Ether lipids

Magnusson, Carlos D.; Haraldsson, Guđmundur G.

doi:10.1016/j.chemphyslip.2011.04.010

Cited by 122 publications

(127 citation statements)

References 172 publications

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“…However, some glomerular PC O-38:1 may also be present that could be detected using greater spatial resolution for MALDI-IMS than the 20 m used in this study. Ether-linked PC and PE species differ from the more common diacyl PCs and PEs in their utilization of a fatty alcohol, as opposed to a fatty acid, at the sn1 position (ether vs. ester sn1 linkage) (20). Elevated levels of ether lipids have been widely reported in cancer tissues, and the discovery of important biological activities of distinctive ether-like lipids such as platelet-activating factor (PAF) (9, 37) greatly stimulated interest in these lipids.…”

Section: F1142 Swath and Maldi Imaging Mass Spectrometry Of Lipids Inmentioning

confidence: 99%

Early lipid changes in acute kidney injury using SWATH lipidomics coupled with MALDI tissue imaging

Rao

Walters

Wilson

et al. 2016

American Journal of Physiology-Renal Physiology

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Acute kidney injury (AKI) is one of the leading causes of in-hospital morbidity and mortality, particularly in critically ill patients. Although our understanding of AKI at the molecular level remains limited due to its complex pathophysiology, recent advances in both quantitative and spatial mass spectrometric approaches offer new opportunities to assess the significance of renal metabolomic changes in AKI models. In this study, we evaluated lipid changes in early ischemia-reperfusion (IR)-related AKI in mice by using sequential window acquisition of all theoretical spectra (SWATH)-mass spectrometry (MS) lipidomics. We found a significant increase in two abundant ether-linked phospholipids following IR at 6 h postinjury, a plasmanyl choline, phosphatidylcholine (PC) O-38:1 (O-18:0, 20:1), and a plasmalogen, phosphatidylethanolamine (PE) O-42:3 (O-20:1, 22:2). Both of these lipids correlated with the severity of AKI as measured by plasma creatinine. In addition to many more renal lipid changes associated with more severe AKI, PC O-38:1 elevations were maintained at 24 h post-IR, while renal PE O-42:3 levels decreased, as were all ether PEs detected by SWATH-MS at this later time point. To further assess the significance of this early increase in PC O-38:1, we used matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS) to determine that it occurred in proximal tubules, a region of the kidney that is most prone to IR injury and also rich in the rate-limiting enzymes involved in ether-linked phospholipid biosynthesis. Use of SWATH-MS lipidomics in conjunction with MALDI-IMS for lipid localization will help in elucidating the role of lipids in the pathobiology of AKI.

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Section: F1142 Swath and Maldi Imaging Mass Spectrometry Of Lipids Inmentioning

confidence: 99%

Early lipid changes in acute kidney injury using SWATH lipidomics coupled with MALDI tissue imaging

Rao

Walters

Wilson

et al. 2016

American Journal of Physiology-Renal Physiology

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“…In the experiments, a NIMA (UK) Langmuir trough (total area ¼ 300 cm 2 ) placed on an anti-vibration table was used. Surface pressure was measured (+0.1 mN m…”

Section: Methodsmentioning

confidence: 99%

“…Ether phospholipids comprise a broad family of biologically active compounds, which are very interesting owing to their important functions in living organisms [1,2]. Among this group, a special place belongs to single-chained lipids, which are naturally synthesized as a result of enzymatic activity of phospholipase A2, which hydrolyses the sn-2 bond in the glycerol backbone of a phospholipid molecule [3,4].…”

Section: Introductionmentioning

confidence: 99%

Influence of platelet-activating factor, lyso-platelet-activating factor and edelfosine on Langmuir monolayers imitating plasma membranes of cell lines differing in susceptibility to anti-cancer treatment: the effect of plasmalogen level

Flasiński

Hąc-Wydro

Wydro

et al. 2014

J. R. Soc. Interface.

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ResearchCite this article: Flasiński M, Ha˛c-Wydro K, Wydro P, Dynarowicz-Ła˛tka P. 2014 Influence of platelet-activating factor, lyso-plateletactivating factor and edelfosine on Langmuir monolayers imitating plasma membranes of cell lines differing in susceptibility to anti-cancer treatment: the effect of plasmalogen level. J. R. Soc. Three structurally related but differing in biological activities single-chained ether phospholipids (PAF (platelet-activating factor) and lyso-PAF) and an anti-cancer drug (edelfosine (ED)) were investigated in Langmuir monolayers imitating natural membranes. The aim of the undertaken experiments was to study the influence of these lipids on monolayers mimicking plasma membranes of cell lines differing in susceptibility to the anti-cancer activity of ED, i.e. promyelocytic leukaemia cells (HL-60) and promyeloblastic leukaemia cells (K-562). As these cells differ essentially in the cholesterol/phospholipid ratio and plasmalogen concentration in the membrane, we have carried out systematic investigations in artificial systems of various compositions. The results for model leukaemia cell membrane were compared with data acquired for systems imitating normal leucocytes. Our results show that the level of plasmalogens significantly modulates the influence of the singlechained phospholipids on the investigated systems. The experiments confirmed also that the interactions of ether lipids with a model membrane of HL-60 cells (in biological tests sensitive to ED) have opposite character when compared with K-562, being resistant to ED. Moreover, the values of the parameters characterizing monolayers serving as membrane models (strength of interactions, monolayers fluidity and morphology) proved both sensitivity of these cells to ED and lack of their susceptibility towards PAF. Interestingly, it has been found that lyso-PAF, which is usually described as an inactive precursor of PAF, displays a stronger effect on HL-60 model membranes than ED.

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“…Mammalian lipid droplets also contain ether lipids such as monoalk(en)yldiacylglycerol (MDG) (30). Their precursors may be formed in peroxisomes by the acylation of dihydroxyacetone phosphate and the subsequent exchange of the acyl moiety by a long-chain alcohol to produce the ether linkage present in MDG (43,44), but the enzymes mediating the final conversions, most likely in the ER (45), are still unknown. We show here that Dictyostelium Dgat1 is a good candidate for mediating this reaction (Fig.…”

Section: Subcellular Localization Of Neutral Lipid-producing Enzymesmentioning

confidence: 99%

Dictyostelium discoideum Dgat2 Can Substitute for the Essential Function of Dgat1 in Triglyceride Production but Not in Ether Lipid Synthesis

Herrfurth

Gottlieb

et al. 2014

Eukaryot Cell

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b Triacylglycerol (TAG), the common energy storage molecule, is formed from diacylglycerol and a coenzyme A-activated fatty acid by the action of an acyl coenzyme A:diacylglycerol acyltransferase (DGAT). In order to conduct this step, most organisms rely on more than one enzyme. The two main candidates in Dictyostelium discoideum are Dgat1 and Dgat2. We show, by creating single and double knockout mutants, that the endoplasmic reticulum (ER)-localized Dgat1 enzyme provides the predominant activity, whereas the lipid droplet constituent Dgat2 contributes less activity. This situation may be opposite from what is seen in mammalian cells. Dictyostelium Dgat2 is specialized for the synthesis of TAG, as is the mammalian enzyme. In contrast, mammalian DGAT1 is more promiscuous regarding its substrates, producing diacylglycerol, retinyl esters, and waxes in addition to TAG. The Dictyostelium Dgat1, however, produces TAG, wax esters, and, most interestingly, also neutral ether lipids, which represent a significant constituent of lipid droplets. Ether lipids had also been found in mammalian lipid droplets, but the role of DGAT1 in their synthesis was unknown. The ability to form TAG through either Dgat1 or Dgat2 activity is essential for Dictyostelium to grow on bacteria, its natural food substrate. Fat accumulation is not only a serious health problem in Western societies but also a desired trait in dairy cattle and crop plants. The biochemical pathway of fat synthesis is largely conserved in all organisms and governed by an enzyme activity that performs the last and committed step in fat production, namely, the conversion of diacylglycerol (DAG) to triacylglycerol (TAG) or triglycerides. These so-called acyl coenzyme A (CoA):diacylglycerol acyltransferases (DGATs) are therefore targets for therapeutic drug development and represent objects of intense genetic and biochemical studies (recently reviewed by reference 1).Despite their relevance, the two enzymes mainly responsible for TAG production in mammals, DGAT1 and DGAT2, have been identified only about a decade ago. After the DGAT1 gene was cloned (2) and knocked out (3), the remaining enzyme activity suggested the existence of another enzyme. When the second DGAT was cloned (4), it became obvious that DGAT1 and DGAT2 are divergent in size (roughly 55 versus 43 kDa), differ in the number of transmembrane domains (6 or more versus only 2), and are largely unrelated in sequence (aligned in reference 1).Although both proteins are expressed in virtually all tissues in mammals, their distinguishing features strongly influence their fate in the cell. Whereas DGAT1 is a resident protein of the endoplasmic reticulum (ER) (5), DGAT2 localizes to the ER (6) and to lipid droplets (7). The protein targeting of mammalian DGAT2 to both subcellular locations is even separable by mutations in the primary sequence (8) and thus appears to occur independently.In newborn humans, a homozygous mutation of DGAT1 causes a severe diarrheal disorder that may even be fatal (9). In contrast, tra...

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Ether lipids

Cited by 122 publications

References 172 publications

Early lipid changes in acute kidney injury using SWATH lipidomics coupled with MALDI tissue imaging

Early lipid changes in acute kidney injury using SWATH lipidomics coupled with MALDI tissue imaging

Influence of platelet-activating factor, lyso-platelet-activating factor and edelfosine on Langmuir monolayers imitating plasma membranes of cell lines differing in susceptibility to anti-cancer treatment: the effect of plasmalogen level

Dictyostelium discoideum Dgat2 Can Substitute for the Essential Function of Dgat1 in Triglyceride Production but Not in Ether Lipid Synthesis

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