The Experts below are selected from a list of 129 Experts worldwide ranked by ideXlab platform
Ramon Trullas - One of the best experts on this subject based on the ideXlab platform.
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nmda receptor overactivation inhibits phospholipid synthesis by decreasing choline Ethanolamine Phosphotransferase activity
The Journal of Neuroscience, 2003Co-Authors: Teresa Gasull, Elisabet Sarri, Nuria Degregoriorocasolano, Ramon TrullasAbstract:Overactivation of NMDA receptors is believed to induce neuronal death by increasing phospholipid hydrolysis and subsequent degradation. We showed previously that NMDA releases choline and inhibits incorporation of [ 3 H]choline into phosphatidylcholine before excitotoxic neuronal death. On the basis of these results, we hypothesized that excitotoxicity results from inhibition of synthesis rather than from increased degradation of phospholipids. We now investigated the effect of NMDA receptor overactivation on synthesis and degradation of major membrane phospholipids in the early stages of the excitotoxic process. Exposure of cortical neurons to neurotoxic concentrations of NMDA increased extracellular choline and activated hydrolysis of phosphatidylcholine and phosphatidylinositol by phospholipase A 2 but did not induce significant degradation of phosphatidylcholine, phosphatidylinositol, phosphatidylEthanolamine, or phosphatidylserine. In contrast, NMDA strongly reduced the incorporation of [ 3 H]choline and [ 3 H]Ethanolamine into their respective phospholipids. Metabolic labeling experiments in whole cells showed that NMDA receptor overactivation does not modify the activity of phosphocholine or phosphoEthanolamine cytidylyltransferases but strongly inhibits choline–Ethanolamine Phosphotransferase activity. This effect was observed well before any significant membrane damage and cell death. Moreover, cholinePhosphotransferase activity was lower in microsomes from NMDA-treated cells. These results show that membrane damage by NMDA is preceded by inhibition of phospholipid synthesis and not by phospholipid degradation in the early stages of the excitotoxic process, and that NMDA receptor overactivation decreases phosphatidylcholine and phosphatidylEthanolamine synthesis by inhibiting choline–ethanolaminoPhosphotransferase activity.
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NMDA Receptor Overactivation Inhibits Phospholipid Synthesis by Decreasing Choline–Ethanolamine Phosphotransferase Activity
The Journal of Neuroscience, 2003Co-Authors: Teresa Gasull, Elisabet Sarri, Nuria Degregorio-rocasolano, Ramon TrullasAbstract:Overactivation of NMDA receptors is believed to induce neuronal death by increasing phospholipid hydrolysis and subsequent degradation. We showed previously that NMDA releases choline and inhibits incorporation of [ 3 H]choline into phosphatidylcholine before excitotoxic neuronal death. On the basis of these results, we hypothesized that excitotoxicity results from inhibition of synthesis rather than from increased degradation of phospholipids. We now investigated the effect of NMDA receptor overactivation on synthesis and degradation of major membrane phospholipids in the early stages of the excitotoxic process. Exposure of cortical neurons to neurotoxic concentrations of NMDA increased extracellular choline and activated hydrolysis of phosphatidylcholine and phosphatidylinositol by phospholipase A 2 but did not induce significant degradation of phosphatidylcholine, phosphatidylinositol, phosphatidylEthanolamine, or phosphatidylserine. In contrast, NMDA strongly reduced the incorporation of [ 3 H]choline and [ 3 H]Ethanolamine into their respective phospholipids. Metabolic labeling experiments in whole cells showed that NMDA receptor overactivation does not modify the activity of phosphocholine or phosphoEthanolamine cytidylyltransferases but strongly inhibits choline–Ethanolamine Phosphotransferase activity. This effect was observed well before any significant membrane damage and cell death. Moreover, cholinePhosphotransferase activity was lower in microsomes from NMDA-treated cells. These results show that membrane damage by NMDA is preceded by inhibition of phospholipid synthesis and not by phospholipid degradation in the early stages of the excitotoxic process, and that NMDA receptor overactivation decreases phosphatidylcholine and phosphatidylEthanolamine synthesis by inhibiting choline–ethanolaminoPhosphotransferase activity.
Teresa Gasull - One of the best experts on this subject based on the ideXlab platform.
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nmda receptor overactivation inhibits phospholipid synthesis by decreasing choline Ethanolamine Phosphotransferase activity
The Journal of Neuroscience, 2003Co-Authors: Teresa Gasull, Elisabet Sarri, Nuria Degregoriorocasolano, Ramon TrullasAbstract:Overactivation of NMDA receptors is believed to induce neuronal death by increasing phospholipid hydrolysis and subsequent degradation. We showed previously that NMDA releases choline and inhibits incorporation of [ 3 H]choline into phosphatidylcholine before excitotoxic neuronal death. On the basis of these results, we hypothesized that excitotoxicity results from inhibition of synthesis rather than from increased degradation of phospholipids. We now investigated the effect of NMDA receptor overactivation on synthesis and degradation of major membrane phospholipids in the early stages of the excitotoxic process. Exposure of cortical neurons to neurotoxic concentrations of NMDA increased extracellular choline and activated hydrolysis of phosphatidylcholine and phosphatidylinositol by phospholipase A 2 but did not induce significant degradation of phosphatidylcholine, phosphatidylinositol, phosphatidylEthanolamine, or phosphatidylserine. In contrast, NMDA strongly reduced the incorporation of [ 3 H]choline and [ 3 H]Ethanolamine into their respective phospholipids. Metabolic labeling experiments in whole cells showed that NMDA receptor overactivation does not modify the activity of phosphocholine or phosphoEthanolamine cytidylyltransferases but strongly inhibits choline–Ethanolamine Phosphotransferase activity. This effect was observed well before any significant membrane damage and cell death. Moreover, cholinePhosphotransferase activity was lower in microsomes from NMDA-treated cells. These results show that membrane damage by NMDA is preceded by inhibition of phospholipid synthesis and not by phospholipid degradation in the early stages of the excitotoxic process, and that NMDA receptor overactivation decreases phosphatidylcholine and phosphatidylEthanolamine synthesis by inhibiting choline–ethanolaminoPhosphotransferase activity.
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NMDA Receptor Overactivation Inhibits Phospholipid Synthesis by Decreasing Choline–Ethanolamine Phosphotransferase Activity
The Journal of Neuroscience, 2003Co-Authors: Teresa Gasull, Elisabet Sarri, Nuria Degregorio-rocasolano, Ramon TrullasAbstract:Overactivation of NMDA receptors is believed to induce neuronal death by increasing phospholipid hydrolysis and subsequent degradation. We showed previously that NMDA releases choline and inhibits incorporation of [ 3 H]choline into phosphatidylcholine before excitotoxic neuronal death. On the basis of these results, we hypothesized that excitotoxicity results from inhibition of synthesis rather than from increased degradation of phospholipids. We now investigated the effect of NMDA receptor overactivation on synthesis and degradation of major membrane phospholipids in the early stages of the excitotoxic process. Exposure of cortical neurons to neurotoxic concentrations of NMDA increased extracellular choline and activated hydrolysis of phosphatidylcholine and phosphatidylinositol by phospholipase A 2 but did not induce significant degradation of phosphatidylcholine, phosphatidylinositol, phosphatidylEthanolamine, or phosphatidylserine. In contrast, NMDA strongly reduced the incorporation of [ 3 H]choline and [ 3 H]Ethanolamine into their respective phospholipids. Metabolic labeling experiments in whole cells showed that NMDA receptor overactivation does not modify the activity of phosphocholine or phosphoEthanolamine cytidylyltransferases but strongly inhibits choline–Ethanolamine Phosphotransferase activity. This effect was observed well before any significant membrane damage and cell death. Moreover, cholinePhosphotransferase activity was lower in microsomes from NMDA-treated cells. These results show that membrane damage by NMDA is preceded by inhibition of phospholipid synthesis and not by phospholipid degradation in the early stages of the excitotoxic process, and that NMDA receptor overactivation decreases phosphatidylcholine and phosphatidylEthanolamine synthesis by inhibiting choline–ethanolaminoPhosphotransferase activity.
David A Ford - One of the best experts on this subject based on the ideXlab platform.
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separate myocardial Ethanolamine Phosphotransferase activities responsible for plasmenylEthanolamine and phosphatidylEthanolamine synthesis
Journal of Lipid Research, 2003Co-Authors: David A FordAbstract:Ethanolamine Phosphotransferase (EPT) is a key enzyme responsible for the synthesis of Ethanolamine glycerophospholipids. PlasmenylEthanolamine is a predominant molecular subclass of Ethanolamine glycerophospholipids in the heart. The present study was designed to identify the selective use of 1-O-alk-1'-enyl-2-acyl-sn-glycerol as a substrate for EPT as a mechanism responsible for the predominance of plasmenylEthanolamine in the rabbit heart. EPT activity in rabbit myocardial membranes using 1,2-diacyl-sn-glycerol as substrate is activated by Mn 2 + , inhibited by dithiobisnitrobenzoic acid (DTNB) and is unaffected by Ca 2 + . In contrast, Ethanolamine Phosphotransferase activity using 1-O-alk-1'-enyl-2-acyl-sn-glycerol as substrate is inhibited by Mn 2 + and Ca 2 + , but is activated by DTNB. Additionally, Ethanolamine Phosphotransferase activity using 1-O-alk-1'-enyl-2-acyl-sn-glycerol substrate was more sensitive to thermal denaturation compared with that of 1,2-diacyl-sn-glycerol. Taken together, these results suggest that separate Ethanolamine Phosphotransferase activities are present in heart membranes that are responsible for the synthesis of phosphatidylEthanolamine and plasmenylEthanolamine.
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the primary determinant of rabbit myocardial Ethanolamine Phosphotransferase substrate selectivity is the covalent nature of the sn 1 aliphatic group of diradyl glycerol acceptors
Journal of Biological Chemistry, 1992Co-Authors: David A Ford, K B Rosenbloom, Richard W GrossAbstract:Abstract PlasmenylEthanolamines represent the major endogenous phospholipid storage depot of arachidonic acid in many mammalian cells. To elucidate the biochemical mechanisms contributing to the high plasmalogen content and arachidonic acid enrichment present in myocardial Ethanolamine glycerophospholipids, the substrate specificity of rabbit myocardial Ethanolamine Phosphotransferase (EPT) was quantified utilizing multiple molecular species of each subclass of diradyl glycerol substrate. Myocardial EPT demonstrated over a 16-fold selectivity for 1-O-alk-1'-enyl-2-acyl-sn-glycerol (AAG) compared to 1,2-diacyl-sn-glycerol (DAG) substrate utilizing individual molecular species of each subclass dispersed in Tween 20. The selective utilization of AAG by EPT was substantiated utilizing two independent assay systems which employed either the presentation of substrate to enzyme as a substitutional impurity in Triton X-100 mixed micelles or the obligatory utilization of endogenously generated diradyl glycerol substrates. Although rabbit myocardial microsomes contained over a 20-fold molar excess of endogenous DAG to AAG mass, incubation of rabbit myocardial microsomes with CDP-Ethanolamine resulted in the highly selective synthesis of plasmenylEthanolamines which were predominantly comprised of molecular species containing arachidonic acid at the sn-2 position (greater than 75%). Endogenous AAG molecular species in rabbit myocardial microsomes were similarly enriched in arachidonic acid, and the distribution of AAG molecular species closely paralleled the distribution of plasmenylEthanolamine (but not plasmenylcholine) molecular species. Thus, the subclass and molecular species distribution of the Ethanolamine glycerophospholipids synthesized by rabbit myocardial EPT reflects independent contributions from the subclass selectivity of EPT for AAG substrate in conjunction with the enrichment of arachidonic acid in microsomal AAG molecular species.
Ryozo Imai - One of the best experts on this subject based on the ideXlab platform.
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Specific induction of TaAAPT1, an ER- and Golgi-localized ECPT-type aminoalcoholPhosphotransferase, results in preferential accumulation of the phosphatidylEthanolamine membrane phospholipid during cold acclimation in wheat
Plant Molecular Biology, 2010Co-Authors: Keita Sutoh, Nobuya Sanuki, Takeshi Sakaki, Ryozo ImaiAbstract:Cold acclimation requires substantial alteration in membrane property. In contrast to well-documented fatty acid unsaturation during cold acclimation, changes in phospholipid biosynthesis during cold acclimation are less understood. Here, we isolated and characterized two aminoalcoholPhosphotransferase (AAPT) cDNAs, TaAAPT1 and TaAAPT2 , from wheat. AAPTs utilize diacylglycerols and CDP-choline/Ethanolamine as substrates and catalyze the final step of the CDP-choline/Ethanolamine pathway for phosphatidylcholine (PC)/phosphatidylEthanolamine (PE) synthesis, respectively. Functionality of TaAAPT1 and TaAAPT2 was demonstrated by heterologous expression in a yeast cpt1Δ ept1Δ double mutant that lacks both AAPT activities. Detailed characterization of AAPT activities from the transformed mutant cells indicated that TaAAPT1 is an ECPT-type enzyme with higher Ethanolamine Phosphotransferase (EPT) activity than choline Phosphotransferase (CPT) activity, while TaAAPT2 is a CEPT-type with the opposite substrate preference. Transient expression of GFP-fused TaAAPT1 and TaAAPT2 proteins in wheat and onion cells indicated they are localized to both the endoplasmic reticulum and Golgi apparatus, suggesting that the final synthesis of PE and PC via the CDP-choline/Ethanolamine pathway occurs in these organella. Quantitative PCR analyses revealed that TaAAPT1 expression is strongly induced by cold, while TaAAPT2 was constitutively expressed at lower levels. Measurement of phospholipid content in wheat leaves indicated that PE is more prominently increased in response to cold than PC and accordingly PE/PC ratio increased from 0.385 to 0.530 during 14 days of cold acclimation. Together, these data suggested that an increase in the PE/PC ratio during cold acclimation is regulated at the final step of the biosynthetic pathway.
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Specific induction of TaAAPT1, an ER- and Golgi-localized ECPT-type aminoalcoholPhosphotransferase, results in preferential accumulation of the phosphatidylEthanolamine membrane phospholipid during cold acclimation in wheat.
Plant molecular biology, 2009Co-Authors: Keita Sutoh, Nobuya Sanuki, Takeshi Sakaki, Ryozo ImaiAbstract:Cold acclimation requires substantial alteration in membrane property. In contrast to well-documented fatty acid unsaturation during cold acclimation, changes in phospholipid biosynthesis during cold acclimation are less understood. Here, we isolated and characterized two aminoalcoholPhosphotransferase (AAPT) cDNAs, TaAAPT1 and TaAAPT2, from wheat. AAPTs utilize diacylglycerols and CDP-choline/Ethanolamine as substrates and catalyze the final step of the CDP-choline/Ethanolamine pathway for phosphatidylcholine (PC)/phosphatidylEthanolamine (PE) synthesis, respectively. Functionality of TaAAPT1 and TaAAPT2 was demonstrated by heterologous expression in a yeast cpt1Delta ept1Delta double mutant that lacks both AAPT activities. Detailed characterization of AAPT activities from the transformed mutant cells indicated that TaAAPT1 is an ECPT-type enzyme with higher Ethanolamine Phosphotransferase (EPT) activity than choline Phosphotransferase (CPT) activity, while TaAAPT2 is a CEPT-type with the opposite substrate preference. Transient expression of GFP-fused TaAAPT1 and TaAAPT2 proteins in wheat and onion cells indicated they are localized to both the endoplasmic reticulum and Golgi apparatus, suggesting that the final synthesis of PE and PC via the CDP-choline/Ethanolamine pathway occurs in these organella. Quantitative PCR analyses revealed that TaAAPT1 expression is strongly induced by cold, while TaAAPT2 was constitutively expressed at lower levels. Measurement of phospholipid content in wheat leaves indicated that PE is more prominently increased in response to cold than PC and accordingly PE/PC ratio increased from 0.385 to 0.530 during 14 days of cold acclimation. Together, these data suggested that an increase in the PE/PC ratio during cold acclimation is regulated at the final step of the biosynthetic pathway.
Elisabet Sarri - One of the best experts on this subject based on the ideXlab platform.
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nmda receptor overactivation inhibits phospholipid synthesis by decreasing choline Ethanolamine Phosphotransferase activity
The Journal of Neuroscience, 2003Co-Authors: Teresa Gasull, Elisabet Sarri, Nuria Degregoriorocasolano, Ramon TrullasAbstract:Overactivation of NMDA receptors is believed to induce neuronal death by increasing phospholipid hydrolysis and subsequent degradation. We showed previously that NMDA releases choline and inhibits incorporation of [ 3 H]choline into phosphatidylcholine before excitotoxic neuronal death. On the basis of these results, we hypothesized that excitotoxicity results from inhibition of synthesis rather than from increased degradation of phospholipids. We now investigated the effect of NMDA receptor overactivation on synthesis and degradation of major membrane phospholipids in the early stages of the excitotoxic process. Exposure of cortical neurons to neurotoxic concentrations of NMDA increased extracellular choline and activated hydrolysis of phosphatidylcholine and phosphatidylinositol by phospholipase A 2 but did not induce significant degradation of phosphatidylcholine, phosphatidylinositol, phosphatidylEthanolamine, or phosphatidylserine. In contrast, NMDA strongly reduced the incorporation of [ 3 H]choline and [ 3 H]Ethanolamine into their respective phospholipids. Metabolic labeling experiments in whole cells showed that NMDA receptor overactivation does not modify the activity of phosphocholine or phosphoEthanolamine cytidylyltransferases but strongly inhibits choline–Ethanolamine Phosphotransferase activity. This effect was observed well before any significant membrane damage and cell death. Moreover, cholinePhosphotransferase activity was lower in microsomes from NMDA-treated cells. These results show that membrane damage by NMDA is preceded by inhibition of phospholipid synthesis and not by phospholipid degradation in the early stages of the excitotoxic process, and that NMDA receptor overactivation decreases phosphatidylcholine and phosphatidylEthanolamine synthesis by inhibiting choline–ethanolaminoPhosphotransferase activity.
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NMDA Receptor Overactivation Inhibits Phospholipid Synthesis by Decreasing Choline–Ethanolamine Phosphotransferase Activity
The Journal of Neuroscience, 2003Co-Authors: Teresa Gasull, Elisabet Sarri, Nuria Degregorio-rocasolano, Ramon TrullasAbstract:Overactivation of NMDA receptors is believed to induce neuronal death by increasing phospholipid hydrolysis and subsequent degradation. We showed previously that NMDA releases choline and inhibits incorporation of [ 3 H]choline into phosphatidylcholine before excitotoxic neuronal death. On the basis of these results, we hypothesized that excitotoxicity results from inhibition of synthesis rather than from increased degradation of phospholipids. We now investigated the effect of NMDA receptor overactivation on synthesis and degradation of major membrane phospholipids in the early stages of the excitotoxic process. Exposure of cortical neurons to neurotoxic concentrations of NMDA increased extracellular choline and activated hydrolysis of phosphatidylcholine and phosphatidylinositol by phospholipase A 2 but did not induce significant degradation of phosphatidylcholine, phosphatidylinositol, phosphatidylEthanolamine, or phosphatidylserine. In contrast, NMDA strongly reduced the incorporation of [ 3 H]choline and [ 3 H]Ethanolamine into their respective phospholipids. Metabolic labeling experiments in whole cells showed that NMDA receptor overactivation does not modify the activity of phosphocholine or phosphoEthanolamine cytidylyltransferases but strongly inhibits choline–Ethanolamine Phosphotransferase activity. This effect was observed well before any significant membrane damage and cell death. Moreover, cholinePhosphotransferase activity was lower in microsomes from NMDA-treated cells. These results show that membrane damage by NMDA is preceded by inhibition of phospholipid synthesis and not by phospholipid degradation in the early stages of the excitotoxic process, and that NMDA receptor overactivation decreases phosphatidylcholine and phosphatidylEthanolamine synthesis by inhibiting choline–ethanolaminoPhosphotransferase activity.