The chlorinated lipidome originating from myeloperoxidase-derived HOCl targeting plasmalogens: Metabolism, clearance, and biological properties

Palladino, Elisa N.D.; Hartman, Celine L.; Albert, Carolyn J.; Ford, David A.

doi:10.1016/j.abb.2018.01.010

Cited by 24 publications

(13 citation statements)

References 87 publications

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“…EVs derived from IECs have been demonstrated to be necessary for tolerogenic [82]. The MPO function is to induce the oxidation reaction by producing reactive oxidants, such as hypohalous acids [83][84][85]. The increased level of oxidative stress can withstand the microbes in the gut of patients with IBD [86].…”

Section: Evs Derived From Iec Regulation Of Gut Immunementioning

confidence: 99%

Extracellular Vesicles with Possible Roles in Gut Intestinal Tract Homeostasis and IBD

Chang

Wang

Zhao

et al. 2020

Mediators of Inflammation

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The intestinal tract consists of various types of cells, such as epithelial cells, Paneth cells, macrophages, and lymphocytes, which constitute the intestinal immune system and play a significant role in maintaining intestinal homeostasis by producing antimicrobial materials and controlling the host-commensal balance. Various studies have found that the dysfunction of intestinal homeostasis contributes to the pathogenesis of inflammatory bowel disease (IBD). As a novel mediator, extracellular vesicles (EVs) have been recognized as effective communicators, not only between cells but also between cells and the organism. In recent years, EVs have been regarded as vital characters for dysregulated homeostasis and IBD in either the etiology or the pathology of intestinal inflammation. Here, we review recent studies on EVs associated with intestinal homeostasis and IBD and discuss their source, cargo, and origin, as well as their therapeutic effects on IBD, which mainly include artificial nanoparticles and EVs derived from microorganisms.

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Section: Evs Derived From Iec Regulation Of Gut Immunementioning

confidence: 99%

Extracellular Vesicles with Possible Roles in Gut Intestinal Tract Homeostasis and IBD

Chang

Wang

Zhao

et al. 2020

Mediators of Inflammation

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“…Chronic activation of phagocytes results in elevated levels of HOCl that can modify a wide range of biomolecules including antioxidants, nucleotides, DNA, (lipo)proteins, and lipids. Thus, prolonged production of HOCl causes tissue injury [17,18] and leads to the formation of a chlorinated lipidome with deleterious functions [18]. In addition to modification of ether-phospholipid plasmalogens [18], HOCl is able to modify SL [19] with a second order rate constant in the range observed for plasmalogens [20].…”

Section: Introductionmentioning

confidence: 99%

Myeloperoxidase and Septic Conditions Disrupt Sphingolipid Homeostasis in Murine Brain Capillaries In Vivo and Immortalized Human Brain Endothelial Cells In Vitro

Goeritzer

Bernhart

Plastira

et al. 2020

IJMS

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During inflammation, activated leukocytes release cytotoxic mediators that compromise blood–brain barrier (BBB) function. Under inflammatory conditions, myeloperoxidase (MPO) is critically involved in inflicting BBB damage. We used genetic and pharmacological approaches to investigate whether MPO induces aberrant lipid homeostasis at the BBB in a murine endotoxemia model. To corroborate findings in a human system we studied the impact of sera from sepsis and non-sepsis patients on brain endothelial cells (hCMEC/D3). In response to endotoxin, the fatty acid, ceramide, and sphingomyelin content of isolated mouse brain capillaries dropped and barrier dysfunction occurred. In mice, genetic deficiency or pharmacological inhibition of MPO abolished these alterations. Studies in metabolic cages revealed increased physical activity and less pronounced sickness behavior of MPO−/− compared to wild-type mice in response to sepsis. In hCMEC/D3 cells, exogenous tumor necrosis factor α (TNFα) potently regulated gene expression of pro-inflammatory cytokines and a set of genes involved in sphingolipid (SL) homeostasis. Notably, treatment of hCMEC/D3 cells with sera from septic patients reduced cellular ceramide concentrations and induced barrier and mitochondrial dysfunction. In summary, our in vivo and in vitro data revealed that inflammatory mediators including MPO, TNFα induce dysfunctional SL homeostasis in brain endothelial cells. Genetic and pharmacological inhibition of MPO attenuated endotoxin-induced alterations in SL homeostasis in vivo, highlighting the potential role of MPO as drug target to treat inflammation-induced brain dysfunction.

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“…These have altered biological properties and can be considered as biological mediators. In contrast, vinyl ether bonds are susceptible to attack by radicals ( 23 ) and electrophilic oxidants ( 24 ), forming oxidant-dependent products. Phospholipid headgroups containing an amine group can also undergo oxidation, although the quaternary ammonium structure of phosphocholine is resistant; changes in headgroup structure are likely to impact significantly on the phospholipid function within the cell membrane ( 25 , 26 ).…”

Section: Chemical Properties Of Lipids That Enable Modificationsmentioning

confidence: 99%

Formation of Oxidatively Modified Lipids as the Basis for a Cellular Epilipidome

Spickett

2020

Front. Endocrinol.

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While often regarded as a subset of metabolomics, lipidomics can better be considered as a field in its own right. While the total number of lipid species in biology may not exceed the number of metabolites, they can be modified chemically and biochemically leading to an enormous diversity of derivatives, many of which retain the lipophilic properties of lipids and thus expand the lipidome greatly. Oxidative modification by radical oxygen species, either enzymatically or chemically, is one of the major mechanisms involved, although attack by non-radical oxidants also occurs. The modified lipids typically contain more oxygens in the form of hydroxyl, epoxide, carbonyl and carboxylic acid groups, and nitration, nitrosylation, halogenation or sulfation can also occur. This article provides a succinct overview of the types of species formed, the reactive compounds involved and the specific molecular sites that they react with, and the biochemical or chemical mechanisms involved. In many cases, these modifications reduce the stability of the lipid, and breakdown products are formed, which themselves have interesting properties such as the ability to react with other biomolecules. Publications on the biological effects of modified lipids are growing rapidly, supporting the concept that some of these biomolecules have potential signaling and regulatory effects. The question therefore arises whether modified lipids represent an “epilipidome”, analogous to the epigenetic modifications that can control gene expression.

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The chlorinated lipidome originating from myeloperoxidase-derived HOCl targeting plasmalogens: Metabolism, clearance, and biological properties

Cited by 24 publications

References 87 publications

Extracellular Vesicles with Possible Roles in Gut Intestinal Tract Homeostasis and IBD

Extracellular Vesicles with Possible Roles in Gut Intestinal Tract Homeostasis and IBD

Myeloperoxidase and Septic Conditions Disrupt Sphingolipid Homeostasis in Murine Brain Capillaries In Vivo and Immortalized Human Brain Endothelial Cells In Vitro

Formation of Oxidatively Modified Lipids as the Basis for a Cellular Epilipidome

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