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Scientific Reports Jan 2021Throughout infection, plant-parasitic nematodes activate a complex host defense response that will regulate their development and aggressiveness. Oxylipins-lipophilic...
Throughout infection, plant-parasitic nematodes activate a complex host defense response that will regulate their development and aggressiveness. Oxylipins-lipophilic signaling molecules-are part of this complex, performing a fundamental role in regulating plant development and immunity. At the same time, the sedentary root-knot nematode Meloidogyne spp. secretes numerous effectors that play key roles during invasion and migration, supporting construction and maintenance of nematodes' feeding sites. Herein, comprehensive oxylipin profiling of tomato roots, performed using LC-MS/MS, indicated strong and early responses of many oxylipins following root-knot nematode infection. To identify genes that might respond to the lipidomic defense pathway mediated through oxylipins, RNA-Seq was performed by exposing Meloidogyne javanica second-stage juveniles to tomato protoplasts and the oxylipin 9-HOT, one of the early-induced oxylipins in tomato roots upon nematode infection. A total of 7512 differentially expressed genes were identified. To target putative effectors, we sought differentially expressed genes carrying a predicted secretion signal peptide. Among these, several were homologous with known effectors in other nematode species; other unknown, potentially secreted proteins may have a role as root-knot nematode effectors that are induced by plant lipid signals. These include effectors associated with distortion of the plant immune response or manipulating signal transduction mediated by lipid signals. Other effectors are implicated in cell wall degradation or ROS detoxification at the plant-nematode interface. Being an integral part of the plant's defense response, oxylipins might be placed as important signaling molecules underlying nematode parasitism.
Topics: Animals; Cell Communication; Host-Parasite Interactions; Solanum lycopersicum; Oxylipins; Signal Transduction; Tylenchoidea
PubMed: 33431951
DOI: 10.1038/s41598-020-79432-6 -
Physiological Reports Jun 2020Chronic kidney disease (CKD) is an important risk factor for cardiovascular and all-cause mortality. Survival rates among end-stage renal disease (ESRD) hemodialysis...
Chronic kidney disease (CKD) is an important risk factor for cardiovascular and all-cause mortality. Survival rates among end-stage renal disease (ESRD) hemodialysis patients are poor and most deaths are related to cardiovascular disease. Oxylipins constitute a family of oxygenated natural products, formed from fatty acid by pathways involving at least one step of dioxygen-dependent oxidation. They are derived from polyunsaturated fatty acids (PUFAs) by cyclooxygenase (COX) enzymes, by lipoxygenases (LOX) enzymes, or by cytochrome P450 epoxygenase. Oxylipins have physiological significance and some could be of regulatory importance. The effects of decreased renal function and dialysis treatment on oxylipin metabolism are unknown. We studied 15 healthy persons and 15 CKD patients undergoing regular hemodialysis treatments and measured oxylipins (HPLC-MS lipidomics) derived from cytochrome P450 (CYP) monooxygenase and lipoxygenase (LOX)/CYP ω/(ω-1)-hydroxylase pathways in circulating blood. We found that all four subclasses of CYP epoxy metabolites were increased after the dialysis treatment. Rather than resulting from altered soluble epoxide hydrolase (sEH) activity, the oxylipins were released and accumulated in the circulation. Furthermore, hemodialysis did not change the majority of LOX/CYP ω/(ω-1)-hydroxylase metabolites. Our data support the idea that oxylipin profiles discriminate ESRD patients from normal controls and are influenced by renal replacement therapies.
Topics: Case-Control Studies; Female; Humans; Lipidomics; Male; Middle Aged; Oxylipins; Renal Dialysis; Renal Insufficiency, Chronic
PubMed: 32562348
DOI: 10.14814/phy2.14447 -
New bioactive oxylipins formed by non-enzymatic free-radical-catalyzed pathways: the phytoprostanes.Lipids Oct 2009In animals and plants, fatty acids with at least three double bonds can be oxidized to prostaglandin-like compounds via enzymatic and non-enzymatic pathways. The most... (Review)
Review
In animals and plants, fatty acids with at least three double bonds can be oxidized to prostaglandin-like compounds via enzymatic and non-enzymatic pathways. The most common fatty acid precursor in mammals is arachidonic acid (C20:4) (AA) which can be converted through the cyclooxygenase pathway to a series of prostaglandins (PG). Non-enzymatic cyclization of arachidonate yields a series of isoprostanes (IsoP) which comprises all PG (minor compounds) as well as PG isomers that cannot be formed enzymatically. In contrast, in plants, alpha-linolenic acid (C18:3) (ALA) is the most common substrate for the allene oxide synthase pathway leading to the jasmonate (JA) family of lipid mediators. Non-enzymatic oxidation of linolenate leads to a series of C18-IsoPs termed dinor IsoP or phytoprostanes (PP). PP structurally resemble JA but cannot be formed enzymatically. We will give an overview of the biological activity of the different classes of PP and also discuss their analytical applications and the strategies developed so far for the total synthesis of PP, depending on the synthetic approaches according to the targets and which key steps serve to access the natural products.
Topics: Animals; Catalysis; Cyclopentanes; Fatty Acids, Unsaturated; Free Radicals; Humans; Isoprostanes; Oxylipins; Signal Transduction
PubMed: 19789901
DOI: 10.1007/s11745-009-3351-1 -
Molecules (Basel, Switzerland) May 2023Wheat is critical for food security, and is challenged by biotic stresses, chiefly aphids and the viruses they transmit. The objective of this study was to determine...
Wheat is critical for food security, and is challenged by biotic stresses, chiefly aphids and the viruses they transmit. The objective of this study was to determine whether aphids feeding on wheat could trigger a defensive plant reaction to oxidative stress that involved plant oxylipins. Plants were grown in chambers with a factorial combination of two nitrogen rates (100% N vs. 20% N in Hoagland solution), and two concentrations of CO (400 vs. 700 ppm). The seedlings were challenged with or for 8 h. Wheat leaves produced phytoprostanes (PhytoPs) of the F series, and three types of phytofurans (PhytoFs): -16()-13--ST-Δ-9-PhytoF, -16()-9--ST-Δ-10-PhytoF and -9()-12--ST-Δ-13-PhytoF. The oxylipin levels varied with aphids, but not with other experimental sources of variation. Both and reduced the concentrations of -16()-13--ST-Δ-9-PhytoF and -16()-9--ST-Δ-10-PhytoF in relation to controls, but had little or no effect on PhytoPs. Our results are consistent with aphids affecting the levels of PUFAs (oxylipin precursors), which decreased the levels of PhytoFs in wheat leaves. Therefore, PhytoFs could be postulated as an early indicator of aphid hosting for this plant species. This is the first report on the quantification of non-enzymatic PhytoFs and PhytoPs in wheat leaves in response to aphids.
Topics: Animals; Oxylipins; Aphids; Triticum; Carbon Dioxide; Plant Leaves
PubMed: 37241874
DOI: 10.3390/molecules28104133 -
The FEBS Journal Sep 2009One of the most challenging questions in modern plant science is how plants regulate their morphological and developmental adaptation in response to changes in their... (Review)
Review
One of the most challenging questions in modern plant science is how plants regulate their morphological and developmental adaptation in response to changes in their biotic and abiotic environment. A comprehensive elucidation of the underlying mechanisms will help shed light on the extremely efficient strategies of plants in terms of survival and propagation. In recent years, a number of environmental stress conditions have been described as being mediated by signaling molecules of the oxylipin family. In this context, jasmonic acid, its biosynthetic precursor, 12-oxo-phytodienoic acid (OPDA), and also reactive electrophilic species such as phytoprostanes play pivotal roles. Although our understanding of jasmonic acid-dependent processes and jasmonic acid signal-transduction cascades has made considerable progress in recent years, knowledge of the regulation and mode of action of OPDA-dependent plant responses is just emerging. This minireview focuses on recent work concerned with the elucidation of OPDA-specific processes in plants. In this context, aspects such as the differential recruitment of OPDA, either by de novo biosynthesis or by release from cyclo-oxylipin-galactolipids, and the conjugation of free OPDA are discussed.
Topics: Cyclopentanes; Fatty Acids, Unsaturated; Galactolipids; Oxylipins; Plants; Signal Transduction
PubMed: 19663904
DOI: 10.1111/j.1742-4658.2009.07195.x -
Food & Function Jul 2017A growing body of evidence suggests that the intake of the long chain omega-3 polyunsaturated fatty acids (n3-PUFA) eicosapentaenoic acid (C20:5 n3, EPA) and... (Review)
Review
A growing body of evidence suggests that the intake of the long chain omega-3 polyunsaturated fatty acids (n3-PUFA) eicosapentaenoic acid (C20:5 n3, EPA) and docosahexaenoic acid (C22:6 n3, DHA) is linked to beneficial health effects, particularly in the prevention of cardiovascular and inflammatory diseases. Although the molecular mode of action of n3-PUFA is still not fully understood, it is not controversial that a significant portion of the (patho)-physiological effects of PUFA are mediated by their oxidative metabolites, i.e. eicosanoids and other oxylipins. Quantitative targeted oxylipin methods allow the comprehensive monitoring of n3-PUFA supplementation induced changes in the pattern of oxylipins in order to understand their biology. In this short review, results from intervention studies are summarized analyzing >30 oxylipins from different PUFAs in response to n3-PUFA supplementation. The results are not only qualitatively compared with respect to the study design, n3-PUFA dose and trends in the lipid mediators, but also quantitatively based on the relative change in the oxylipin level induced by n3-PUFA. The evaluation of the data from the studies shows that the change in oxylipins generally corresponded to the observed changes in their precursor PUFA, i.e. the lower the individual n3-status at the baseline, the higher the increase in EPA and DHA derived oxylipins. The strongest relative increases were found for EPA derived oxylipins, while changes in arachidonic acid (C20:4 n6, ARA) derived eicosanoids were heterogeneous. After 3-12 weeks of supplementation, similar relative changes were observed in free and total (free + esterified) oxylipins in plasma and serum. Regarding EPA derived oxylipins, the results indicate a trend for a linear increase with dose. However, the interpretation of the quantitative oxylipin patterns between studies is hampered by strong inter-individual variances in oxylipin levels between and also within the studies. In the future, the reason for these varying oxylipin plasma concentrations needs to be clarified in order to understand oxylipin and n3-PUFA biology.
Topics: Animals; Dietary Supplements; Fatty Acids; Fatty Acids, Omega-3; Humans; Oxylipins
PubMed: 28682409
DOI: 10.1039/c7fo00403f -
Digestive Diseases and Sciences Dec 2020Activation of innate immunity by gut-derived immunogens such as lipopolysaccharides (LPS) may play an important role in the pathogenesis of nonalcoholic fatty liver...
BACKGROUND
Activation of innate immunity by gut-derived immunogens such as lipopolysaccharides (LPS) may play an important role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Whether NAFLD-associated lipid disturbances and polyunsaturated fatty acid (PUFA) metabolism in particular contribute to heightened innate immunity, remains to be determined.
OBJECTIVE
To determine if oxylipins, metabolic products of PUFA metabolism, enhance innate immune reactivity alone and/or following exposure to LPS.
METHODS
Plasma and peripheral blood mononuclear cells (PBMC) were collected from 35 NAFLD patients and 8 healthy controls. Oxylipin levels were documented by HPLC-MS/MS, cytokines (IL-1, IL-6, IL-10, and TNF-α) by ELISA, and chemokine receptors (CCR1 and CCR2) by flow cytometry.
RESULTS
Mean plasma levels of four pro-inflammatory oxylipins (Tetranor 12-HETE, 20-HETE, 8-HETrE, and 7-HDoHE) were significantly elevated in NAFLD patients compared to healthy controls. However, the levels did not correlate with the severity of liver injury as reflected by serum aminotransferases, ck18M30, and Fib-4 determinations. In vitro, 20-HETE (0.01-100 nM), the plasma oxylipin with the most significantly elevated plasma levels, did not alter NAFLD or control PBMC cytokine release or enhance the increases in cytokine release following 24 h of LPS exposure. Similarly, 20-HETE alone did not alter PBMC CCR1 or CCR2 expression or LPS-induced downregulation of these receptors.
CONCLUSIONS
Pro-inflammatory oxylipin levels are increased in NAFLD, but these metabolites do not appear to drive short-term direct or LPS-induced increases in PBMC cytokine release or chemotaxis.
Topics: Correlation of Data; Cytokines; Female; Humans; Leukocytes, Mononuclear; Liver; Liver Function Tests; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Oxylipins; Receptors, Chemokine; Severity of Illness Index
PubMed: 31997053
DOI: 10.1007/s10620-020-06095-8 -
Cell Metabolism Jun 2021Cellular senescence is a stress or damage response that causes a permanent proliferative arrest and secretion of numerous factors with potent biological activities. This...
Cellular senescence is a stress or damage response that causes a permanent proliferative arrest and secretion of numerous factors with potent biological activities. This senescence-associated secretory phenotype (SASP) has been characterized largely for secreted proteins that participate in embryogenesis, wound healing, inflammation, and many age-related pathologies. By contrast, lipid components of the SASP are understudied. We show that senescent cells activate the biosynthesis of several oxylipins that promote segments of the SASP and reinforce the proliferative arrest. Notably, senescent cells synthesize and accumulate an unstudied intracellular prostaglandin, 1a,1b-dihomo-15-deoxy-delta-12,14-prostaglandin J2. Released 15-deoxy-delta-12,14-prostaglandin J2 is a biomarker of senolysis in culture and in vivo. This and other prostaglandin D2-related lipids promote the senescence arrest and SASP by activating RAS signaling. These data identify an important aspect of cellular senescence and a method to detect senolysis.
Topics: Animals; Biomarkers; Cell Line; Humans; Mice; Mice, Inbred C57BL; Oxylipins; Senescence-Associated Secretory Phenotype; Senotherapeutics
PubMed: 33811820
DOI: 10.1016/j.cmet.2021.03.008 -
Current Atherosclerosis Reports Nov 2009Eicosanoids, including epoxyeicosatrienoic acids, hydroxyeicosatetraenoic acids, and other oxylipins derived from polyunsaturated fatty acids, have emerging roles in... (Review)
Review
Eicosanoids, including epoxyeicosatrienoic acids, hydroxyeicosatetraenoic acids, and other oxylipins derived from polyunsaturated fatty acids, have emerging roles in endothelial inflammation and subsequent atherosclerosis. Unlike eicosanoids in the prostanoid series, they are known to be esterified in cell lipids such as phospholipids and triglycerides; however, our understanding of these reservoirs is in its infancy. This review focuses on recent work identifying circulating oxylipins, primarily esterified with lipoprotein lipids, and their effects on markers of endothelial dysfunction. These oxylipins are known to be released by at least one lipase (lipoprotein lipase) and to mediate increased expression of inflammatory markers in endothelial cells, which coincides with the known roles of lipoproteins in endothelial dysfunction. The implications of the lipolytic release of lipoprotein-bound oxylipins for the inflammatory response, challenges to analysis of this oxylipin compartment, and the potential importance of non-arachidonate-derived oxylipins are discussed.
Topics: Atherosclerosis; Eicosanoids; Endothelium, Vascular; Humans; Inflammation; Oxylipins
PubMed: 19852880
DOI: 10.1007/s11883-009-0061-3 -
Phytochemistry Sep 2009Oxidized lipids in plants comprise a variety of reactive electrophiles that contain an alpha,beta-unsaturated carbonyl group. While some of these compounds are formed... (Review)
Review
Oxidized lipids in plants comprise a variety of reactive electrophiles that contain an alpha,beta-unsaturated carbonyl group. While some of these compounds are formed enzymatically, many of them are formed by non-enzymatic pathways. In addition to their chemical reactivity/toxicity low levels of these compounds are also biologically active. Despite their structural diversity and biosynthetic origin, common biological activities such as induction of defense genes, activation of detoxification responses and growth inhibition have been documented. However, reactive electrophilic oxylipins are poorly defined as a class of compounds but have at least two properties in common, i.e., lipophilicity and thiol-reactivity. Thiol-reactivity is a property of reactive oxylipins (RES) shared by reactive oxygen and nitrogen species (ROS and RNS) and enables these agents to modify proteins in vivo. Thiol-modification is assumed to represent a key mechanism involved in signal transduction. A metaanalysis of proteomic studies reveals that RES oxylipins, ROS and RNS apparently chemically modify a similar set of highly sensitive proteins, virtually all of which are targets for thioredoxins. Moreover, most of these proteins are redox-regulated, i.e., posttranslational thiol-modification alters the activity or function of these proteins. On the transcriptome level, effects of RES oxylipins and ROS on gene induction substantially overlap but are clearly different. Besides electrophilicity other structural properties such as target affinity apparently determine target selectivity and biological activity. In this context, different signalling mechanisms and signal transduction components identified in plants and non-plant organisms as well as putative functions of RES oxylipins are discussed.
Topics: Gene Expression Regulation, Plant; Molecular Structure; Oxidation-Reduction; Oxylipins; Reactive Oxygen Species; Signal Transduction
PubMed: 19555983
DOI: 10.1016/j.phytochem.2009.05.018