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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 -
Journal of Neurochemistry May 2020Despite the human brain being made of nearly 60% fat, the vast majority of studies on the mechanisms of neuronal communication which underpin cognition, memory and... (Review)
Review
Despite the human brain being made of nearly 60% fat, the vast majority of studies on the mechanisms of neuronal communication which underpin cognition, memory and learning, primarily focus on proteins and/or (epi)genetic mechanisms. Phospholipids are the main component of all cellular membranes and function as substrates for numerous phospholipid-modifying enzymes, including phospholipases, which release free fatty acids (FFAs) and other lipid metabolites that can alter the intrinsic properties of the membranes, recruit and activate critical proteins, and act as lipid signalling molecules. Here, we will review brain specific phospholipases, their roles in membrane remodelling, neuronal function, learning and memory, as well as their disease implications. In particular, we will highlight key roles of unsaturated FFAs, particularly arachidonic acid, in neurotransmitter release, neuroinflammation and memory. In light of recent findings, we will also discuss the emerging role of phospholipase A and the creation of saturated FFAs in the brain.
Topics: Animals; Brain; Humans; Learning; Memory; Neurons; Phospholipases; Phospholipids
PubMed: 31745996
DOI: 10.1111/jnc.14918 -
Neuroscience and Biobehavioral Reviews Sep 2021Chronic systemic inflammation is associated with an increased risk of cardiovascular disease in an environment of low low-density lipoprotein (LDL) and low total... (Review)
Review
Chronic systemic inflammation is associated with an increased risk of cardiovascular disease in an environment of low low-density lipoprotein (LDL) and low total cholesterol and with the pathophysiology of neuroprogressive disorders. The causes and consequences of this lipid paradox are explored. Circulating activated neutrophils can release inflammatory molecules such as myeloperoxidase and the pro-inflammatory cytokines interleukin-1 beta, interleukin-6 and tumour necrosis factor-alpha. Since activated neutrophils are associated with atherosclerosis and cardiovascular disease and with major depressive disorder, bipolar disorder and schizophrenia, it seems reasonable to hypothesise that the inflammatory molecules released by them may act as mediators of the link between systemic inflammation and the development of atherosclerosis in neuroprogressive disorders. This hypothesis is tested by considering the association at a molecular level of systemic inflammation with increased LDL oxidation; increased small dense LDL levels; increased lipoprotein (a) concentration; secretory phospholipase A activation; cytosolic phospholipase A activation; increased platelet activation; decreased apolipoprotein A1 levels and function; decreased paroxonase-1 activity; hyperhomocysteinaemia; and metabolic endotoxaemia. These molecular mechanisms suggest potential therapeutic targets.
Topics: Atherosclerosis; Cytokines; Humans; Inflammation; Lipids; Lipoproteins, LDL; Neurodegenerative Diseases; Neutrophils; Peroxidase; Phospholipases A2
PubMed: 34118292
DOI: 10.1016/j.neubiorev.2021.06.017 -
Toxicon : Official Journal of the... Sep 2023Research on centipede venoms has led to the discovery of a diverse array of novel proteins and peptides, including those with homology to previously discovered toxin...
Research on centipede venoms has led to the discovery of a diverse array of novel proteins and peptides, including those with homology to previously discovered toxin families (e.g., phospholipase A2s and pM12a metalloproteases) and novel toxin families not previously detected in venoms (e.g., β-pore forming toxins and scoloptoxins). Most of this research has focused on centipedes in the order Scolopendromorpha, particularly those in the families Scolopendridae, Cryptopidae, and Scolopocryptopidae. To generate the first high-throughput venom characterization for a centipede in the scolopendromorph family Plutoniumidae, we performed venom-gland transcriptomics and venom proteomics on two Theatops posticus. We identified a total of 64 venom toxins, 60 of which were detected in both the venom-gland transcriptome and venom proteome and four of which were only detected transcriptomically. We detected a single highly abundant arylsulfatase B (ARSB) toxin, the first ARSB toxin identified from centipede venoms. As ARSBs have been detected in other venomous species (e.g., scorpions), ARSBs in T. posticus highlights a new case of convergent evolution across venoms. Theatops posticus venom also contained a much higher abundance and diversity of phospholipase A2 toxins compared to other characterized centipede venoms. Conversely, we detected other common centipedes toxins, such as CAPs and scoloptoxins, at relatively low abundances and diversities. Our observation of a diverse set of toxins from T. posticus venom, including those from novel toxin families, emphasizes the importance of studying unexplored centipede taxonomic groups and the continued potential of centipede venoms for novel toxin discovery and unraveling the molecular mechanisms underlying trait evolution.
Topics: Animals; Chilopoda; Arthropods; Arylsulfatases; Phospholipases; Arthropod Venoms; Transcriptome
PubMed: 37517595
DOI: 10.1016/j.toxicon.2023.107231 -
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 -
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 -
Journal of Leukocyte Biology Jul 2023The current dogma is that chemoattractants G protein-coupled receptors activate β phospholipase C while receptor tyrosine kinases activate γ phospholipase C. Here, we...
The current dogma is that chemoattractants G protein-coupled receptors activate β phospholipase C while receptor tyrosine kinases activate γ phospholipase C. Here, we show that chemoattractant/G protein-coupled receptor-mediated membrane recruitment of γ2 phospholipase C constitutes G protein-coupled receptor-mediated phospholipase C signaling and is essential for neutrophil polarization and migration during chemotaxis. In response to a chemoattractant stimulation, cells lacking γ2 phospholipase C (plcg2kd) displayed altered dynamics of diacylglycerol production and calcium response, increased Ras/PI3K/Akt activation, elevated GSK3 phosphorylation and cofilin activation, impaired dynamics of actin polymerization, and, consequently, defects in cell polarization and migration during chemotaxis. The study reveals a molecular mechanism of membrane targeting of γ2 phospholipase C and the signaling pathways by which γ2 phospholipase C plays an essential role in neutrophil chemotaxis.
Topics: Chemotaxis; Neutrophils; Phosphatidylinositol 3-Kinases; Phospholipase C gamma; Glycogen Synthase Kinase 3; Receptors, G-Protein-Coupled; Chemotactic Factors; Type C Phospholipases
PubMed: 37040618
DOI: 10.1093/jleuko/qiad043 -
Plant Physiology and Biochemistry : PPB Jan 2022Phospholipase Ds (PLDs) are a heterogeneous group of enzymes that are widely distributed in organisms. These enzymes hydrolyze the structural phospholipids of the plasma... (Review)
Review
Phospholipase Ds (PLDs) are a heterogeneous group of enzymes that are widely distributed in organisms. These enzymes hydrolyze the structural phospholipids of the plasma membrane, releasing phosphatidic acid (PA), an important secondary messenger. Plant PLDs play essential roles in several biological processes, including growth and development, abiotic stress responses, and plant-microbe interactions. Although the roles of PLDs in plant-pathogen interactions have been extensively studied, their roles in symbiotic relationships are not well understood. The establishment of the best-studied symbiotic interactions, those between legumes and rhizobia and between most plants and mycorrhizae, requires the regulation of several physiological, cellular, and molecular processes. The roles of PLDs in hormonal signaling, lipid metabolism, and cytoskeletal dynamics during rhizobial symbiosis were recently explored. However, to date, the roles of PLDs in mycorrhizal symbiosis have not been reported. Here, we present a critical review of the participation of PLDs in the interactions of plants with pathogens, nitrogen-fixing bacteria, and arbuscular mycorrhizal fungi. We describe how PLDs regulate rhizobial and mycorrhizal symbiosis by modulating reactive oxygen species levels, hormonal signaling, cytoskeletal rearrangements, and G-protein activity.
Topics: Mycorrhizae; Phospholipase D; Phospholipases; Plants; Symbiosis
PubMed: 35101797
DOI: 10.1016/j.plaphy.2022.01.025