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Nicolas G. Bazan - One of the best experts on this subject based on the ideXlab platform.
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Lipid Signaling in neural plasticity, brain repair, and neuroprotection
Molecular Neurobiology, 2005Co-Authors: Nicolas G. BazanAbstract:The extensive networking of the cells of the nervous system results in large cell membrane surface areas. We now know that neuronal membranes contain phosphoLipid pools that are the reservoirs for the synthesis of specific Lipid messengers on neuronal stimulation or injury. These messengers in turn participate in Signaling cascades that can either promote neuronal injury or neuroprotection. Prostaglandins are synthesized as a result of cyclooxygenase activity. In the first step of the arachidonic acid cascade, the short-lived precursor, prostaglandin H2, is synthesized. Additional steps in the cascade result in the synthesis of an array of prostaglandins, which participate in numerous physiological and neurological processes. Our laboratory recently reported that the membrane polyunsaturated fatty acid, docosahexaenoic acid, is the precursor of oxygenation products now known as the docosanoids, some of which are powerful counter-proinflammatory mediators. The mediator 10,17S-docosatriene (neuroprotectin D1, NPD1) counteracts leukocyte infiltration, NF-κ activation, and proinflammatory gene expression in brain ischemia-reperfusion and is an apoptostatic mediator, potently counteracting oxidative stress-triggered apoptotic DNA damage in retinal pigment epithelial cells. NPD1 also upregulates the anti-apoptotic proteins Bcl-2 and Bcl-xL and decreases pro-apoptotic Bax and Bad expression. Another biologically active messenger derived from membrane phosphoLipids in response to synaptic activity is platelet-activating factor (PAF). The tight regulation of the balance between synthesis (via phospholipases) and degradation (via acetylhydrolases) of PAF modulates the functions of this Lipid messenger. Under pathological conditions, this balance is tipped, and PAF becomes a proinflammatory mediator and neurotoxic agent. The newly discovered docosahexaenoic acid Signaling pathways, as well as other Lipid messengers related to synaptic activation, may lead to the clarification of clinical issues relevant to stroke, age-related macular degeneration, spinal cord injury, Alzheimer’s disease, and other diseases that include neuroinflammatory components.
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Lipid Signaling: sleep, synaptic plasticity, and neuroprotection.
Prostaglandins & Other Lipid Mediators, 2005Co-Authors: Chu Chen, Nicolas G. BazanAbstract:Increasing evidence indicates that bioactive Lipids participate in the regulation of synaptic function and dysfunction. We have demonstrated that Signaling mediated by platelet-activating factor (PAF) and cyclooxygenase (COX)-2-synthesized PGE2 is involved in synaptic plasticity, memory, and neuronal protection [Clark GD, Happel LT, Zorumski CF, Bazan NG. Enhancement of hippocampal excitatory synaptic transmission by platelet-activating factor. Neuron 1992; 9:1211; Kato K, Clark GD, Bazan NG, Zorumski CF. Platelet-activating factor as a potential retrograde messenger in CA1 hippocampal long-term potentiation. Nature 1994; 367:175; Izquierdo I, Fin C, Schmitz PK, et al. Memory enhancement by intrahippocampal, intraamygdala or intraentorhinal infusion of platelet-activating factor measured in an inhibitory avoidance. Proc Natl Acad Sci USA 1995; 92:5047; Chen C, Magee CJ, Bazan NG. Cyclooxygenase-2 regulates prostaglandin E2 Signaling in hippocampal long-term synaptic plasticity. J Neurophysiol 2002; 87:2851]. Recently, we found that prolonged continuous wakefulness (primarily rapid eye movement (REM)-sleep deprivation, SD) causes impairments in hippocampal long-term synaptic plasticity and hippocampus-dependent memory formation [McDermott CM, LaHoste GJ, Chen C, Musto A, Bazan NG, Magee JC. Sleep deprivation causes behavioral, synaptic, and membrane excitability alterations in hippocampal neurons. J Neurosci 2003; 23:9687]. To explore the mechanisms underlying SD-induced impairments, we have studied several bioactive Lipids in the hippocampus following SD. It appears that SD causes increases in prostaglandin D2 (PGD2) and 2-arachidonylglycerol (2-AG), and a decrease in PGE2, suggesting that these Lipid messengers participate in memory consolidation during REM sleep. We have also explored the formation of endogenous neuroprotective Lipids. Toward this aim, we have used ischemia-reperfusion damage and LC-PDA-ESI-MS-MS-based Lipidomic analysis and identified docosanoids derived from synaptic phosphoLipid-enriched docosahexaenoic acid. Some of the docosanoids exert potent neuroprotective bioactivity [Marcheselli VL, Hong S, Lukiw WJ, et al. Novel docosanoids inhibit brain ischemia-reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression. J Biol Chem 2003; 278:43807; Mukherjee PK, Marcheselli VL, Serhan CN, Bazan, NG. Neuroprotectin D1: A docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress. Proc Nat Acad Sci USA 2004; 101:8491). Taken together, these observations that Signaling Lipids participate in synaptic plasticity, cognition, and survival indicate that Lipid Signaling is closely associated with several functions (e.g; learning and memory, sleep, and experimental stroke) and pathologic events. Alterations in endogenous Signaling Lipids or their receptors resulting from drug abuse lead to changes in synaptic circuitry and induce profound effects on these important functions. In the present article, we will briefly review bioactive Lipids involved in sleep, synaptic transmission and plasticity, and neuroprotection, focusing mainly on our experimental studies and how these Signaling molecules are related to functions and implicated in some neurologic disorders.
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synaptic Lipid Signaling significance of polyunsaturated fatty acids and platelet activating factor
Journal of Lipid Research, 2003Co-Authors: Nicolas G. BazanAbstract:Neuronal cellular and intracellular membranes are rich in specialized phosphoLipids that are reservoirs of Lipid messengers released by specific phospholipases and stimulated by neurotransmitters, neurotrophic factors, cytokines, membrane depolarization, ion channel activation, etc. Secretory phospholipases A2 may be both intercellular messengers and generators of Lipid messengers. The highly networked nervous system includes cells (e.g., astrocytes, oligodendrocytes, microglial cells, endothelial microvascular cells) that extensively interact with neurons; several Lipid messengers participate in these interactions. This review highlights modulation of postsynaptic membrane excitability and long-term synaptic plasticity by cyclooxygenase-2-generated prostaglandin E2, arachidonoyldiacylcylglycerol, and arachidonic acid-containing endocannabinoids. The peroxidation of docosahexaenoic acid (DHA), a critical component of excitable membranes in brain and retina, is promoted by oxidative stress. DHA is also the precursor of enzyme-derived, neuroprotective docosanoids. The phosphoLipid platelet-activating factor is a retrograde messenger of long-term potentiation, a modulator of glutamate release, and an upregulator of memory formation. Lipid messengers modulate Signaling cascades and contribute to cellular differentiation, function, protection, and repair in the nervous system. Lipidomic neurobiology will advance our knowledge of the brain, spinal cord, retina, and peripheral nerve function and diseases that affect them, and new discoveries on networks of Signaling in health and disease will likely lead to novel therapeutic interventions.
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Synaptic Lipid Signaling significance of polyunsaturated fatty acids and platelet-activating factor
Journal of Lipid Research, 2003Co-Authors: Nicolas G. BazanAbstract:Neuronal cellular and intracellular membranes are rich in specialized phosphoLipids that are reservoirs of Lipid messengers released by specific phospholipases and stimulated by neurotransmitters, neurotrophic factors, cyto- kines, membrane depolarization, ion channel activation, etc. Secretory phospholipases A 2 may be both intercellular messengers and generators of Lipid messengers. The highly networked nervous system includes cells (e.g., astrocytes, oligodendrocytes, microglial cells, endothelial microvascu- lar cells) that extensively interact with neurons; several Lipid messengers participate in these interactions. This review highlights modulation of postsynaptic membrane excitability and long-term synaptic plasticity by cyclooxygenase-2-gener- ated prostaglandin E2, arachidonoyldiacylcylglycerol, and arachidonic acid-containing endocannabinoids. The peroxi- dation of docosahexaenoic acid (DHA), a critical compo- nent of excitable membranes in brain and retina, is pro- moted by oxidative stress. DHA is also the precursor of enzyme-derived, neuroprotective docosanoids. The phos- phoLipid platelet-activating factor is a retrograde messen- ger of long-term potentiation, a modulator of glutamate re- lease, and an upregulator of memory formation. Lipid messengers modulate Signaling cascades and contribute to cellular differentiation, function, protection, and repair in the nervous system. Lipidomic neurobiology will advance our knowledge of the brain, spinal cord, retina, and periph- eral nerve function and diseases that affect them, and new discoveries on networks of Signaling in health and disease will likely lead to novel therapeutic interventions. —Bazan, N. G. Synaptic Lipid Signaling: significance of polyunsatu- rated fatty acids and platelet-activating factor. J. Lipid Res. 2003. 44: 2221-2233.
Virginie Herve - One of the best experts on this subject based on the ideXlab platform.
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Pseudomonas aeruginosa Lipoxygenase LoxA Contributes to Lung Infection by Altering the Host Immune Lipid Signaling
Frontiers in Microbiology, 2019Co-Authors: Eric Morello, Teresa Pérez-berezo, Chloé Boisseau, Thomas Baranek, Antoine Guillon, Deborah Brea, Philippe Lanotte, Xavier Carpena, Nicolas Pietrancosta, Virginie HerveAbstract:Pseudomonas aeruginosa is an opportunistic bacteria and a major cause of nosocomial pneumonia. P. aeruginosa has many virulence factors contributing to its ability to colonize the host. LoxA is a lipoxygenase enzyme secreted by P. aeruginosa that oxidizes polyunsaturated fatty acids. Based on previous in vitro biochemical studies, several biological roles of LoxA have been hypothesized, including interference of the host Lipid Signaling, and modulation of bacterial invasion properties. However, the contribution of LoxA to P. aeruginosa lung pathogenesis per se remained unclear. In this study, we used complementary in vitro and in vivo approaches, clinical strains of P. aeruginosa as well as Lipidomics technology to investigate the role of LoxA in lung infection. We found that several P. aeruginosa clinical isolates express LoxA. When secreted in the lungs, LoxA processes a wide range of host polyunsaturated fatty acids, which further results in the production of bioactive Lipid mediators (including lipoxin A(4)). LoxA also inhibits the expression of major chemokines (e.g., MIPs and KC) and the recruitment of key leukocytes. Remarkably, LoxA promotes P. aeruginosa persistence in lungs tissues. Hence, our study suggests that LoxA-dependent interference of the host Lipid pathways may contribute to P. aeruginosa lung pathogenesis.
Vytas A. Bankaitis - One of the best experts on this subject based on the ideXlab platform.
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The Sec14 superfamily and mechanisms for crosstalk between Lipid metabolism and Lipid Signaling
Trends in Biochemical Sciences, 2010Co-Authors: Vytas A. Bankaitis, Carl J. Mousley, Gabriel SchaafAbstract:Lipid Signaling pathways define central mechanisms for cellular regulation. Productive Lipid Signaling requires an orchestrated coupling between Lipid metabolism, Lipid organization and the action of protein machines that execute appropriate downstream reactions. Using membrane trafficking control as primary context, we explore the idea that the Sec14-protein superfamily defines a set of modules engineered for the sensing of specific aspects of Lipid metabolism and subsequent transduction of ‘sensing’ information to a phosphoinositide-driven ‘execution phase’. In this manner, the Sec14 superfamily connects diverse territories of the Lipid metabolome with phosphoinositide Signaling in a productive ‘crosstalk’ between these two systems. Mechanisms of crosstalk, by which non-enzymatic proteins integrate metabolic cues with the action of interfacial enzymes, represent unappreciated regulatory themes in Lipid Signaling.
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Phosphatidylinositol transfer proteins and functional specification of Lipid Signaling pools.
Advances in Enzyme Regulation, 2007Co-Authors: Vytas A. Bankaitis, Patrick Vincent, Maria Merkulova, Kim Tyeryar, Yang LiuAbstract:The diversity of Lipid species in biological membranes testifies to the multiple roles of these molecules as structural units, precursors to second messengers, as scaffolding units that impose spatial and temporal regulation on assembly of proteins, and as regulators of the catalytic activities of proteins. Such diverse Lipid functions must be appropriately coordinated so that these can be specifically and appropriately coupled to dedicated biological processes. Evidence from multiple sources is building towards a concept where Sec14-like PITPs are specific components of Lipid metabolic nanoreactors and, in this capacity, help impose a functional specification of Lipid Signaling pools.
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Phosphatidylinositol transfer proteins and cellular nanoreactors for Lipid Signaling
Nature Chemical Biology, 2006Co-Authors: Gabriel Schaaf, Vytas A. BankaitisAbstract:Membrane Lipids function as structural molecules, reservoirs for second messengers, membrane platforms that scaffold protein assembly and regulators of enzymes and ion channels. Such diverse Lipid functions contribute substantially to cellular mechanisms for fine-tuning membrane-Signaling events. Meaningful coordination of these events requires exquisite spatial and temporal control of Lipid metabolism and organization, and reliable mechanisms for specifically coupling these parameters to dedicated physiological processes. Recent studies suggest such integration is linked to the action of phosphatidylinositol transfer proteins that operate at the interface of the metabolism, trafficking and organization of specific Lipids.
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the yeast and mammalian isoforms of phosphatidylinositol transfer protein can all restore phospholipase c mediated inositol Lipid Signaling in cytosol depleted rbl 2h3 and hl 60 cells
Proceedings of the National Academy of Sciences of the United States of America, 1996Co-Authors: Emer Cunningham, Vytas A. Bankaitis, Siow Khoon Tan, Philip Swigart, Justin J Hsuan, Shamshad CockcroftAbstract:Abstract The mammalian phosphatidylinositol transfer proteins (PITP) and the yeast Saccharomyces cerevisiae PITP (SEC14p) that show no sequence homology both catalyze exchange of phosphatidylinositol (PI) between membranes compartments in vitro. In HL-60 cells where the cytosolic proteins are depleted by permeabilization, exogenously added PITPalpha is required to restore G protein-mediated phospholipase Cbeta (PLCbeta) Signaling. Recently, a second mammalian PITPbeta form has been described that shows 77% identity to rat PITPalpha. We have examined the ability of the two mammalian PITPs and SEC14p to restore PLC-mediated Signaling in cytosol-depleted HL-60 and RBL-2H3 cells. Both PITPalpha and PITPbeta isoforms as well as SEC14p restore G protein-mediated PLCbeta Signaling with a similar potency. In RBL-2H3 cells, crosslinking of the IgE receptor by antigen stimulates inositol Lipid hydrolysis by tyrosine phosphorylation of PLCgamma1. Permeabilization of RBL cells leads to loss of PLCgamma1 as well as PITP into the extracellular medium and this coincides with loss of antigen-stimulated Lipid hydrolysis. Both PLCgamma1 and PITP were required to restore inositol Lipid Signaling. We conclude that (i) because the PI binding/transfer activities of PITP/SEC14p is the common feature shared by all three transfer proteins, it must be the relevant activity that determines their abilities to restore inositol Lipid-mediated Signaling and (ii) PITP is a general requirement for inositol Lipid hydrolysis regardless of how and which isoform of PLC is activated by the appropriate agonist.
Chu Chen - One of the best experts on this subject based on the ideXlab platform.
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Lipid Signaling and Synaptic Plasticity
The Neuroscientist, 2006Co-Authors: Nan Sang, Chu ChenAbstract:Lipids are essential components of plasma- and organelle-membranes, not only providing a frame for embedded proteins (e.g., receptors and ion channels) but also functioning as reservoirs for Lipid mediators. Increasing evidence indicates that bioactive Lipids such as eicosanoids, endocannabinoids, and lysophosphoLipids serve as intercellular and intracellular Signaling molecules participating in physiological and pathological functions in the brain. The discovery of some of these Lipid receptors and novel Lipid Signaling mediators has sparked an intense interest in Lipidomic neurobiology research. Classic prostaglandins (PGD2, PGE2, PGF2α, PGI2, and TXA2), catalyzed by cyclooxygenases (COX), are synthesized from arachidonic acid (AA). Experimental studies demonstrate that prostaglandin E2 (PGE2), mainly derived from the COX-2 reaction, is an important mediator, acting as a retrograde messenger via a presynaptic PGE2 subtype 2 receptor (EP2) in modulation of synaptic events. Novel prostaglandins (prostagla...
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Lipid Signaling and Synaptic Plasticity
The Neuroscientist : a review journal bringing neurobiology neurology and psychiatry, 2006Co-Authors: Nan Sang, Chu ChenAbstract:Lipids are essential components of plasma- and organelle-membranes, not only providing a frame for embedded proteins (e.g., receptors and ion channels) but also functioning as reservoirs for Lipid mediators. Increasing evidence indicates that bioactive Lipids such as eicosanoids, endocannabinoids, and lysophosphoLipids serve as intercellular and intracellular Signaling molecules participating in physiological and pathological functions in the brain. The discovery of some of these Lipid receptors and novel Lipid Signaling mediators has sparked an intense interest in Lipidomic neurobiology research. Classic prostaglandins (PGD(2), PGE(2), PGF(2alpha), PGI(2), and TXA(2)), catalyzed by cyclooxygenases (COX), are synthesized from arachidonic acid (AA). Experimental studies demonstrate that prostaglandin E(2) (PGE(2)), mainly derived from the COX-2 reaction, is an important mediator, acting as a retrograde messenger via a presynaptic PGE(2) subtype 2 receptor (EP(2)) in modulation of synaptic events. Novel prostaglandins (prostaglandin glycerol esters and prostaglandin ethanolamides) are COX-2 oxidative metabolites of endogenous cannabinoids (2-arachidonyl glycerol and arachidonyl ethanolamide). Recent evidence suggests that these new types of prostaglandins are likely novel Signaling mediators involved in synaptic transmission and plasticity. This means that COX- 2 plays a central role in metabolisms of AA and endocannabinoids (eCBs) and productions of AA- and eCB- derived prostaglandins. Thus, in the present review article, the authors will mainly discuss COX-2 regulation of prostaglandin Signaling in modulation of hippocampal synaptic transmission and plasticity.
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Lipid Signaling: sleep, synaptic plasticity, and neuroprotection.
Prostaglandins & Other Lipid Mediators, 2005Co-Authors: Chu Chen, Nicolas G. BazanAbstract:Increasing evidence indicates that bioactive Lipids participate in the regulation of synaptic function and dysfunction. We have demonstrated that Signaling mediated by platelet-activating factor (PAF) and cyclooxygenase (COX)-2-synthesized PGE2 is involved in synaptic plasticity, memory, and neuronal protection [Clark GD, Happel LT, Zorumski CF, Bazan NG. Enhancement of hippocampal excitatory synaptic transmission by platelet-activating factor. Neuron 1992; 9:1211; Kato K, Clark GD, Bazan NG, Zorumski CF. Platelet-activating factor as a potential retrograde messenger in CA1 hippocampal long-term potentiation. Nature 1994; 367:175; Izquierdo I, Fin C, Schmitz PK, et al. Memory enhancement by intrahippocampal, intraamygdala or intraentorhinal infusion of platelet-activating factor measured in an inhibitory avoidance. Proc Natl Acad Sci USA 1995; 92:5047; Chen C, Magee CJ, Bazan NG. Cyclooxygenase-2 regulates prostaglandin E2 Signaling in hippocampal long-term synaptic plasticity. J Neurophysiol 2002; 87:2851]. Recently, we found that prolonged continuous wakefulness (primarily rapid eye movement (REM)-sleep deprivation, SD) causes impairments in hippocampal long-term synaptic plasticity and hippocampus-dependent memory formation [McDermott CM, LaHoste GJ, Chen C, Musto A, Bazan NG, Magee JC. Sleep deprivation causes behavioral, synaptic, and membrane excitability alterations in hippocampal neurons. J Neurosci 2003; 23:9687]. To explore the mechanisms underlying SD-induced impairments, we have studied several bioactive Lipids in the hippocampus following SD. It appears that SD causes increases in prostaglandin D2 (PGD2) and 2-arachidonylglycerol (2-AG), and a decrease in PGE2, suggesting that these Lipid messengers participate in memory consolidation during REM sleep. We have also explored the formation of endogenous neuroprotective Lipids. Toward this aim, we have used ischemia-reperfusion damage and LC-PDA-ESI-MS-MS-based Lipidomic analysis and identified docosanoids derived from synaptic phosphoLipid-enriched docosahexaenoic acid. Some of the docosanoids exert potent neuroprotective bioactivity [Marcheselli VL, Hong S, Lukiw WJ, et al. Novel docosanoids inhibit brain ischemia-reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression. J Biol Chem 2003; 278:43807; Mukherjee PK, Marcheselli VL, Serhan CN, Bazan, NG. Neuroprotectin D1: A docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress. Proc Nat Acad Sci USA 2004; 101:8491). Taken together, these observations that Signaling Lipids participate in synaptic plasticity, cognition, and survival indicate that Lipid Signaling is closely associated with several functions (e.g; learning and memory, sleep, and experimental stroke) and pathologic events. Alterations in endogenous Signaling Lipids or their receptors resulting from drug abuse lead to changes in synaptic circuitry and induce profound effects on these important functions. In the present article, we will briefly review bioactive Lipids involved in sleep, synaptic transmission and plasticity, and neuroprotection, focusing mainly on our experimental studies and how these Signaling molecules are related to functions and implicated in some neurologic disorders.
Eric Morello - One of the best experts on this subject based on the ideXlab platform.
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Pseudomonas aeruginosa Lipoxygenase LoxA Contributes to Lung Infection by Altering the Host Immune Lipid Signaling
Frontiers in Microbiology, 2019Co-Authors: Eric Morello, Teresa Pérez-berezo, Chloé Boisseau, Thomas Baranek, Antoine Guillon, Deborah Brea, Philippe Lanotte, Xavier Carpena, Nicolas Pietrancosta, Virginie HerveAbstract:Pseudomonas aeruginosa is an opportunistic bacteria and a major cause of nosocomial pneumonia. P. aeruginosa has many virulence factors contributing to its ability to colonize the host. LoxA is a lipoxygenase enzyme secreted by P. aeruginosa that oxidizes polyunsaturated fatty acids. Based on previous in vitro biochemical studies, several biological roles of LoxA have been hypothesized, including interference of the host Lipid Signaling, and modulation of bacterial invasion properties. However, the contribution of LoxA to P. aeruginosa lung pathogenesis per se remained unclear. In this study, we used complementary in vitro and in vivo approaches, clinical strains of P. aeruginosa as well as Lipidomics technology to investigate the role of LoxA in lung infection. We found that several P. aeruginosa clinical isolates express LoxA. When secreted in the lungs, LoxA processes a wide range of host polyunsaturated fatty acids, which further results in the production of bioactive Lipid mediators (including lipoxin A(4)). LoxA also inhibits the expression of major chemokines (e.g., MIPs and KC) and the recruitment of key leukocytes. Remarkably, LoxA promotes P. aeruginosa persistence in lungs tissues. Hence, our study suggests that LoxA-dependent interference of the host Lipid pathways may contribute to P. aeruginosa lung pathogenesis.