Search Results (8)

Plasma lipids are essential components of biological systems, transported through interactions with proteins to maintain cellular functions. These lipids exist in various forms, such as fatty acids, glycerolipids, glycerophospholipids, sphingolipids, sterols, and prenol lipids, derived from dietary intake, adipose tissue, and biosynthesis. While the association between certain fatty acids and cardiovascular diseases has been widely recognized, polyunsaturated fatty acids (PUFAs) exhibit cardioprotective effects, reducing risks of arrhythmias and heart-related mortality. This is due to their role in the production of eicosanoids, which modulate inflammation. Chronic inflammation, particularly in obesity, is significantly influenced by fatty acids, with saturated fatty acids promoting inflammation and PUFAs mitigating it. Oxylipins, bioactive molecules derived from the oxidation of PUFAs, play crucial roles in immune regulation across various organisms, including plants, fungi, and bacteria. These molecules, such as prostaglandins, leukotrienes, and resolvins, regulate immune responses during infection and inflammation. The production of oxylipins extends beyond mammals, with fungi and bacteria synthesizing these molecules to modulate immune responses, promoting both defense and pathogenesis. This review delves into the multifaceted effects of oxylipins, exploring their impact on host and microbial interactions, with a focus on their potential for therapeutic applications in modulating infection and immune response. Full article

Plant phytoprostanes (PhytoPs) are lipid oxidative stress mediators that share structural similarities with mammal prostaglandins (PGs). They have been demonstrated to modulate inflammatory processes mediated by prostaglandins. The present study aims to test the effects of the most abundant oxylipin from Gracilaria longissima, ent-9-D1t-Phytoprostane (9-D1t-PhytoP), on platelet activation and vascular cells as well as clarify possible interactions with platelets and the endothelial EP3 receptor Platelet and monocyte activation was assessed by flow cytometry in the presence of purified 9-D1t-PhytoP. Cell migration was studied using the human Ea.hy926 cell line by performing a scratch wound healing assay. The RNA expression of inflammatory markers was evaluated by RT-PCR under inflammatory conditions. Blind docking consensus was applied to the study of the interactions of selected ligands against the EP3 receptor protein. The 9D1t-PhytoP exerts several pharmacological effects; these include prothrombotic and wound-healing properties. In endothelial cells, 9D1t-PhytP mimics the migration stimulus of PGE₂. Computational analysis revealed that 9D1t-PhytP forms a stable complex with the hydrophobic pocket of the EP3 receptor by interaction with the same residues as misoprostol and prostaglandin E₂ (PGE₂), thus supporting its potential as an EP3 agonist. The potential to form procoagulant platelets and the higher endothelial migration rate of the 9-D1t-PhytoP, together with its capability to interact with PGE₂ main target receptor in platelets suggest herein that this oxylipin could be a strong candidate for pharmaceutical research from a multitarget perspective. Full article

Plants perceive pathogenic threats from the environment that have evaded preformed barriers through pattern recognition receptors (PRRs) that recognise microbe-associated molecular patterns (MAMPs). The perception of and triggered defence to lipopolysaccharides (LPSs) as a MAMP is well-studied in mammals, but little is known in plants, including the PRR(s). Understanding LPS-induced secondary metabolites and perturbed metabolic pathways in Arabidopsis will be key to generating disease-resistant plants and improving global plant crop yield. Recently, Arabidopsis LPS-binding protein (LBP) and bactericidal/permeability-increasing protein (BPI)-related proteins (LBP/BPI related-1) and (LBP/BPI related-2) were shown to perceive LPS from Pseudomonas aeruginosa and trigger defence responses. In turn, brassinosteroid insensitive 1 (BRI1)-associated receptor kinase 1 (BAK1) is a well-established co-receptor for several defence-related PRRs in plants. Due to the lack of knowledge pertaining to LPS perception in plants and given the involvement of the afore-mentioned proteins in MAMPs recognition, in this study, Arabidopsis wild type (WT) and mutant (lbr2-2 and bak1-4) plants were pressure-infiltrated with LPSs purified from Pseudomonas syringae pv. tomato DC3000 (Pst) and Xanthomonas campestris pv. campestris 8004 (Xcc). Metabolites were extracted from the leaves at four time points over a 24 h period and analysed by UHPLC-MS, generating distinct metabolite profiles. Data analysed using unsupervised and supervised multivariate data analysis (MVDA) tools generated results that reflected time- and treatment-related variations after both LPS chemotypes treatments. Forty-five significant metabolites were putatively annotated and belong to the following groups: glucosinolates, hydroxycinnamic acid derivatives, flavonoids, lignans, lipids, oxylipins, arabidopsides and phytohormones, while metabolic pathway analysis (MetPA) showed enrichment of flavone and flavanol biosynthesis, phenylpropanoid biosynthesis, alpha-linolenic acid metabolism and glucosinolate biosynthesis. Distinct metabolite accumulations depended on the LPS chemotype and the genetic background of the lbr2-2 and bak1-4 mutants. This study highlights the role of LPSs in the reprogramming Arabidopsis metabolism into a defensive state, and the possible role of LBR and BAK1 proteins in LPSs perception and thus plant defence against pathogenic bacteria. Full article

Algicidal bacteria can lyse microalgal blooms and trigger shifts within plankton communities. Resistant algal species can escape lysis, and have the opportunity to dominate the phytoplankton after a bacterial infection. Despite their important function in ecosystem regulation, little is known about mechanisms of resistance. Here, we show that the diatom Chaetoceros didymus releases eicosanoid oxylipins into the medium, and that the lytic algicidal bacterium, Kordia algicida, induces the production of several wound-activated oxylipins in this resistant diatom. Neither releases nor an induction occurs in the susceptible diatom Skeletonema costatum that is lysed by the bacterium within a few days. Among the upregulated oxylipins, hydroxylated eicosapentaenoic acids (HEPEs) dominate. However, also, resolvins, known lipid mediators in mammals, increase upon exposure of the algae to the algicidal bacteria. The prevailing hydroxylated fatty acid, 15-HEPE, significantly inhibits growth of K. algicida at a concentration of approximately 1 µM. The oxylipin production may represent an independent line of defense of the resistant alga, acting in addition to the previously reported upregulation of proteases. Full article

Structure-activity relationship (SAR) constitutes a crucial topic to discover new bioactive molecules. This approach initiates with the comparison of a target candidate with a molecule or a collection of molecules and their attributed biological functions to shed some light in the details of one or more SARs and subsequently using that information to outline valuable application of the newly identified compounds. Thus, while the empiric knowledge of medicinal chemistry is critical to these tasks, the results retrieved upon dedicated experimental demonstration retrieved resorting to modern high throughput analytical approaches and techniques allow to overwhelm the constraints adduced so far to the successful accomplishment of such tasks. Therefore, the present work reviews critically the evidences reported to date on the occurrence of phytoprostanes and phytofurans in plant foods, and the information available on their bioavailability and biological activity, shedding some light on the expectation waken up due to their structural similarities with prostanoids and isoprostanes. Full article

Oxylipins are well-established lipid mediators in plants and animals. In mammals, arachidonic acid (AA)-derived eicosanoids control inflammation, fever, blood coagulation, pain perception and labor, and, accordingly, are used as drugs, while lipoxygenases (LOX), as well as cyclooxygenases (COX) serve as therapeutic targets for drug development. In soft corals, eicosanoids are synthesized on demand from AA by LOX, COX, and catalase-related allene oxide synthase-lipoxygenase (cAOS-LOX) and hydroperoxide lyase-lipoxygenase (cHPL-LOX) fusion proteins. Reef-building stony corals are used as model organisms for the stress-related genomic studies of corals. Yet, the eicosanoid synthesis capability and AA-derived lipid mediator profiles of stony corals have not been determined. In the current study, the genomic and transcriptomic data about stony coral LOXs, AOS-LOXs, and COXs were analyzed and the eicosanoid profiles and AA metabolites of three stony corals, Acropora millepora, A. cervicornis, and Galaxea fascicularis, were determined by reverse-phase high-performance liquid chromatography (RP-HPLC) coupled with MS-MS and a radiometric detector. Our results confirm that the active LOX and AOS-LOX pathways are present in Acropora sp., which correspond to the genomic/sequence data reported earlier. In addition, LOX, AOS-LOX, and COX products were detected in the closely related species G. fascicularis. In conclusion, the functional 8R-LOX and/or AOS-LOX pathways are abundant among corals, while COXs are restricted to certain soft and stony coral lineages. Full article

Oxylipins are a large and diverse family of fatty acid derivatives exhibiting different levels of oxidation of the carbon chain. They are involved in many biological functions in mammals, plants and diatoms. In this last group of organisms, they are suggested to play a role in the reproductive failure of copepod predators, showing clear pro-apoptotic effects on newborn nauplii. In this work, these compounds were tested for the ability to induce mitotic arrest in sea urchin embryos. We show for the first time that oxylipins have an increased efficacy in their corresponding methylated form. Natural oxylipins were also used as an inspiration for the rational design and synthesis of stable chemical analogs with apoptotic activity against tumor cell lines. This approach led to the synthesis of the linear C15-ketol (22) that was shown to induce apoptosis in human leukemia U-937 cells. These results are proof of the concept of the use of eco-physiological considerations as a platform to guide the search for novel drug candidates. Full article

Oxylipins regulate Aspergillus development and mycotoxin production and are also involved in Aspergillus quorum sensing mechanisms. Despite extensive knowledge of how these oxylipins are synthesized and what processes they regulate, nothing is known about how these signals are detected and transmitted by the fungus. G protein-coupled receptors (GPCR) have been speculated to be involved as they are known oxylipin receptors in mammals, and many putative GPCRs have been identified in the Aspergilli. Here, we present evidence that oxylipins stimulate a burst in cAMP in A. nidulans, and that loss of an A. nidulans GPCR, gprD, prevents this cAMP accumulation. A. flavus undergoes an oxylipin-mediated developmental shift when grown at different densities, and this regulates spore, sclerotial and aflatoxin production. A. flavus encodes two putative GprD homologs, GprC and GprD, and we demonstrate here that they are required to transition to a high-density development state, as well as to respond to spent medium of a high-density culture. The finding of GPCRs that regulate production of survival structures (sclerotia), inoculum (spores) and aflatoxin holds promise for future development of anti-fungal therapeutics. Full article