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Proceedings of the Japan Academy.... 2018Lysophospholipids (LPLs), such as lysophosphatidic acid (LPA), sphingosine 1-phosphate (S1P), and lysophosphatidylserine (LysoPS), are attracting attention as... (Review)
Review
Lysophospholipids (LPLs), such as lysophosphatidic acid (LPA), sphingosine 1-phosphate (S1P), and lysophosphatidylserine (LysoPS), are attracting attention as second-generation lipid mediators. In our laboratory, the functional roles of these lipid mediators and the mechanisms by which the levels of these mediators are regulated in vivo have been studied. Based on these studies, the clinical introduction of assays for LPLs and related proteins has been pursued and will be described in this review. Although assays of these lipids themselves are possible, autotaxin (ATX), apolipoprotein M (ApoM), and phosphatidylserine-specific phospholipase A (PS-PLA) are more promising as alternate biomarkers for LPA, S1P, and LysoPS, respectively. Presently, ATX, which produces LPA through its lysophospholipase D activity, has been shown to be a useful laboratory test for the diagnosis and staging of liver fibrosis, whereas PS-PLA and ApoM are considered to be promising clinical markers reflecting the in vivo actions induced by LysoPS and S1P.
Topics: Animals; Body Fluids; Humans; Laboratories; Lysophospholipids
PubMed: 30541965
DOI: 10.2183/pjab.94.025 -
Progress in Lipid Research Nov 2020Lipids are abundant and play essential roles in human health and disease. The main functions of lipids are building blocks for membrane biogenesis. However, lipids are... (Review)
Review
Lipids are abundant and play essential roles in human health and disease. The main functions of lipids are building blocks for membrane biogenesis. However, lipids are also metabolized to produce signaling molecules. Here, we discuss the emerging roles of circulating lysophospholipids. These lysophospholipids consist of lysoglycerophospholipids and lysosphingolipids. They are both present in cells at low concentration, but their concentrations in extracellular fluids are significantly higher. The biological functions of some of these lysophospholipids have been recently revealed. Remarkably, some of the lysophospholipids play pivotal signaling roles as well as being precursors for membrane biogenesis. Revealing how circulating lysophospholipids are produced, released, transported, and utilized in multi-organ systems is critical to understand their functions. The discovery of enzymes, carriers, transporters, and membrane receptors for these lysophospholipids has shed light on their physiological significance. In this review, we summarize the biological roles of these lysophospholipids via discussing about the proteins regulating their functions. We also discuss about their potential impacts to human health and diseases.
Topics: Animals; Biomarkers; Carrier Proteins; Humans; Lysophospholipids; Signal Transduction
PubMed: 33068601
DOI: 10.1016/j.plipres.2020.101068 -
Advances in Microbial Physiology 2023Lysophospholipids (LPLs) are lipid-derived metabolic intermediates in the cell membrane. The biological functions of LPLs are distinct from their corresponding... (Review)
Review
Lysophospholipids (LPLs) are lipid-derived metabolic intermediates in the cell membrane. The biological functions of LPLs are distinct from their corresponding phospholipids. In eukaryotic cells LPLs are important bioactive signaling molecules that regulate many important biological processes, but in bacteria the function of LPLs is still not fully defined. Bacterial LPLs are usually present in cells in very small amounts, but can strongly increase under certain environmental conditions. In addition to their basic function as precursors in membrane lipid metabolism, the formation of distinct LPLs contributes to the proliferation of bacteria under harsh circumstances or may act as signaling molecules in bacterial pathogenesis. This review provides an overview of the current knowledge of the biological functions of bacterial LPLs including lysoPE, lysoPA, lysoPC, lysoPG, lysoPS and lysoPI in bacterial adaptation, survival, and host-microbe interactions.
Topics: Lysophospholipids; Signal Transduction; Lipid Metabolism; Bacteria; Biological Phenomena
PubMed: 36948653
DOI: 10.1016/bs.ampbs.2022.10.001 -
Science (New York, N.Y.) Nov 2001Upon cell activation, membrane phospholipids are metabolized into potent lysophospholipid (LP) mediators, such as sphingosine 1-phosphate and lysophosphatidic acid. LPs... (Review)
Review
Upon cell activation, membrane phospholipids are metabolized into potent lysophospholipid (LP) mediators, such as sphingosine 1-phosphate and lysophosphatidic acid. LPs fulfill signaling roles in organisms as diverse as yeast and humans. The recent discovery of G protein-coupled receptors for LPs in higher eukaryotes, and their involvement in regulating diverse processes such as angiogenesis, cardiac development, neuronal survival, and immunity, has stimulated growing interest in these lipid mediators. LP receptor biology has generated insights into fundamental cellular mechanisms and may provide therapeutic targets for drug development.
Topics: Animals; Heterotrimeric GTP-Binding Proteins; Humans; Lysophospholipids; Phylogeny; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Receptors, Lysophosphatidic Acid; Receptors, Lysophospholipid; Signal Transduction; Sphingosine
PubMed: 11729304
DOI: 10.1126/science.1065323 -
Biochimica Et Biophysica Acta.... Jul 2020
Topics: Animals; Humans; Lysophospholipids; Receptors, Lysophospholipid
PubMed: 32179098
DOI: 10.1016/j.bbalip.2020.158697 -
The Journal of Membrane Biology Oct 2020Lysophospholipids are potent hormone-like signalling biological lipids that regulate many important biological processes in mammals (including humans). Lysophosphatidic... (Review)
Review
Lysophospholipids are potent hormone-like signalling biological lipids that regulate many important biological processes in mammals (including humans). Lysophosphatidic acid and sphingosine-1-phosphate represent the best studied examples for this lipid class, and their metabolic enzymes and/or cognate receptors are currently under clinical investigation for treatment of various neurological and autoimmune diseases in humans. Over the past two decades, the lysophsophatidylserines (lyso-PSs) have emerged as yet another biologically important lysophospholipid, and deregulation in its metabolism has been linked to various human pathophysiological conditions. Despite its recent emergence, an exhaustive review summarizing recent advances on lyso-PSs and the biological pathways that this bioactive lysophospholipid regulates has been lacking. To address this, here, we summarize studies that led to the discovery of lyso-PS as a potent signalling biomolecule, and discuss the structure, its detection in biological systems, and the biodistribution of this lysophospholipid in various mammalian systems. Further, we describe in detail the enzymatic pathways that are involved in the biosynthesis and degradation of this lipid and the putative lyso-PS receptors reported in the literature. Finally, we discuss the various biological pathways directly regulated by lyso-PSs in mammals and prospect new questions for this still emerging biomedically important signalling lysophospholipid.
Topics: Animals; Biological Transport; Cell Degranulation; Humans; Lipid Metabolism; Lysophospholipids; Macrophages; Mast Cells; Membrane Lipids; Metabolic Networks and Pathways; Oxidation-Reduction; Phagocytosis; Signal Transduction; Structure-Activity Relationship
PubMed: 32767057
DOI: 10.1007/s00232-020-00133-2 -
Mini Reviews in Medicinal Chemistry Jan 2012The in vivo concentration of lysophospholipids (LPL) such as lysophosphatidylcholine (LPC) increases under different pathological conditions and, thus, LPL attract... (Review)
Review
The in vivo concentration of lysophospholipids (LPL) such as lysophosphatidylcholine (LPC) increases under different pathological conditions and, thus, LPL attract nowadays considerable diagnostic and pharmacological interest. LPL are particularly interesting because they possess pro- and anti-inflammatory properties and can be generated by two completely different pathways: either by the influence of (a) phospholipases and (b) different reactive oxygen species (ROS) that are generated in significant amounts under inflammatory conditions. This review provides a summary of the mechanisms by which LPL can be generated under in vitro and in vivo conditions. The focus will be on lysophosphatidylcholine (LPC) because this LPL is most abundant among all LPL and was, thus, most intensively studied so far. Additionally, biochemical, chromatographic and spectroscopic methods of LPL and LPC determinations will be discussed. Finally, the effects of LPL as signaling molecules and their roles in different pathologies such as infertility, cancer, atherosclerosis or inflammatory diseases are discussed. Special emphasis will be on the role of LPL in reproduction failures related to poor semen quality and, in that context, the potential role of LPC as a disease-indicative molecule.
Topics: Atherosclerosis; Biomarkers; Female; Humans; Infertility; Inflammation; Lysophosphatidylcholines; Lysophospholipids; Male; Molecular Diagnostic Techniques; Neoplasms; Signal Transduction
PubMed: 22070693
DOI: 10.2174/138955712798868931 -
Biochimica Et Biophysica Acta Jan 2013Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), two of the best-studied lysophospholipids, are known to influence diverse biological events, including... (Review)
Review
Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), two of the best-studied lysophospholipids, are known to influence diverse biological events, including organismal development as well as function and pathogenesis within multiple organ systems. These functional roles are due to a family of at least 11 G protein-coupled receptors (GPCRs), named LPA(1-6) and S1P(1-5), which are widely distributed throughout the body and that activate multiple effector pathways initiated by a range of heterotrimeric G proteins including G(i/o), G(12/13), G(q) and G(s), with actual activation dependent on receptor subtypes. In the central nervous system (CNS), a major locus for these signaling pathways, LPA and S1P have been shown to influence myriad responses in neurons and glial cell types through their cognate receptors. These receptor-mediated activities can contribute to disease pathogenesis and have therapeutic relevance to human CNS disorders as demonstrated for multiple sclerosis (MS) and possibly others that include congenital hydrocephalus, ischemic stroke, neurotrauma, neuropsychiatric disorders, developmental disorders, seizures, hearing loss, and Sandhoff disease, based upon the experimental literature. In particular, FTY720 (fingolimod, Gilenya, Novartis Pharma, AG) that becomes an analog of S1P upon phosphorylation, was approved by the FDA in 2010 as a first oral treatment for MS, validating this class of receptors as medicinal targets. This review will provide an overview and update on the biological functions of LPA and S1P signaling in the CNS, with a focus on results from studies using genetic null mutants for LPA and S1P receptors. This article is part of a Special Issue entitled Advances in Lysophospholipid Research.
Topics: Central Nervous System; Humans; Lysophospholipids; Nervous System Diseases; Receptors, Lysophospholipid; Receptors, Lysosphingolipid
PubMed: 22884303
DOI: 10.1016/j.bbalip.2012.07.015 -
Biochimica Et Biophysica Acta.... Nov 2017Lysophospholipids (LPLs) are metabolic intermediates in bacterial phospholipid turnover. Distinct from their diacyl counterparts, these inverted cone-shaped molecules... (Review)
Review
Lysophospholipids (LPLs) are metabolic intermediates in bacterial phospholipid turnover. Distinct from their diacyl counterparts, these inverted cone-shaped molecules share physical characteristics of detergents, enabling modification of local membrane properties such as curvature. The functions of LPLs as cellular growth factors or potent lipid mediators have been extensively demonstrated in eukaryotic cells but are still undefined in bacteria. In the envelope of Gram-negative bacteria, LPLs are derived from multiple endogenous and exogenous sources. Although several flippases that move non-glycerophospholipids across the bacterial inner membrane were characterized, lysophospholipid transporter LplT appears to be the first example of a bacterial protein capable of facilitating rapid retrograde translocation of lyso forms of glycerophospholipids across the cytoplasmic membrane in Gram-negative bacteria. LplT transports lyso forms of the three bacterial membrane phospholipids with comparable efficiency, but excludes other lysolipid species. Once a LPL is flipped by LplT to the cytoplasmic side of the inner membrane, its diacyl form is effectively regenerated by the action of a peripheral enzyme, acyl-ACP synthetase/LPL acyltransferase (Aas). LplT-Aas also mediates a novel cardiolipin remodeling by converting its two lyso derivatives, diacyl or deacylated cardiolipin, to a triacyl form. This coupled remodeling system provides a unique bacterial membrane phospholipid repair mechanism. Strict selectivity of LplT for lyso lipids allows this system to fulfill efficient lipid repair in an environment containing mostly diacyl phospholipids. A rocker-switch model engaged by a pair of symmetric ion-locks may facilitate alternating substrate access to drive LPL flipping into bacterial cells. This article is part of a Special Issue entitled: Bacterial Lipids edited by Russell E. Bishop.
Topics: Bacterial Proteins; Biological Transport; Carbon-Sulfur Ligases; Cell Wall; Gram-Negative Bacteria; Lipogenesis; Lysophospholipids; Phospholipid Transfer Proteins; Signal Transduction; Substrate Specificity
PubMed: 27956138
DOI: 10.1016/j.bbalip.2016.11.015 -
International Immunology Aug 2019AbstractSphingosine 1-phosphate (S1P), a sphingolipid mediator, regulates various cellular functions via high-affinity G protein-coupled receptors, S1P1-5. The S1P-S1P... (Review)
Review
AbstractSphingosine 1-phosphate (S1P), a sphingolipid mediator, regulates various cellular functions via high-affinity G protein-coupled receptors, S1P1-5. The S1P-S1P receptor signaling system plays important roles in lymphocyte trafficking and maintenance of vascular integrity, thus contributing to the regulation of complex inflammatory processes. S1P is enriched in blood and lymph while maintained low in intracellular or interstitial fluids, creating a steep S1P gradient that is utilized to facilitate efficient egress of lymphocytes from lymphoid organs. Blockage of the S1P-S1P receptor signaling system results in a marked decrease in circulating lymphocytes because of a failure of lymphocyte egress from lymphoid organs. This provides a basis of immunomodulatory drugs targeting S1P1 receptor such as FTY720, an immunosuppressive drug approved in 2010 as the first oral treatment for relapsing-remitting multiple sclerosis. The S1P-S1P receptor signaling system also plays important roles in maintenance of vascular integrity since it suppresses sprouting angiogenesis and regulates vascular permeability. Dysfunction of the S1P-S1P receptor signaling system results in various vascular defects, such as exaggerated angiogenesis in developing retina and augmented inflammation due to increased permeability. Endothelial-specific deletion of S1P1 receptor in mice fed high-fat diet leads to increased formation of atherosclerotic lesions. This review highlights the importance of the S1P-S1P receptor signaling system in inflammatory processes. We also describe our recent findings regarding a specific S1P chaperone, apolipoprotein M, that anchors to high-density lipoprotein and contributes to shaping the endothelial-protective and anti-inflammatory properties of high-density lipoprotein.
Topics: Animals; Humans; Inflammation; Lysophospholipids; Signal Transduction; Sphingosine; Sphingosine-1-Phosphate Receptors
PubMed: 31049553
DOI: 10.1093/intimm/dxz037