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Dongsoon Im - One of the best experts on this subject based on the ideXlab platform.
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calcium signaling of Lysophosphatidylethanolamine through lpa1 in human sh sy5y neuroblastoma cells
Biomolecules & Therapeutics, 2017Co-Authors: Soojin Park, Dongsoon ImAbstract:: Lysophosphatidylethanolamine (LPE), a lyso-type metabolite of phosphatidylethanolamine, has been reported to be an intercellular signaling molecule. LPE mobilizes intracellular Ca2+ through G-protein-coupled receptor (GPCR) in some cells types. However, GPCRs for lysophosphatidic acid (LPA) were not implicated in the LPE-mediated activities in LPA GPCR overexpression systems or in SK-OV3 ovarian cancer cells. In the present study, in human SH-SY5Y neuroblastoma cells, experiments with LPA1 antagonists showed LPE induced intracellular Ca2+ increases in an LPA1 GPCR-dependent manner. Furthermore, LPE increased intracellular Ca2+ through pertussis-sensitive G proteins, edelfosine-sensitive-phospholipase C, 2-APB-sensitive IP3 receptors, Ca2+ release from intracellular Ca2+ stores, and subsequent Ca2+ influx across plasma membranes, and LPA acted on LPA1 and LPA2 receptors to induce Ca2+ response in a 2-APB-sensitive and insensitive manner. These findings suggest novel involvements for LPE and LPA in calcium signaling in human SH-SY5Y neuroblastoma cells.
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g protein coupled receptors for Lysophosphatidylethanolamine
Receptors and clinical investigation, 2015Co-Authors: Soojin Park, Dongsoon ImAbstract:Lysophospholipids like lysophosphatidic acid (LPA) and sphingosine 1-phosphate have been intensively studied over the last several decades, and these studies have resulted in the identification of their G protein-coupled receptors (GPCR) and in the discoveries of new drugs targeting GPCRs. However, Lysophosphatidylethanolamine (LPE) has not attracted much research attention. Recently, we found several interesting points regarding the action and signaling of LPE, that is, its cell-type dependence, structure specificity, and unique signaling. In particular, LPE signaling through LPA 1 receptor (type 1 lysophosphatidic acid receptor) was found to be cell type dependent, and LPEs with different chain lengths induced different responses in different cells without LPA 1 involvement. Here, we review recent findings and propose possible action modes of LPE GPCRs in different cells.
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Lysophosphatidylethanolamine increases intracellular ca2 through lpa1 in pc 12 neuronal cells
Biochemical and Biophysical Research Communications, 2015Co-Authors: Soojin Park, Dongsoon ImAbstract:G protein-coupled receptors (GPCRs) have been implicated in Lysophosphatidylethanolamine (LPE)-induced increases in intracellular Ca2+ ([Ca2+]i), but in different cell types, this response may be dependent or independent of lysophosphatidic acid (LPA) GPCR. The effects of LPEs from Grifola frondosa on the neuronal differentiation and apoptosis of PC-12 neuronal cells have been previously reported. In the present study, the authors sought to identify the mechanism responsible for the effects of LPEs in PC-12 neuronal cells. LPE increase [Ca2+]i concentration-dependently in PC-12 neuronal cells, but this LPE-induced [Ca2+]i increase was less than that elicited by LPA. Studies using specific inhibitors showed that LPE-induced Ca2+ response was mediated via pertussis toxin-sensitive Gi/o proteins, edelfosine-sensitive phospholipase C, and 2-APB-sensitive IP3 receptor and by Ca2+ influx across the cell membrane, and that this did not involve the conversion of LPE to LPA. Furthermore, LPE- and LPA-induced responses were found to show homologous and heterologous desensitization in PC-12 cells. VPC32183 and Ki16425 (antagonists of LPA1 and LPA3) inhibited LPE-induced [Ca2+]i increases. Furthermore, AM-095 (a specific inhibitor of LPA1) inhibited LPE-induced Ca2+ response completely in PC-12 cells. These findings indicate LPE increases [Ca2+]i via a LPA1/Gi/o proteins/phospholipase C/IP3/Ca2+ rise/Ca2+ influx pathway in PC-12 neuronal cells.
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action and signaling of Lysophosphatidylethanolamine in mda mb 231 breast cancer cells
Biomolecules & Therapeutics, 2014Co-Authors: Soojin Park, Dongsoon ImAbstract:Previously, we reported that Lysophosphatidylethanolamine (LPE), a lyso-type metabolite of phosphatidylethanolamine, can increase intracellular Ca2+ ([Ca2+]i) via type 1 lysophosphatidic acid (LPA) receptor (LPA1) and CD97, an adhesion G-protein-coupled receptor (GPCR), in MDA-MB-231 breast cancer cells. Furthermore, LPE signaling was suggested as like LPA1/CD97-Gi/o proteins-phospholipase C-IP3-Ca2+ increase in these cells. In the present study, we further investigated actions of LPE not only in the [Ca2+]i increasing effect but also in cell proliferation and migration in MDA-MB-231 breast cancer cells. We utilized chemically different LPEs and a specific inhibitor of LPA1, AM-095 in comparison with responses in SK-OV3 ovarian cancer cells. It was found that LPE-induced Ca2+ response in MDA-MB-231 cells was evoked in a different manner to that in SK-OV3 cells in terms of structural requirements. AM-095 inhibited LPE-induced Ca2+ response and cell proliferation in MDA-MB-231 cells, but not in SK-OV3 cells, supporting LPA1 involvement only in MDA-MB-231 cells. LPA had significant effects on cell proliferation and migration in MDA-MB-231 cells, whereas LPE had less or no significant effect. However, LPE modulations of MAPKs (ERK1/2, JNK and p38 MAPK) was not different to those by LPA in the cells. These data support the involvement of LPA1 in LPE-induced Ca2+ response and cell proliferation in breast MDA-MB-231 cells but unknown GPCRs (not LPA1) in LPE-induced responses in SK-OV3 cells. Furthermore, although LPE and LPA utilized LPA1, LPA utilized more signaling cascades than LPE, resulting in stronger responses by LPA in proliferation and migration than LPE in MDA-MB-231 cells.
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Lysophosphatidylethanolamine utilizes lpa1 and cd97 in mda mb 231 breast cancer cells
Cellular Signalling, 2013Co-Authors: Soojin Park, Saeromi Kang, Hae Young Chung, Fumikazu Okajima, Dongsoon ImAbstract:Abstract Lysophosphatidylethanolamine (LPE) is a lyso-type metabolite of phosphatidylethanolamine (a plasma membrane component), and its intracellular Ca 2 + ([Ca 2 + ] i ) increasing actions may be mediated through G-protein-coupled receptor (GPCR). However, GPCRs for lysophosphatidic acid (LPA), a structurally similar representative lipid mediator, have not been implicated in LPE-mediated activities in SK-OV3 or OVCAR-3 ovarian cancer cells or in receptor over-expression systems. In the present study, LPE-induced [Ca 2 + ] i increase was observed in MDA-MB-231 cells but not in other breast cancer cell lines. In addition, LPE- and LPA-induced responses showed homologous and heterologous desensitization. Furthermore, VPC32183 and Ki16425 (antagonists of LPA 1 and LPA 3 ) inhibited LPE-induced [Ca 2 + ] i increases, and knockdown of LPA 1 by transfection with LPA 1 siRNA completely inhibited LPE-induced [Ca 2 + ] i increases. Furthermore, the involvement of CD97 (an adhesion GPCR) in the action of LPA 1 in MDA-MB-231 cells was demonstrated by siRNA transfection. Pertussis toxin (a specific inhibitor of G i/o proteins), edelfosine (an inhibitor of phospholipase C), or 2-APB (an inhibitor of IP 3 receptor) completely inhibited LPE-induced [Ca 2 + ] i increases, whereas HA130, an inhibitor of autotaxin/lysophospholipase D, did not. Therefore, LPE is supposed to act on LPA 1 -CD97/G i/o proteins/phospholipase C/IP 3 /Ca 2 + rise in MDA-MB-231 breast cancer cells.
Jiwan P Palta - One of the best experts on this subject based on the ideXlab platform.
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mitigation of ethylene promoted leaf senescence by a natural lipid Lysophosphatidylethanolamine
Hortscience, 2005Co-Authors: Mustafa Ozgen, Sookhee Park, Jiwan P PaltaAbstract:Mitigation of ethylene promoted leaf senescence by Lysophosphatidylethanolamine (LPE) was studied. Micropropagated 'Russet Burbank' potato (Solanum tuberosum L.,) plantlets were grown on MS media in sterile culture tubes. After 2 weeks of growth, tubes were sealed and ethylene gas was applied to obtain 5 nL·L -1 fi nal concentration in the culture tubes. Observations and measurements were taken two weeks after ethylene injection. Potato plantlets treated with ethylene showed severe leaf senescence symptoms such as epinasty, lack of growth, yellowing and axillary shoot formation. These observations indicate that apical dominance has been lost with ethylene treatment. The same experiment was repeated with different concentrations of LPE in the MS medium. Inclusion of 50 or 100 mg·L -1 of LPE in the medium mitigated the damage normally caused by applied ethylene. Leaves of plantlets exposed simultaneously to LPE and ethylene had signifi cantly higher chlorophyll content and more healthy leaves compared to plantlets grown on medium lacking LPE. Results of this study suggest that LPE may have the potential to retard ethylene-promoted leaf senescence and may mitigate ethylene induced loss in apical dominance of micropropa- gated potato plantlets. Lipids are known to be important in mem- brane structure and energy balance. It is now evident that lipids and lipid-derived metabolites also play a role in critical cellular processes. Studies have shown that membrane lipid-based signaling mediated by phospholipases, such as phospholipase A 2 (PLA 2 ), phospholipase C
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Lysophosphatidylethanolamine accelerates color development and promotes shelf life of cranberries
Hortscience, 2005Co-Authors: Mustafa Ozgen, Karim M Farag, Senay Ozgen, Jiwan P PaltaAbstract:Highly colored cranberries are desired for both fresh and juice markets. Berries accumulate more color when allowed to stay on the vines longer. However, early fall frosts often force growers to harvest before the fruit has reached its optimal color. This is especially true for the berries under the canopy. No product is currently available for grower to accelerate the color development in cranberries. Result from recent studies suggests that a natural lipid, Lysophosphatidylethanolamine (LPE), can accelerate color production in fruit and, at the same time, promote shelf life. LPE is a natural lipid and is commercially derived from egg and soy lecithin. The influence of LPE on anthocyanin accumulation and storage quality of cranberry fruit (Vaccinium macrocarpon Ait. 'Stevens') was studied. Cranberry plants were sprayed with LPE at about 4 weeks before commercial harvest at multiple locations. Experiments were con- ducted in 1997, 1998 and 1999. Fruit samples were taken at 2 and 4 weeks after spray application to determine the changes in the fruit color. Plots were wet harvested using a standard commercial method and stored in a commercial cold storage facility. Mar- ketable fruit were evaluated at 1 and 2 months after cold storage to determine effect of LPE on shelf life of cranberries. In general, a preharvest application of LPE resulted in a 9% to 27% increase in fruit anthocyanin concentration compared to the control. LPE treatments also resulted in 8% to 12% increase in marketable fruit compared to the control following cold storage. Influence of LPE on fruit quality was more appar- ent after 1 month of storage. These results are consistent with the observed effects of LPE on tomatoes. Interestingly ethanol application also enhanced storage quality. Our results suggest that a preharvest application of LPE may have the potential to enhance color and prolong shelf life of cranberry fruit.
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utilisation de Lysophosphatidylethanolamine 18 1 et de lysophosphatidylinositol pour retarder la senescence et accroitre le murissement des fruits
1998Co-Authors: Jiwan P PaltaAbstract:La presente invention porte sur un procede visant a accroitre le murissement et la conservation des fruits et a retarder la senescence des tissus des fruits et d'autres vegetaux. Ce procede consiste a appliquer sur les tissus des fruits et autres vegetaux une quantite efficace d'un lysophospholipide tel que Lysophosphatidylethanolamine (18:1) (appele ici 'LPE' (18:1)) ou lysophosphatidylinositol (appele ici 'LPI'). Les lysophospholipides tels que LPE (18:1) et LPI s'averent etre superieurs a d'autres lysophospholipides pour retarder la senescence et inhiber la phospholipase D, une enzyme cle de la deterioration de la membrane mediatrice dans la senescence des vegetaux. LPE (18:1) et LPI sont d'origine naturelle et sans danger pour l'environnement. Leur utilisation pourrait remplacer de nombreux composes toxiques pour l'environnement qui sont actuellement utilises pour retarder la senescence des fleurs, des fruits et des feuilles et accroitre le murissement.
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inhibition of phospholipase d by Lysophosphatidylethanolamine a lipid derived senescence retardant
Proceedings of the National Academy of Sciences of the United States of America, 1997Co-Authors: Bjorn H Karlsson, Mustafa Ozgen, Jiwan P PaltaAbstract:Phospholipid signaling mediated by lipid-derived second messengers or biologically active lipids is still new and is not well established in plants. We recently have found that Lysophosphatidylethanolamine (LPE), a naturally occurring lipid, retards senescence of leaves, flowers, and postharvest fruits. Phospholipase D (PLD) has been suggested as a key enzyme in mediating the degradation of membrane phospholipids during the early stages of plant senescence. Here we report that LPE inhibited the activity of partially purified cabbage PLD in a cell-free system in a highly specific manner. Inhibition of PLD by LPE was dose-dependent and increased with the length and unsaturation of the LPE acyl chain whereas individual molecular components of LPE such as ethanolamine and free fatty acid had no effect on PLD activity. Enzyme-kinetic analysis suggested noncompetitive inhibition of PLD by LPE. In comparison, the related lysophospholipids such as lysophosphatidylcholine, lysophosphatidylglycerol, and lysophosphotidylserine had no significant effect on PLD activity whereas PLD was stimulated by lysophosphatidic acid and inhibited by lysophosphatidylinositol. Membrane-associated and soluble PLD, extracted from cabbage and castor bean leaf tissues, also was inhibited by LPE. Consistent with acyl-specific inhibition of PLD by LPE, senescence of cranberry fruits as measured by ethylene production was more effectively inhibited according to the increasing acyl chain length and unsaturation of LPE. There are no known specific inhibitors of PLD in plants and animals. We demonstrate specific inhibitory regulation of PLD by a lysophospholipid.
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postharvest dip in a natural lipid Lysophosphatidylethanolamine may prolong vase life of snapdragon flowers
Hortscience, 1997Co-Authors: Navjot Kaur, Jiwan P PaltaAbstract:We investigated the use of Lysophosphatidylethanolamine (LPE) for prolonging vase life of snapdragon (Antirrhinum majus L.). Freshly cut snapdragon spikes were set into a LPE solution at 25 mg.L -1 for 24 h and then transferred to deionized water. The vase life was enhanced by LPE. The flowers on spikes treated with LPE showed symptoms of wilting or browning 4 or 6 days later than those on the spikes given deionized water in inbred or 'Potomac White', respectively. All the spikes were of marketable quality for 5 to 7 days after harvest when treated with LPE, whereas in the control only about half of the flowers were of marketable quality at 2 days after harvest. LPE treatment also delayed fresh mass loss, lowered endogenous ethylene production, and reduced ion leakage. These results suggest that LPE has commercial potential in enhancing vase life of snapdragons.
Kyoung Sun Park - One of the best experts on this subject based on the ideXlab platform.
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Lysophosphatidylethanolamine stimulates chemotactic migration and cellular invasion in sk ov3 human ovarian cancer cells involvement of pertussis toxin sensitive g protein coupled receptor
FEBS Letters, 2007Co-Authors: Kyoung Sun Park, Dongsoon ImAbstract:We investigated whether Lysophosphatidylethanolamine (LPE) modulates cellular signaling in different cell types. SK-OV3 ovarian cancer cells and OVCAR-3 ovarian cancer cells were responsive to LPE. LPE-stimulated intracellular calcium concentration ([Ca2+]i) increase was inhibited by U-73122, suggesting that LPE stimulates calcium signaling via phospholipase C activation. Moreover, pertussis toxin (PTX) almost completely inhibited [Ca2+]i increase by LPE, indicating the involvement of PTX-sensitive G-proteins. Furthermore, we found that LPE stimulated chemotactic migration and cellular invasion in SK-OV3 ovarian cancer cells. We examined the role of lysophosphatidic acid receptors on LPE-stimulated cellular responses using HepG2 cells transfected with different LPA receptors, and found that LPE failed to stimulate nuclear factor kappa B-driven luciferase. We suggest that LPE stimulates a membrane bound receptor, different from well known LPA receptors, resulting in chemotactic migration and cellular invasion in SK-OV3 ovarian cancer cells.
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Lysophosphatidylethanolamine stimulates chemotactic migration and cellular invasion in SK‐OV3 human ovarian cancer cells: Involvement of pertussis toxin‐sensitive G‐protein coupled receptor
FEBS Letters, 2007Co-Authors: Kyoung Sun Park, Dongsoon ImAbstract:We investigated whether Lysophosphatidylethanolamine (LPE) modulates cellular signaling in different cell types. SK-OV3 ovarian cancer cells and OVCAR-3 ovarian cancer cells were responsive to LPE. LPE-stimulated intracellular calcium concentration ([Ca2+]i) increase was inhibited by U-73122, suggesting that LPE stimulates calcium signaling via phospholipase C activation. Moreover, pertussis toxin (PTX) almost completely inhibited [Ca2+]i increase by LPE, indicating the involvement of PTX-sensitive G-proteins. Furthermore, we found that LPE stimulated chemotactic migration and cellular invasion in SK-OV3 ovarian cancer cells. We examined the role of lysophosphatidic acid receptors on LPE-stimulated cellular responses using HepG2 cells transfected with different LPA receptors, and found that LPE failed to stimulate nuclear factor kappa B-driven luciferase. We suggest that LPE stimulates a membrane bound receptor, different from well known LPA receptors, resulting in chemotactic migration and cellular invasion in SK-OV3 ovarian cancer cells.
Domingos P. F. Almeida - One of the best experts on this subject based on the ideXlab platform.
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Lysophosphatidylethanolamine effects on horticultural commodities a review
Postharvest Biology and Technology, 2013Co-Authors: A. L. Amaro, Domingos P. F. AlmeidaAbstract:Abstract Lysophosphatidylethanolamine (LPE) is a naturally occurring lipid with regulatory effects in senescence and ripening. When applied exogenously to horticultural crops, LPE affects growth, development, and postharvest longevity. The effects of exogenously applied LPE have been studied in a range of plant organs in more than a dozen horticultural species. The claimed horticultural benefits include delayed leaf senescence, stimulation of ripening in table grape, acceleration of color development and extension of shelf-life in cranberry and tomato, and increased vase life of cut flowers. Responses to LPE application are found to vary dramatically within horticultural commodity, developmental stage, and organ type. Effects on ethylene responses are contradictory. LPE inhibits phospholipase D and is reported to affect the activity of enzymes relevant for produce quality, such as phenylalanine ammonia lyase and acid invertase. The biochemical mode of action of LPE is poorly understood. In particular, a mechanism by which a plant growth regulator might delay senescence of plant organs and accelerate ripening-related changes is not obvious. The horticultural, physiological and biochemical effects of LPE are reviewed in an attempt to highlight the knowledge gaps regarding the putative regulatory role of exogenously applied LPE.
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Lysophosphatidylethanolamine effects on horticultural commodities: A review
Postharvest Biology and Technology, 2013Co-Authors: A. L. Amaro, Domingos P. F. AlmeidaAbstract:Lysophosphatidylethanolamine (LPE) is a naturally occurring lipid with regulatory effects in senescence and ripening. When applied exogenously to horticultural crops, LPE affects growth, development, and postharvest longevity. The effects of exogenously applied LPE have been studied in a range of plant organs in more than a dozen horticultural species. The claimed horticultural benefits include delayed leaf senescence, stimulation of ripening in table grape, acceleration of color development and extension of shelf-life in cranberry and tomato, and increased vase life of cut flowers. Responses to LPE application are found to vary dramatically within horticultural commodity, developmental stage, and organ type. Effects on ethylene responses are contradictory. LPE inhibits phospholipase D and is reported to affect the activity of enzymes relevant for produce quality, such as phenylalanine ammonia lyase and acid invertase. The biochemical mode of action of LPE is poorly understood. In particular, a mechanism by which a plant growth regulator might delay senescence of plant organs and accelerate ripening-related changes is not obvious. The horticultural, physiological and biochemical effects of LPE are reviewed in an attempt to highlight the knowledge gaps regarding the putative regulatory role of exogenously applied LPE. © 2012 Elsevier B.V.
Soojin Park - One of the best experts on this subject based on the ideXlab platform.
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calcium signaling of Lysophosphatidylethanolamine through lpa1 in human sh sy5y neuroblastoma cells
Biomolecules & Therapeutics, 2017Co-Authors: Soojin Park, Dongsoon ImAbstract:: Lysophosphatidylethanolamine (LPE), a lyso-type metabolite of phosphatidylethanolamine, has been reported to be an intercellular signaling molecule. LPE mobilizes intracellular Ca2+ through G-protein-coupled receptor (GPCR) in some cells types. However, GPCRs for lysophosphatidic acid (LPA) were not implicated in the LPE-mediated activities in LPA GPCR overexpression systems or in SK-OV3 ovarian cancer cells. In the present study, in human SH-SY5Y neuroblastoma cells, experiments with LPA1 antagonists showed LPE induced intracellular Ca2+ increases in an LPA1 GPCR-dependent manner. Furthermore, LPE increased intracellular Ca2+ through pertussis-sensitive G proteins, edelfosine-sensitive-phospholipase C, 2-APB-sensitive IP3 receptors, Ca2+ release from intracellular Ca2+ stores, and subsequent Ca2+ influx across plasma membranes, and LPA acted on LPA1 and LPA2 receptors to induce Ca2+ response in a 2-APB-sensitive and insensitive manner. These findings suggest novel involvements for LPE and LPA in calcium signaling in human SH-SY5Y neuroblastoma cells.
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g protein coupled receptors for Lysophosphatidylethanolamine
Receptors and clinical investigation, 2015Co-Authors: Soojin Park, Dongsoon ImAbstract:Lysophospholipids like lysophosphatidic acid (LPA) and sphingosine 1-phosphate have been intensively studied over the last several decades, and these studies have resulted in the identification of their G protein-coupled receptors (GPCR) and in the discoveries of new drugs targeting GPCRs. However, Lysophosphatidylethanolamine (LPE) has not attracted much research attention. Recently, we found several interesting points regarding the action and signaling of LPE, that is, its cell-type dependence, structure specificity, and unique signaling. In particular, LPE signaling through LPA 1 receptor (type 1 lysophosphatidic acid receptor) was found to be cell type dependent, and LPEs with different chain lengths induced different responses in different cells without LPA 1 involvement. Here, we review recent findings and propose possible action modes of LPE GPCRs in different cells.
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Lysophosphatidylethanolamine increases intracellular ca2 through lpa1 in pc 12 neuronal cells
Biochemical and Biophysical Research Communications, 2015Co-Authors: Soojin Park, Dongsoon ImAbstract:G protein-coupled receptors (GPCRs) have been implicated in Lysophosphatidylethanolamine (LPE)-induced increases in intracellular Ca2+ ([Ca2+]i), but in different cell types, this response may be dependent or independent of lysophosphatidic acid (LPA) GPCR. The effects of LPEs from Grifola frondosa on the neuronal differentiation and apoptosis of PC-12 neuronal cells have been previously reported. In the present study, the authors sought to identify the mechanism responsible for the effects of LPEs in PC-12 neuronal cells. LPE increase [Ca2+]i concentration-dependently in PC-12 neuronal cells, but this LPE-induced [Ca2+]i increase was less than that elicited by LPA. Studies using specific inhibitors showed that LPE-induced Ca2+ response was mediated via pertussis toxin-sensitive Gi/o proteins, edelfosine-sensitive phospholipase C, and 2-APB-sensitive IP3 receptor and by Ca2+ influx across the cell membrane, and that this did not involve the conversion of LPE to LPA. Furthermore, LPE- and LPA-induced responses were found to show homologous and heterologous desensitization in PC-12 cells. VPC32183 and Ki16425 (antagonists of LPA1 and LPA3) inhibited LPE-induced [Ca2+]i increases. Furthermore, AM-095 (a specific inhibitor of LPA1) inhibited LPE-induced Ca2+ response completely in PC-12 cells. These findings indicate LPE increases [Ca2+]i via a LPA1/Gi/o proteins/phospholipase C/IP3/Ca2+ rise/Ca2+ influx pathway in PC-12 neuronal cells.
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action and signaling of Lysophosphatidylethanolamine in mda mb 231 breast cancer cells
Biomolecules & Therapeutics, 2014Co-Authors: Soojin Park, Dongsoon ImAbstract:Previously, we reported that Lysophosphatidylethanolamine (LPE), a lyso-type metabolite of phosphatidylethanolamine, can increase intracellular Ca2+ ([Ca2+]i) via type 1 lysophosphatidic acid (LPA) receptor (LPA1) and CD97, an adhesion G-protein-coupled receptor (GPCR), in MDA-MB-231 breast cancer cells. Furthermore, LPE signaling was suggested as like LPA1/CD97-Gi/o proteins-phospholipase C-IP3-Ca2+ increase in these cells. In the present study, we further investigated actions of LPE not only in the [Ca2+]i increasing effect but also in cell proliferation and migration in MDA-MB-231 breast cancer cells. We utilized chemically different LPEs and a specific inhibitor of LPA1, AM-095 in comparison with responses in SK-OV3 ovarian cancer cells. It was found that LPE-induced Ca2+ response in MDA-MB-231 cells was evoked in a different manner to that in SK-OV3 cells in terms of structural requirements. AM-095 inhibited LPE-induced Ca2+ response and cell proliferation in MDA-MB-231 cells, but not in SK-OV3 cells, supporting LPA1 involvement only in MDA-MB-231 cells. LPA had significant effects on cell proliferation and migration in MDA-MB-231 cells, whereas LPE had less or no significant effect. However, LPE modulations of MAPKs (ERK1/2, JNK and p38 MAPK) was not different to those by LPA in the cells. These data support the involvement of LPA1 in LPE-induced Ca2+ response and cell proliferation in breast MDA-MB-231 cells but unknown GPCRs (not LPA1) in LPE-induced responses in SK-OV3 cells. Furthermore, although LPE and LPA utilized LPA1, LPA utilized more signaling cascades than LPE, resulting in stronger responses by LPA in proliferation and migration than LPE in MDA-MB-231 cells.
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Lysophosphatidylethanolamine utilizes lpa1 and cd97 in mda mb 231 breast cancer cells
Cellular Signalling, 2013Co-Authors: Soojin Park, Saeromi Kang, Hae Young Chung, Fumikazu Okajima, Dongsoon ImAbstract:Abstract Lysophosphatidylethanolamine (LPE) is a lyso-type metabolite of phosphatidylethanolamine (a plasma membrane component), and its intracellular Ca 2 + ([Ca 2 + ] i ) increasing actions may be mediated through G-protein-coupled receptor (GPCR). However, GPCRs for lysophosphatidic acid (LPA), a structurally similar representative lipid mediator, have not been implicated in LPE-mediated activities in SK-OV3 or OVCAR-3 ovarian cancer cells or in receptor over-expression systems. In the present study, LPE-induced [Ca 2 + ] i increase was observed in MDA-MB-231 cells but not in other breast cancer cell lines. In addition, LPE- and LPA-induced responses showed homologous and heterologous desensitization. Furthermore, VPC32183 and Ki16425 (antagonists of LPA 1 and LPA 3 ) inhibited LPE-induced [Ca 2 + ] i increases, and knockdown of LPA 1 by transfection with LPA 1 siRNA completely inhibited LPE-induced [Ca 2 + ] i increases. Furthermore, the involvement of CD97 (an adhesion GPCR) in the action of LPA 1 in MDA-MB-231 cells was demonstrated by siRNA transfection. Pertussis toxin (a specific inhibitor of G i/o proteins), edelfosine (an inhibitor of phospholipase C), or 2-APB (an inhibitor of IP 3 receptor) completely inhibited LPE-induced [Ca 2 + ] i increases, whereas HA130, an inhibitor of autotaxin/lysophospholipase D, did not. Therefore, LPE is supposed to act on LPA 1 -CD97/G i/o proteins/phospholipase C/IP 3 /Ca 2 + rise in MDA-MB-231 breast cancer cells.