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Cells Feb 2023Idiopathic pulmonary fibrosis (IPF) is a representative disease that causes fibrosis of the lungs. Its pathogenesis is thought to be characterized by sustained injury to... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is a representative disease that causes fibrosis of the lungs. Its pathogenesis is thought to be characterized by sustained injury to alveolar epithelial cells and the resultant abnormal tissue repair, but it has not been fully elucidated. IPF is currently difficult to cure and is known to follow a chronic progressive course, with the patient's survival period estimated at about three years. The disease occasionally exacerbates acutely, leading to a fatal outcome. In recent years, it has become evident that lipid metabolism is involved in the fibrosis of lungs, and various reports have been made at the cellular level as well as at the organic level. The balance among eicosanoids, sphingolipids, and lipid composition has been reported to be involved in fibrosis, with particularly close attention being paid to a bioactive lipid "lysophosphatidic acid (LPA)" and its pathway. LPA signals are found in a wide variety of cells, including alveolar epithelial cells, vascular endothelial cells, and fibroblasts, and have been reported to intensify pulmonary fibrosis via LPA receptors. For instance, in alveolar epithelial cells, LPA signals reportedly induce mitochondrial dysfunction, leading to epithelial damage, or induce the transcription of profibrotic cytokines. Based on these mechanisms, LPA receptor inhibitors and the metabolic enzymes involved in LPA formation are now considered targets for developing novel means of IPF treatment. Advances in basic research on the relationships between fibrosis and lipid metabolism are opening the path to new therapies targeting lipid metabolism in the treatment of IPF.
Topics: Humans; Lipid Metabolism; Endothelial Cells; Idiopathic Pulmonary Fibrosis; Lysophospholipids; Fibrosis
PubMed: 36831215
DOI: 10.3390/cells12040548 -
The Journal of Biological Chemistry Jan 2022The diversity of glycerophospholipid species in cellular membranes is immense and affects various biological functions. Glycerol-3-phosphate acyltransferases (GPATs) and... (Review)
Review
The diversity of glycerophospholipid species in cellular membranes is immense and affects various biological functions. Glycerol-3-phosphate acyltransferases (GPATs) and lysophospholipid acyltransferases (LPLATs), in concert with phospholipase As enzymes, contribute to this diversity via selective esterification of fatty acyl chains at the sn-1 or sn-2 positions of membrane phospholipids. These enzymes are conserved across all kingdoms, and in mammals four GPATs of the 1-acylglycerol-3-phosphate O-acyltransferase (AGPAT) family and at least 14 LPLATs, either of the AGPAT or the membrane-bound O-acyltransferase (MBOAT) families, have been identified. Here we provide an overview of the biochemical and biological activities of these mammalian enzymes, including their predicted structures, involvements in human diseases, and essential physiological roles as revealed by gene-deficient mice. Recently, the nomenclature used to refer to these enzymes has generated some confusion due to the use of multiple names to refer to the same enzyme and instances of the same name being used to refer to completely different enzymes. Thus, this review proposes a more uniform LPLAT enzyme nomenclature, as well as providing an update of recent advances made in the study of LPLATs, continuing from our JBC mini review in 2009.
Topics: 1-Acylglycerophosphocholine O-Acyltransferase; Animals; Glycerophospholipids; Humans; Lysophospholipids; Terminology as Topic
PubMed: 34890643
DOI: 10.1016/j.jbc.2021.101470 -
Journal of Lipid Research Jul 2015Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that acts either as an intracellular messenger or as a ligand for its membrane receptors. S1P is a normal... (Review)
Review
Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that acts either as an intracellular messenger or as a ligand for its membrane receptors. S1P is a normal constituent of blood, where it is found both in plasma and blood cells. Compared with other cell types, sphingolipid metabolism in erythrocytes and platelets has unique features that allow the erythrocytes and platelets to accumulate S1P. In plasma, S1P is bound mainly to HDLs and albumin. Of note, metabolism and biological activity of S1P is to a large extent affected by the type of its carrier. Plasma S1P is characterized by a short half-life, indicating rapid clearance by degradative enzymes and the presence of high-capacity sources involved in maintaining its high concentration. These sources include blood cells, vascular endothelium, and hepatocytes. However, the extent to which each of these contributes to the plasma pool of S1P is a matter of debate. Circulating S1P plays a significant physiological role. It was found to be the key regulator of lymphocyte trafficking, endothelial barrier function, and vascular tone. The purpose of this review is to summarize the present state of knowledge on the metabolism, transport, and origin of plasma S1P, and to discuss the mechanisms regulating its homeostasis in blood.
Topics: Animals; Blood Cells; Humans; Lysophospholipids; Sphingosine
PubMed: 26014962
DOI: 10.1194/jlr.R059543 -
Nature Chemical Biology Jul 2010Sphingolipids comprise a complex family of naturally occurring molecules that are enriched in lipid rafts and contribute to their unique biochemical properties. Membrane... (Review)
Review
Sphingolipids comprise a complex family of naturally occurring molecules that are enriched in lipid rafts and contribute to their unique biochemical properties. Membrane sphingolipids also serve as a reservoir for bioactive metabolites including sphingosine, ceramide, sphingosine-1-phosphate and ceramide-1-phosphate. Among these, sphingosine-1-phosphate has emerged as a central regulator of mammalian biology. Sphingosine-1-phosphate is essential for mammalian brain and cardiac development and for maturation of the systemic circulatory system and lymphatics. In addition, sphingosine-1-phosphate contributes to trafficking and effector functions of lymphocytes and other hematopoietic cells and protects against various forms of tissue injury. However, sphingosine-1-phosphate is also an oncogenic lipid that promotes tumor growth and progression. Recent preclinical and clinical investigations using pharmacological agents that target sphingosine-1-phosphate, its receptors and the enzymes required for its biosynthesis and degradation demonstrate the promise and potential risks of modulating sphingosine-1-phosphate signaling in treatment strategies for autoimmunity, cancer, cardiovascular disease and other pathological conditions.
Topics: Animals; Gene Expression Regulation; Humans; Lysophospholipids; Sphingolipids; Sphingosine
PubMed: 20559316
DOI: 10.1038/nchembio.392 -
Cell Biochemistry and Biophysics Sep 2021Lysophosphatidylserine (LysoPS) is an emerging lysophospholipid (LPL) mediator, which acts through G protein-coupled receptors, like lysophosphatidic acid (LPA) and... (Review)
Review
Lysophosphatidylserine (LysoPS) is an emerging lysophospholipid (LPL) mediator, which acts through G protein-coupled receptors, like lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P). LysoPS is detected in various tissues and cells and thought to be produced mainly by the deacylation of phosphatidylserine. LysoPS has been known to stimulate degranulation of mast cells. Recently, four LysoPS-specific G protein-coupled receptors (GPCRs) were identified. These GPCRs belong to the P2Y family which covers receptors for nucleotides and LPLs and are predominantly expressed in immune cells such as lymphocytes and macrophages. Studies on knockout mice of these GPCRs have revealed that LysoPS has immune-modulatory functions. Up-regulation of a LysoPS-producing enzyme, PS-specific phospholipase A, was frequently observed in situations where the immune system is activated including autoimmune diseases and organ transplantations. Therefore, modulation of LysoPS signaling appears to be a promising method for providing therapies for the treatment of immune diseases. In this review, we summarize the biology of LysoPS-producing enzymes and receptors, recent developments in LysoPS signal modulators, and prospects for future therapeutic applications.
Topics: Lysophospholipids
PubMed: 34129148
DOI: 10.1007/s12013-021-00988-9 -
BMC Bioinformatics Aug 2006Sphingosine 1-phosphate (S1P), a lysophospholipid, is involved in various cellular processes such as migration, proliferation, and survival. To date, the impact of S1P...
Text mining of full-text journal articles combined with gene expression analysis reveals a relationship between sphingosine-1-phosphate and invasiveness of a glioblastoma cell line.
BACKGROUND
Sphingosine 1-phosphate (S1P), a lysophospholipid, is involved in various cellular processes such as migration, proliferation, and survival. To date, the impact of S1P on human glioblastoma is not fully understood. Particularly, the concerted role played by matrix metalloproteinases (MMP) and S1P in aggressive tumor behavior and angiogenesis remains to be elucidated.
RESULTS
To gain new insights in the effect of S1P on angiogenesis and invasion of this type of malignant tumor, we used microarrays to investigate the gene expression in glioblastoma as a response to S1P administration in vitro. We compared the expression profiles for the same cell lines under the influence of epidermal growth factor (EGF), an important growth factor. We found a set of 72 genes that are significantly differentially expressed as a unique response to S1P. Based on the result of mining full-text articles from 20 scientific journals in the field of cancer research published over a period of five years, we inferred gene-gene interaction networks for these 72 differentially expressed genes. Among the generated networks, we identified a particularly interesting one. It describes a cascading event, triggered by S1P, leading to the transactivation of MMP-9 via neuregulin-1 (NRG-1), vascular endothelial growth factor (VEGF), and the urokinase-type plasminogen activator (uPA). This interaction network has the potential to shed new light on our understanding of the role played by MMP-9 in invasive glioblastomas.
CONCLUSION
Automated extraction of information from biological literature promises to play an increasingly important role in biological knowledge discovery. This is particularly true for high-throughput approaches, such as microarrays, and for combining and integrating data from different sources. Text mining may hold the key to unraveling previously unknown relationships between biological entities and could develop into an indispensable instrument in the process of formulating novel and potentially promising hypotheses.
Topics: Cell Line, Tumor; Data Interpretation, Statistical; Databases, Bibliographic; Epidermal Growth Factor; Gene Expression Regulation, Neoplastic; Glioblastoma; Humans; Lysophospholipids; Matrix Metalloproteinase 9; Neoplasm Invasiveness; Neovascularization, Pathologic; Oligonucleotide Array Sequence Analysis; Protein Interaction Mapping; Sphingosine
PubMed: 16901352
DOI: 10.1186/1471-2105-7-373 -
Experimental Biology and Medicine... Aug 2021Stem cells possess unique biological characteristics such as the ability to self-renew and to undergo multilineage differentiation into specialized cells. Whereas... (Review)
Review
Stem cells possess unique biological characteristics such as the ability to self-renew and to undergo multilineage differentiation into specialized cells. Whereas embryonic stem cells (ESC) can differentiate into all cell types of the body, somatic stem cells (SSC) are a population of stem cells located in distinct niches throughout the body that differentiate into the specific cell types of the tissue in which they reside in. SSC function mainly to restore cells as part of normal tissue homeostasis or to replenish cells that are damaged due to injury. Cancer stem-like cells (CSC) are said to be analogous to SSC in this manner where tumor growth and progression as well as metastasis are fueled by a small population of CSC that reside within the corresponding tumor. Moreover, emerging evidence indicates that CSC are inherently resistant to chemo- and radiotherapy that are often the cause of cancer relapse. Hence, major research efforts have been directed at identifying CSC populations in different cancer types and understanding their biology. Many factors are thought to regulate and maintain cell stemness, including bioactive lysophospholipids such as lysophosphatidic acid (LPA). In this review, we discuss some of the newly discovered functions of LPA not only in the regulation of CSC but also normal SSC, the similarities in these regulatory functions, and how these discoveries can pave way to the development of novel therapies in cancer and regenerative medicine.
Topics: Animals; Cell Differentiation; Cell Proliferation; Humans; Lysophospholipids; Neoplasms; Neoplastic Stem Cells
PubMed: 34038224
DOI: 10.1177/15353702211019283 -
PloS One 2022The abnormal posterior vitreous detachment (PVD) is speculated as an important mechanism of the development of the epiretinal membrane (ERM). However, there is only...
The abnormal posterior vitreous detachment (PVD) is speculated as an important mechanism of the development of the epiretinal membrane (ERM). However, there is only limited information about the molecular mechanism. Sphingosine-1-phosphate (S1P) is a mediator of the mechanosensitive response in several cell types that may have a role in the pathogenesis of ERM during abnormal PVD. Therefore, we evaluated the expression of S1P in the human ERM and the role of S1P in cultured human Muller glial cells. Among 24 ERM specimens, seven specimens (29.2%) exhibited S1P expression. Patients with secondary ERM or ellipsoid zone defects, which suggest abnormal PVD presented a significantly higher S1P+ cell density (secondary ERM: 128.20 ± 135.61 and 9.68 ± 36.01 cells, p = 0.002; EZ defects: 87.56 ± 117.79 vs 2.80 ± 8.85, p = 0.036). The addition of S1P increased the migrative ability and expression of N-cadherin and α-SMA in human Muller glial cells, suggesting S1P is a potential causative molecule for the development of ERM during abnormal PVD.
Topics: Epiretinal Membrane; Humans; Lysophospholipids; Sphingosine; Vitreous Detachment
PubMed: 36044534
DOI: 10.1371/journal.pone.0273674 -
Biochimica Et Biophysica Acta Jan 2013The lysophospholipids sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) signal through G-protein coupled receptors (GPCRs) which couple to multiple... (Review)
Review
The lysophospholipids sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) signal through G-protein coupled receptors (GPCRs) which couple to multiple G-proteins and their effectors. These GPCRs are quite efficacious in coupling to the Gα(12/13) family of G-proteins, which stimulate guanine nucleotide exchange factors (GEFs) for RhoA. Activated RhoA subsequently regulates downstream enzymes that transduce signals which affect the actin cytoskeleton, gene expression, cell proliferation and cell survival. Remarkably many of the enzymes regulated downstream of RhoA either use phospholipids as substrates (e.g. phospholipase D, phospholipase C-epsilon, PTEN, PI3 kinase) or are regulated by phospholipid products (e.g. protein kinase D, Akt). Thus lysophospholipids signal from outside of the cell and control phospholipid signaling processes within the cell that they target. Here we review evidence suggesting an integrative role for RhoA in responding to lysophospholipids upregulated in the pathophysiological environment, and in transducing this signal to cellular responses through effects on phospholipid regulatory or phospholipid regulated enzymes. This article is part of a Special Issue entitled Advances in Lysophospholipid Research.
Topics: Animals; Humans; Lipid Metabolism; Lysophospholipids; Myocardium; Receptors, Lysophospholipid; Signal Transduction; Sphingosine; rhoA GTP-Binding Protein
PubMed: 22986288
DOI: 10.1016/j.bbalip.2012.09.004 -
Neuron Feb 2015The brain is composed of many lipids with varied forms that serve not only as structural components but also as essential signaling molecules. Lysophosphatidic acid... (Review)
Review
The brain is composed of many lipids with varied forms that serve not only as structural components but also as essential signaling molecules. Lysophosphatidic acid (LPA) is an important bioactive lipid species that is part of the lysophospholipid (LP) family. LPA is primarily derived from membrane phospholipids and signals through six cognate G protein-coupled receptors (GPCRs), LPA1-6. These receptors are expressed on most cell types within central and peripheral nervous tissues and have been functionally linked to many neural processes and pathways. This Review covers a current understanding of LPA signaling in the nervous system, with particular focus on the relevance of LPA to both physiological and diseased states.
Topics: Animals; Humans; Lysophospholipids; Nervous System; Receptors, G-Protein-Coupled; Signal Transduction
PubMed: 25695267
DOI: 10.1016/j.neuron.2015.01.009