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Biomolecules Oct 2020Phospholipases are a family of lipid-altering enzymes that can either reduce or increase bioactive lipid levels. Bioactive lipids elicit signaling responses, activate... (Review)
Review
Phospholipases are a family of lipid-altering enzymes that can either reduce or increase bioactive lipid levels. Bioactive lipids elicit signaling responses, activate transcription factors, promote G-coupled-protein activity, and modulate membrane fluidity, which mediates cellular function. Phospholipases and the bioactive lipids they produce are important regulators of immune cell activity, dictating both pro-inflammatory and pro-resolving activity. During atherosclerosis, pro-inflammatory and pro-resolving activities govern atherosclerosis progression and regression, respectively. This review will look at the interface of phospholipase activity, immune cell function, and atherosclerosis.
Topics: Atherosclerosis; GTP-Binding Proteins; Humans; Inflammation; Lipids; Macrophages; Membrane Fluidity; Phospholipases; Signal Transduction
PubMed: 33076403
DOI: 10.3390/biom10101449 -
International Journal of Molecular... Jun 2017Persistent low grade immune activation and chronic inflammation are nowadays considered main driving forces of the progressive immunologic failure in effective... (Review)
Review
Persistent low grade immune activation and chronic inflammation are nowadays considered main driving forces of the progressive immunologic failure in effective antiretroviral therapy treated HIV-1 infected individuals. Among the factors contributing to this phenomenon, microbial translocation has emerged as a key driver of persistent immune activation. Indeed, the rapid depletion of gastrointestinal CD4⁺ T lymphocytes occurring during the early phases of infection leads to a deterioration of the gut epithelium followed by the translocation of microbial products into the systemic circulation and the subsequent activation of innate immunity. In this context, monocytes/macrophages are increasingly recognized as an important source of inflammation, linked to HIV-1 disease progression and to non-AIDS complications, such as cardiovascular disease and neurocognitive decline, which are currently main challenges in treated patients. Lipid signaling plays a central role in modulating monocyte/macrophage activation, immune functions and inflammatory responses. Phospholipase-mediated phospholipid hydrolysis leads to the production of lipid mediators or second messengers that affect signal transduction, thus regulating a variety of physiologic and pathophysiologic processes. In this review, we discuss the contribution of phospholipases to monocyte/macrophage activation in the context of HIV-1 infection, focusing on their involvement in virus-associated chronic inflammation and co-morbidities.
Topics: Bacterial Translocation; CD4-Positive T-Lymphocytes; Cardiovascular Diseases; Cell Differentiation; Cytokines; HIV Infections; HIV-1; Humans; Immunity, Innate; Inflammation; Macrophages; Monocytes; Neurocognitive Disorders; Phospholipases; Signal Transduction
PubMed: 28661459
DOI: 10.3390/ijms18071390 -
Genes Jun 2022Phospholipase C is an enzyme that catalyzes the hydrolysis of glycerophospholipids and can be classified as phosphoinositide-specific PLC (PI-PLC) and non-specific PLC...
Phospholipase C is an enzyme that catalyzes the hydrolysis of glycerophospholipids and can be classified as phosphoinositide-specific PLC (PI-PLC) and non-specific PLC (NPC), depending on its hydrolytic substrate. In maize, the function of phospholipase C has not been well characterized. In this study, the phospholipase C inhibitor neomycin sulfate (NS, 100 mM) was applied to maize seedlings to investigate the function of maize PLC. Under the treatment of neomycin sulfate, the growth and development of maize seedlings were impaired, and the leaves were gradually etiolated and wilted. The analysis of physiological and biochemical parameters revealed that inhibition of phospholipase C affected photosynthesis, photosynthetic pigment accumulation, carbon metabolism and the stability of the cell membrane. High-throughput RNA-seq was conducted, and differentially expressed genes (DEGS) were found significantly enriched in photosynthesis and carbon metabolism pathways. When phospholipase C activity was inhibited, the expression of genes related to photosynthetic pigment accumulation was decreased, which led to lowered chlorophyll. Most of the genes related to PSI, PSII and TCA cycles were down-regulated and the net photosynthesis was decreased. Meanwhile, genes related to starch and sucrose metabolism, the pentose phosphate pathway and the glycolysis/gluconeogenesis pathway were up-regulated, which explained the reduction of starch and total soluble sugar content in the leaves of maize seedlings. These findings suggest that phospholipase C plays a key role in photosynthesis and the growth and development of maize seedlings.
Topics: Carbon; Neomycin; Photosynthesis; Seedlings; Starch; Type C Phospholipases; Zea mays
PubMed: 35741773
DOI: 10.3390/genes13061011 -
Biochimica Et Biophysica Acta Dec 2014The classical regard of lipid droplets as mere static energy-storage organelles has evolved dramatically. Nowadays these organelles are known to participate in key... (Review)
Review
The classical regard of lipid droplets as mere static energy-storage organelles has evolved dramatically. Nowadays these organelles are known to participate in key processes of cell homeostasis, and their abnormal regulation is linked to several disorders including metabolic diseases (diabetes, obesity, atherosclerosis or hepatic steatosis), inflammatory responses in leukocytes, cancer development and neurodegenerative diseases. Hence, the importance of unraveling the cell mechanisms controlling lipid droplet biosynthesis, homeostasis and degradation seems evident Phospholipase A2s, a family of enzymes whose common feature is to hydrolyze the fatty acid present at the sn-2 position of phospholipids, play pivotal roles in cell signaling and inflammation. These enzymes have recently emerged as key regulators of lipid droplet homeostasis, regulating their formation at different levels. This review summarizes recent results on the roles that various phospholipase A2 forms play in the regulation of lipid droplet biogenesis under different conditions. These roles expand the already wide range of functions that these enzymes play in cell physiology and pathophysiology.
Topics: Animals; Calcium; Humans; Lipid Droplets; Models, Biological; Phospholipases A2
PubMed: 25450448
DOI: 10.1016/j.bbalip.2014.10.004 -
Biomolecules Apr 2023Among the phospholipase A (PLA) family, the secreted PLA (sPLA) family in mammals contains 11 members that exhibit unique tissue or cellular distributions and enzymatic... (Review)
Review
Among the phospholipase A (PLA) family, the secreted PLA (sPLA) family in mammals contains 11 members that exhibit unique tissue or cellular distributions and enzymatic properties. Current studies using knockout and/or transgenic mice for a nearly full set of sPLAs, in combination with comprehensive lipidomics, have revealed the diverse pathophysiological roles of sPLAs in various biological events. Individual sPLAs exert specific functions within tissue microenvironments, likely through the hydrolysis of extracellular phospholipids. Lipids are an essential biological component for skin homeostasis, and disturbance of lipid metabolism by deletion or overexpression of lipid-metabolizing enzymes or lipid-sensing receptors often leads to skin abnormalities that are easily visible on the outside. Over the past decades, our studies using knockout and transgenic mice for various sPLAs have uncovered several new aspects of these enzymes as modulators of skin homeostasis and disease. This article summarizes the roles of several sPLAs in skin pathophysiology, providing additional insight into the research fields of sPLAs, lipids, and skin biology.
Topics: Animals; Mice; Phospholipases A2, Secretory; Skin; Phospholipids; Mice, Transgenic; Mammals; Homeostasis
PubMed: 37189415
DOI: 10.3390/biom13040668 -
Progress in Lipid Research Apr 2022Cell membranes are the initial site of stimulus perception from environment and phospholipids are the basic and important components of cell membranes. Phospholipases... (Review)
Review
Cell membranes are the initial site of stimulus perception from environment and phospholipids are the basic and important components of cell membranes. Phospholipases hydrolyze membrane lipids to generate various cellular mediators. These phospholipase-derived products, such as diacylglycerol, phosphatidic acid, inositol phosphates, lysophopsholipids, and free fatty acids, act as second messengers, playing vital roles in signal transduction during plant growth, development, and stress responses. This review focuses on the structure, substrate specificities, reaction requirements, and acting mechanism of several phospholipase families. It will discuss their functional significance in plant growth, development, and stress responses. In addition, it will highlight some critical knowledge gaps in the action mechanism, metabolic and signaling roles of these phospholipases and their products in the context of plant growth, development and stress responses.
Topics: Humans; Hydrolysis; Phosphatidic Acids; Phospholipase D; Phospholipases; Phospholipids; Type C Phospholipases
PubMed: 35134459
DOI: 10.1016/j.plipres.2022.101158 -
Molecules (Basel, Switzerland) Jul 2023Phosphatidylcholine-specific phospholipase C (PC-PLC) is an enzyme that catalyzes the formation of the important secondary messengers phosphocholine and diacylglycerol... (Review)
Review
Phosphatidylcholine-specific phospholipase C (PC-PLC) is an enzyme that catalyzes the formation of the important secondary messengers phosphocholine and diacylglycerol (DAG) from phosphatidylcholine. Although PC-PLC has been linked to the progression of many pathological conditions, including cancer, atherosclerosis, inflammation and neuronal cell death, studies of PC-PLC on the protein level have been somewhat neglected with relatively scarce data. To date, the human gene expressing PC-PLC has not yet been found, and the only protein structure of PC-PLC that has been solved was from (PC-PLC). Nonetheless, there is evidence for PC-PLC activity as a human functional equivalent of its prokaryotic counterpart. Additionally, inhibitors of PC-PLC have been developed as potential therapeutic agents. The most notable classes include 2-aminohydroxamic acids, xanthates, ,'-hydroxyureas, phospholipid analogues, 1,4-oxazepines, pyrido[3,4-]indoles, morpholinobenzoic acids and univalent ions. However, many medicinal chemistry studies lack evidence for their cellular and in vivo effects, which hampers the progression of the inhibitors towards the clinic. This review outlines the pathological implications of PC-PLC and highlights current progress and future challenges in the development of PC-PLC inhibitors from the literature.
Topics: Humans; Type C Phospholipases; Phosphatidylcholines
PubMed: 37570610
DOI: 10.3390/molecules28155637 -
Frontiers in Immunology 2023Phospholipase A and acyltransferase (PLAAT) 4 is a class II tumor suppressor with phospholipid metabolizing abilities. It was characterized in late 2000s, and has since... (Review)
Review
Phospholipase A and acyltransferase (PLAAT) 4 is a class II tumor suppressor with phospholipid metabolizing abilities. It was characterized in late 2000s, and has since been referred to as 'tazarotene-induced gene 3' (TIG3) or 'retinoic acid receptor responder 3' (RARRES3) as a key downstream effector of retinoic acid signaling. Two decades of research have revealed the complexity of its function and regulatory roles in suppressing tumorigenesis. However, more recent findings have also identified PLAAT4 as a key anti-microbial effector enzyme acting downstream of interferon regulatory factor 1 (IRF1) and interferons (IFNs), favoring protection from virus and parasite infections. Unveiling the molecular mechanisms underlying its action may thus open new therapeutic avenues for the treatment of both cancer and infectious diseases. Herein, we aim to summarize a brief history of PLAAT4 discovery, its transcriptional regulation, and the potential mechanisms in tumor prevention and anti-pathogen defense, and discuss potential future directions of PLAAT4 research toward the development of therapeutic approaches targeting this enzyme with pleiotropic functions.
Topics: Receptors, Retinoic Acid; Genes, Tumor Suppressor; Tretinoin; Acyltransferases; Phospholipases
PubMed: 37063830
DOI: 10.3389/fimmu.2023.1107239 -
Prostaglandins & Other Lipid Mediators Feb 2022Bone modeling can be modulated by lipid signals such as arachidonic acid (AA) and its cyclooxygenase 2 (COX2) metabolite, prostaglandin E (PGE), which are recognized...
Bone modeling can be modulated by lipid signals such as arachidonic acid (AA) and its cyclooxygenase 2 (COX2) metabolite, prostaglandin E (PGE), which are recognized mediators of optimal bone formation. Hydrolysis of AA from membrane glycerophospholipids is catalyzed by phospholipases A (PLAs). We reported that mice deficient in the Ca- independent PLAbeta (iPLAβ), encoded by Pla2g6, exhibit a low bone phenotype, but the cause for this remains to be identified. Here, we examined the mechanistic and molecular roles of iPLAβ in bone formation using bone marrow stromal cells and calvarial osteoblasts from WT and iPLAβ-deficient mice, and the MC3T3-E1 osteoblast precursor cell line. Our data reveal that transcription of osteogenic factors (Bmp2, Alpl, and Runx2) and osteogenesis are decreased with iPLAβ-deficiency. These outcomes are corroborated and recapitulated in WT cells treated with a selective inhibitor of iPLA β (10 μM S-BEL), and rescued in iPLAβ-deficient cells by additions of 10 μM PGE. Further, under osteogenic conditions we find that PGE production is through iPLAβ activity and that this leads to induction of Runx2 and iPLAβ transcription. These findings reveal a strong link between osteogenesis and iPLAβ-derived lipids and raise the intriguing possibility that iPLAβ-derived PGE participates in osteogenesis and in the regulation of Runx2 and also iPLAβ.
Topics: Animals; Bone and Bones; Dinoprostone; Group VI Phospholipases A2; Insulin-Secreting Cells; Mice; Osteogenesis; Phospholipases A2
PubMed: 34923151
DOI: 10.1016/j.prostaglandins.2021.106605 -
Harmful and protective roles of group V phospholipase A: Current perspectives and future directions.Biochimica Et Biophysica Acta.... Jun 2019Group V Phospholipase A (Pla2g5) is a member of the PLA family of lipid-generating enzymes. It is expressed in immune and non-immune cell types and is inducible during... (Review)
Review
Group V Phospholipase A (Pla2g5) is a member of the PLA family of lipid-generating enzymes. It is expressed in immune and non-immune cell types and is inducible during several pathologic conditions serving context-specific functions. In this review, we recapitulate the protective and detrimental functions of Pla2g5 investigated through preclinical and translational approaches. This article is part of a Special Issue entitled Novel functions of phospholipase A Guest Editors: Makoto Murakami and Gerard Lambeau.
Topics: Animals; Humans; Immunity; Phospholipases A2
PubMed: 30308324
DOI: 10.1016/j.bbalip.2018.10.001