Sphingolipids of plant pathogenic fungi

Glycosphingolipids in filamentous fungi are significant components of the plasma membrane and are vital for different cellular processes, such as growth, morphological transition or signal transduction. Fungal growth inhibitors targeting glycosylinositolphosphoceramide (GIPCs) biosynthesis or antifungal compounds binding to GIPCs present in membranes could present a safe way of preventing fungal growth on crops since GIPCs are not present in mammalian cells. Mass spectrometry-based shotgun lipidomics was used to analyze sphingolipids of 11 fungal strains isolated from plant material. Molecular species with inositol ceramides containing zero to five carbohydrates were identified. Differences in the amount of individual molecular species were influenced by the taxonomic affiliation. All tested strains exhibited a relatively high content (more than 40 mol.%) of GIPCs with three and more saccharides attached to the polar head. It could be assumed that the sphingolipid profiles of the tested plant pathogens would be an adaptation mechanism to antifungal plant defensins.

Redox Epiphospholipidome in Programmed Cell Death Signaling: Catalytic Mechanisms and Regulation

A huge diversification of phospholipids, forming the aqueous interfaces of all biomembranes, cannot be accommodated within a simple concept of their role as membrane building blocks. Indeed, a number of signaling functions of (phospho)lipid molecules has been discovered. Among these signaling lipids, a particular group of oxygenated polyunsaturated fatty acids (PUFA), so called lipid mediators, has been thoroughly investigated over several decades. This group includes oxygenated octadecanoids, eicosanoids, and docosanoids and includes several hundreds of individual species. Oxygenation of PUFA can occur when they are esterified into major classes of phospholipids. Initially, these events have been associated with non-specific oxidative injury of biomembranes. An alternative concept is that these post-synthetically oxidatively modified phospholipids and their adducts with proteins are a part of a redox epiphospholipidome that represents a rich and versatile language for intra- and inter-cellular communications. The redox epiphospholipidome may include hundreds of thousands of individual molecular species acting as meaningful biological signals. This review describes the signaling role of oxygenated phospholipids in programs of regulated cell death. Although phospholipid peroxidation has been associated with almost all known cell death programs, we chose to discuss enzymatic pathways activated during apoptosis and ferroptosis and leading to peroxidation of two phospholipid classes, cardiolipins (CLs) and phosphatidylethanolamines (PEs). This is based on the available LC-MS identification and quantitative information on the respective peroxidation products of CLs and PEs. We focused on molecular mechanisms through which two proteins, a mitochondrial hemoprotein cytochrome c (cyt c), and non-heme Fe lipoxygenase (LOX), change their catalytic properties to fulfill new functions of generating oxygenated CL and PE species. Given the high selectivity and specificity of CL and PE peroxidation we argue that enzymatic reactions catalyzed by cyt c/CL complexes and 15-lipoxygenase/phosphatidylethanolamine binding protein 1 (15LOX/PEBP1) complexes dominate, at least during the initiation stage of peroxidation, in apoptosis and ferroptosis. We contrast cell-autonomous nature of CLox signaling in apoptosis correlating with its anti-inflammatory functions vs. non-cell-autonomous ferroptotic signaling facilitating pro-inflammatory (necro-inflammatory) responses. Finally, we propose that small molecule mechanism-based regulators of enzymatic phospholipid peroxidation may lead to highly specific anti-apoptotic and anti-ferroptotic therapeutic modalities.

Levels of phospholipids and triacylglycerol-containing omega 3 fatty acids in myocardial tissue of patients with myocardial infarction: analyzed by a lipidomics profiling method

Objective According to population-based studies, low omega 3 fatty acid (omega3FA) intake and high levels of serum triacylglycerol (TAG) are associated with cardiovascular diseases. Recent advances in mass spectrometry allow molecular lipid (lipidomics) profiling, which may enhance cardiovascular risk prediction. In this study, we assessed the levels of omega3FA-containing phospholipids (PL) and TAG in myocardial tissues of patients with and without myocardial infarction (MI) using a lipidomics profiling method. Methods We performed lipidomics profiling of human left atrial appendage (LAA) tissue of 29 consecutive patients receiving off-pump coronary bypass surgery with standard LAA resection. The patients were divided into the MI group (n=7) and an age- and gender-matched non-MI group (n=7). Results Lipidomics profiling revealed that the MI group tended to have low levels of phosphatidylcholines (PC), phosphatidylethanolamine (PE), lysophosphatidylethanolamine (LPE), and plasmalogen, and high levels of TAG species. Individual molecular species containing omega3FA, such as PC (18:0/20:5; 3,200±1,200 vs. 4,500±910 pmol/g tissue, p=0.04) and plasmalogen (18:1/20:5; 57,000±21,000 vs. 91,000±28,000 pmol/g tissue, p=0.02), were significantly lower in the MI group than in the non-MI group. Conclusions To our knowledge, this is the first study to determine the levels of omega3FA-containing PL and TAG in myocardial tissue using lipidomics profiling. We discovered that lower levels of omega3FA-containing PL and higher levels of TAG existed in myocardial tissues of patients with MI than in those of patients without MI. Accordingly, the lipidomics profiling method for human myocardial tissue may be useful for developing therapy targets for cardiovascular diseases. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): MEXT/JSPS KAKENHI Grant

Anti-Inflammatory Properties of Plant Derived Natural Products – A Systematic Review

Traditionally, natural medicines have been administered as plant extracts, which are composed of a mixture of molecules. The individual molecular species in this mixture may or may not contribute to the overall medicinal effects and some may even oppose the beneficial activity of others. To better control therapeutic effects, studies that characterized specific molecules and describe their individual activity that have been performed over the past decades. These studies appear to underline that natural products are particularly effective as antioxidants and anti-inflammatory agents. In this systematic review we aimed to identify potent anti-inflammatory natural products and relate their efficacy to their chemical structure and physicochemical properties. To identify these compounds, we performed a comprehensive literature search to find those studies, in which a dose-response description and a positive control reference compound was used to benchmark the observed activity. Of the analyzed papers, 7% of initially selected studies met these requirements and were subjected to further analysis. This analysis revealed that most selected natural products indeed appeared to possess anti-inflammatory activities, in particular anti-oxidative properties. In addition, 14% of the natural products outperformed the remaining natural products in all tested assays and are attractive candidates as new anti-inflammatory agents.

Relationship between the lipid composition of maternal plasma and infant plasma through breast milk

Introduction This study was motivated by the report that infant development correlates with particular lipids in infant plasma. Objective The hypothesis was that the abundance of these candidate biomarkers is influenced by the dietary intake of the infant. Methods A cohort of 30 exclusively-breastfeeding mother–infant pairs from a small region of West Africa was used for this observational study. Plasma and milk from the mother and plasma from her infant were collected within 24 h, 3 months post partum. The lipid, sterol and glyceride composition was surveyed using direct infusion MS in positive and negative ion modes. Analysis employed a combination of univariate and multivariate tests. Results The lipid profiles of mother and infant plasma samples are similar but distinguishable, and both are distinct from milk. Phosphatidylcholines (PC), cholesteryl esters (CEs) and cholesterol were more abundant in mothers with respect to their infants, e.g. PC(34:1) was 5.66% in mothers but 3.61% in infants (p = 3.60 × 10−10), CE(18:2) was 8.05% in mothers but 5.18% in infants (p = 1.37 × 10−11) whilst TGs were lower in mothers with respect to their infants, e.g. TG(52:2) was 2.74% in mothers and 4.23% in infants (p = 1.63 × 10−05). A latent structure model showed that four lipids in infant plasma previously shown to be biomarkers clustered with cholesteryl esters in the maternal circulation. Conclusion This study found evidence that the abundance of individual lipid isoforms associated with infant development are associated with the abundance of individual molecular species in the mother’s circulation.

Lipid Isolation Process and Study on Some Molecular Species of Polar Lipid Isolated from Seed of Madhuca ellitica

This study attempted the lipid extraction process from the seeds of Madhuca ellitica, a lipid-rich plant, and conducted a lipidomic analysis on molecular species of the obtained product. Total lipids of the crude seeds were found to contain 11.2% of polar lipids. The major fatty acids (FAs) of the polar lipids were palmitic (16:0), stearic (18:0), oleic (18:1n-9), and linoleic (18:2n-6) acids, which amounted to 28.5, 12.5, 44.8, and 13.2% of total FAs, respectively. The content and chemical structures of individual molecular species of phosphatidylglycerol (PG), phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylinositol (PI), phosphatidic acid (PA), and sulfoquinovosyldiacylglycerol (SQDG) were determined by HPLC with a tandem high-resolution mass spectrometry (HRMS). The major molecular species were 18:1/18:2 PE, 16:0/18:1 PC, 18:1/18:2 PC, 16:0/18:2 PG, 16:0/18:1 PG, 16:1/18:1 PI, 16:0/18:1 PI, 18:0/18:2 PI, 16:0/18:1 PA, 18:1/18:2 PA, 16:0/18:1 SQDG, and 18:0/18:1 SQDG. The application of a tandem HRMS allows us to determine the content of each isomer in pairs of the monoisotopic molecular species, for example, 18:0/18:2 and 18:1/18:1. The evaluation of the seed polar lipid profile will be helpful for developing the potential of this tree for nutritive and industrial uses.

Condensation Reactions Synthesize Random Polymers

Over the past half century of serious research on the origin of life, several schools of thought have emerged that focus on “worlds” and what came first in the pathway to the origin of life. One example is the RNA World, a term coined by Walter Gilbert after the discovery of ribozymes. Other examples include the Iron-Sulfur World of Günther Wächtershäuser and the Lipid World proposed by Doron Lancet and coworkers. Then we have a competition between “metabolism first” and “replication first” schools. The worlds and schools have the positive effect of sharpening arguments and forcing us to think carefully, but they also can lock researchers into defending their individual approaches rather than looking for patterns in a larger perspective. One of the main themes of this book is the notion that the first living cells were systems of functional polymers working together within membranous compartments. Therefore, it is best not to think of “worlds” and “firsts” as fundamentals but instead as components evolving together toward the assembly of an encapsulated system of functional polymers. At first the polymers will be composed of random sequences of their monomers, and the compartments will contain random assortments of polymers. Here, we refer to these structures as protocells which are being produced in vast numbers as they form and decompose in continuous cycles driven by a variety of impinging, free-energy sources. This chapter describes how thermodynamic principles can be used to test the feasibility of a proposed mechanism by which random polymers can be synthesized. There is a current consensus that early life may have passed through a phase in which RNA served as a ribozyme catalyst, as a replicating system, and as a means for storing and expressing genetic information. For this reason, we will use RNA as a model polymer, but condensation reactions also produce peptide bonds and oligopeptides. At some point in the evolutionary steps leading to life, peptides and RNA formed complexes with novel functional properties beyond those of the individual molecular species.

Functional Hydration Behavior: Interrelation between Hydration and Molecular Properties at Lipid Membrane Interfaces

Water is an abundant commodity and has various important functions. It stabilizes the structure of biological macromolecules, controls biochemical activities, and regulates interfacial/intermolecular interactions. Common aspects of interfacial water can be obtained by overviewing fundamental functions and properties at different temporal and spatial scales. It is important to understand the hydrogen bonding and structural properties of water and to evaluate the individual molecular species having different hydration properties. Water molecules form hydrogen bonds with biomolecules and contribute to the adjustment of their properties, such as surface charge, hydrophilicity, and structural flexibility. In this review, the fundamental properties of water molecules and the methods used for the analyses of water dynamics are summarized. In particular, the interrelation between the hydration properties, determined by molecules, and the properties of molecules, determined by their hydration properties, are discussed using the lipid membrane as an example. Accordingly, interesting water functions are introduced that provide beneficial information in the fields of biochemistry, medicine, and food chemistry.

Effects of Population Dynamics on Establishment of a Restriction-Modification System in a Bacterial Host

In vivo dynamics of protein levels in bacterial cells depend on both intracellular regulation and relevant population dynamics. Such population dynamics effects, e.g., interplay between cell and plasmid division rates, are, however, often neglected in modeling gene expression regulation. Including them in a model introduces additional parameters shared by the dynamical equations, which can significantly increase dimensionality of the parameter inference. We here analyse the importance of these effects, on a case of bacterial restriction-modification (R-M) system. We redevelop our earlier minimal model of this system gene expression regulation, based on a thermodynamic and dynamic system modeling framework, to include the population dynamics effects. To resolve the problem of effective coupling of the dynamical equations, we propose a “mean-field-like” procedure, which allows determining only part of the parameters at a time, by separately fitting them to expression dynamics data of individual molecular species. We show that including the interplay between kinetics of cell division and plasmid replication is necessary to explain the experimental measurements. Moreover, neglecting population dynamics effects can lead to falsely identifying non-existent regulatory mechanisms. Our results call for advanced methods to reverse-engineer intracellular regulation from dynamical data, which would also take into account the population dynamics effects.

Molecular structural diversity of mitochondrial cardiolipins

Current strategies used to quantitatively describe the biological diversity of lipids by mass spectrometry are often limited in assessing the exact structural variability of individual molecular species in detail. A major challenge is represented by the extensive isobaric overlap present among lipids, hampering their accurate identification. This is especially true for cardiolipins, a mitochondria-specific class of phospholipids, which are functionally involved in many cellular functions, including energy metabolism, cristae structure, and apoptosis. Substituted with four fatty acyl side chains, cardiolipins offer a particularly high potential to achieve complex mixtures of molecular species. Here, we demonstrate how systematically generated high-performance liquid chromatography-mass spectral data can be utilized in a mathematical structural modeling approach, to comprehensively analyze and characterize the molecular diversity of mitochondrial cardiolipin compositions in cell culture and disease models, cardiolipin modulation experiments, and a broad variety of frequently studied model organisms.