSMCs [137]. HOCl reacts with the vinyl ether group of plasmalogens, releasing α-chlorofatty aldehydes such as 2-chlorohexadecanal [138] which can be metabolized further to 2-chlorofatty acids and 2-chlorofatty alcohols [139]. Using mass spectrometry, several of these metabolites have been detected in human atheroma and LDL isolated from it [50,140], while further downstream metabolites such as 2-chloradipic acid have been detected in the urine of humans [141].…”

Section: Surrogate Biomarkersmentioning

confidence: 99%

The roles of myeloperoxidase in coronary artery disease and its potential implication in plaque rupture

et al. 2016

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Atherosclerosis is the main pathophysiological process underlying coronary artery disease (CAD). Acute complications of atherosclerosis, such as myocardial infarction, are caused by the rupture of vulnerable atherosclerotic plaques, which are characterized by thin, highly inflamed, and collagen-poor fibrous caps. Several lines of evidence mechanistically link the heme peroxidase myeloperoxidase (MPO), inflammation as well as acute and chronic manifestations of atherosclerosis. MPO and MPO-derived oxidants have been shown to contribute to the formation of foam cells, endothelial dysfunction and apoptosis, the activation of latent matrix metalloproteinases, and the expression of tissue factor that can promote the development of vulnerable plaque. As such, detection, quantification and imaging of MPO mass and activity have become useful in cardiac risk stratification, both for disease assessment and in the identification of patients at risk of plaque rupture. This review summarizes the current knowledge about the role of MPO in CAD with a focus on its possible roles in plaque rupture and recent advances to quantify and image MPO in plasma and atherosclerotic plaques.

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Metabolism of Myeloperoxidase-derived 2-Chlorohexadecanal

Cited by 50 publications

References 50 publications

Identification of glutathione adducts of α-chlorofatty aldehydes produced in activated neutrophils

Identification of glutathione adducts of α-chlorofatty aldehydes produced in activated neutrophils

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

The roles of myeloperoxidase in coronary artery disease and its potential implication in plaque rupture

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