Pleiotropic effects of oxidized phospholipids Bochkov, Valery; Gesslbauer, Bernd; Mauerhofer, Christina ...
Free radical biology & medicine,
October 2017, 2017-Oct, 2017-10-00, 20171001, Volume:
111
Journal Article
Peer reviewed
Open access
Oxidized phospholipids (OxPLs) are increasingly recognized to play a role in a variety of normal and pathological states. OxPLs were implicated in regulation of inflammation, thrombosis, ...angiogenesis, endothelial barrier function, immune tolerance and other important processes. Rapidly accumulating evidence suggests that OxPLs are biomarkers of atherosclerosis and other pathologies. In addition, successful application of experimental drugs based on structural scaffold of OxPLs in animal models of inflammation was recently reported. This review briefly summarizes current knowledge on generation, methods of quantification and biological activities of OxPLs. Furthermore, receptor and cellular mechanisms of these effects are discussed. The goal of the review is to give a broad overview of this class of lipid mediators inducing pleiotropic biological effects.
•Oxidized phospholipids (OxPLs) are increasingly recognized as lipid mediators.•The review summarizes current knowledge on biological effects of OxPLs.•The mechanisms of pleiotropic biological activities of OxPLs are discussed.
In this review paper, the latest literature on the functional properties of phospholipids in relation to inflammation and inflammation-related disorders has been critically appraised and evaluated. ...The paper is divided into three sections:
presents an overview of the relationship between structures and biological activities (pro-inflammatory or anti-inflammatory) of several phospholipids with respect to inflammation.
and
are dedicated to the structures, functions, compositions and anti-inflammatory properties of dietary phospholipids from animal and marine sources. Most of the dietary phospholipids of animal origin come from meat, egg and dairy products. To date, there is very limited work published on meat phospholipids, undoubtedly due to the negative perception that meat consumption is an unhealthy option because of its putative associations with several chronic diseases. These assumptions are addressed with respect to the phospholipid composition of meat products. Recent research trends indicate that dairy phospholipids possess anti-inflammatory properties, which has led to an increased interest into their molecular structures and reputed health benefits. Finally, the structural composition of phospholipids of marine origin is discussed. Extensive research has been published in relation to ω-3 polyunsaturated fatty acids (PUFAs) and inflammation, however this research has recently come under scrutiny and has proved to be unreliable and controversial in terms of the therapeutic effects of ω-3 PUFA, which are generally in the form of triglycerides and esters. Therefore, this review focuses on recent publications concerning marine phospholipids and their structural composition and related health benefits. Finally, the strong nutritional value of dietary phospholipids are highlighted with respect to marine and animal origin and avenues for future research are discussed.
Oxidized phospholipids (OxPL) are ubiquitous, are formed in many inflammatory tissues, including atherosclerotic lesions, and frequently mediate proinflammatory changes
. Because OxPL are mostly the ...products of non-enzymatic lipid peroxidation, mechanisms to specifically neutralize them are unavailable and their roles in vivo are largely unknown. We previously cloned the IgM natural antibody E06, which binds to the phosphocholine headgroup of OxPL, and blocks the uptake of oxidized low-density lipoprotein (OxLDL) by macrophages and inhibits the proinflammatory properties of OxPL
. Here, to determine the role of OxPL in vivo in the context of atherogenesis, we generated transgenic mice in the Ldlr
background that expressed a single-chain variable fragment of E06 (E06-scFv) using the Apoe promoter. E06-scFv was secreted into the plasma from the liver and macrophages, and achieved sufficient plasma levels to inhibit in vivo macrophage uptake of OxLDL and to prevent OxPL-induced inflammatory signalling. Compared to Ldlr
mice, Ldlr
E06-scFv mice had 57-28% less atherosclerosis after 4, 7 and even 12 months of 1% high-cholesterol diet. Echocardiographic and histologic evaluation of the aortic valves demonstrated that E06-scFv ameliorated the development of aortic valve gradients and decreased aortic valve calcification. Both cholesterol accumulation and in vivo uptake of OxLDL were decreased in peritoneal macrophages, and both peritoneal and aortic macrophages had a decreased inflammatory phenotype. Serum amyloid A was decreased by 32%, indicating decreased systemic inflammation, and hepatic steatosis and inflammation were also decreased. Finally, the E06-scFv prolonged life as measured over 15 months. Because the E06-scFv lacks the functional effects of an intact antibody other than the ability to bind OxPL and inhibit OxLDL uptake in macrophages, these data support a major proatherogenic role of OxLDL and demonstrate that OxPL are proinflammatory and proatherogenic, which E06 counteracts in vivo. These studies suggest that therapies inactivating OxPL may be beneficial for reducing generalized inflammation, including the progression of atherosclerosis, aortic stenosis and hepatic steatosis.
Phospholipids are essential components of biological membranes and signal transduction cascades in plants. In recent years, plant phospholipid research was greatly advanced by the characterization of ...numerous mutants affected in phospholipid biosynthesis and the discovery of a number of functionally important phospholipid-binding proteins. It is now accepted that most phospholipids to some extent have regulatory functions, including those that serve as constituents of biological membranes. Phospholipids are more than an inert end product of lipid biosynthesis. This review article summarizes recent advances on phospholipid biosynthesis with a particular focus on polar head group synthesis, followed by a short overview on protein–phospholipid interactions as an emerging regulatory mechanism of phospholipid function in arabidopsis (Arabidopsis thaliana).
In recent years, plant phospholipid research was greatly advanced by the characterization of numerous mutants affected in phospholipid biosynthesis. Now, we have an almost complete version of the phospholipid metabolic map including genes for each reaction step.
In addition to the primary classification of phospholipids according to the structure of the polar head group, the secondary classification based on the hydrophobic acyl tails adds a further level of complexity. This spatiotemporally diverse and dynamic molecular profile of phospholipids determines the physical properties of the membranes, and thus affects the structure and function of each organellar membrane.
An increasing number of lipid-binding proteins reported in recent years have rendered protein–lipid interaction analyses an emerging field of ‘interactome research’ in plant biology.
Some phospholipid molecular species show oscillation in response to diurnal condition. This may create an oscillatory profile of protein–lipid binding and regulate protein functions by the oscillation of interacting phospholipid.
Ethanolamine phosphotransferase (EPT)1, also known as selenoprotein 1 (SELENOI), is an enzyme that transfers phosphoethanolamine from cytidine diphosphate-ethanolamine to lipid acceptors to produce ...ethanolamine glycerophospholipids, such as diacyl-linked phosphatidylethanolamine (PE) and ether-linked plasmalogen 1-alkenyl-2-acyl-glycerophosphoethanolamine (plasmenyl-PE). However, to date there has been no analysis of the metabolomic consequences of the mutation of EPT1 on the concentration of ethanolamine glycerophospholipids in mammalian cells. We studied a patient with severe complicated hereditary spastic paraplegia, sensorineural-deafness, blindness, and seizures. Neuroimaging revealed hypomyelination, followed by brain atrophy mainly in the cerebellum and brainstem. Using whole exome sequencing, we identified a novel EPT1 mutation (exon skipping). In vitro EPT activity, as well as the rate of biosynthesis of ethanolamine glycerophospholipids, was markedly reduced in cultures of the patient's skin fibroblasts. Quantification of phospholipids by LC-MS/MS demonstrated reduced levels of several PE species with polyunsaturated fatty acids, such as 38:6, 38:4, 40:6, 40:5, and 40:4. Notably, most plasmenyl-PE species were significantly decreased in the patient's cells, whereas most plasmanylcholine 1-alkyl-2-acyl-glycerophosphocholine (plasmanyl-PC) species were increased. Similar findings regarding decreased plasmenyl-PE and increased plasmanyl-PC were obtained using EPT1-KO HeLa cells. Our data demonstrate for the first time the indispensable role of EPT1 in the myelination process and neurodevelopment, and in the maintenance of normal homeostasis of ether-linked phospholipids in humans.
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