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Lena Gustavsson - One of the best experts on this subject based on the ideXlab platform.
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Effect of calmodulin antagonists on phospholipase D activity in SH-SY5Y cells
Neurochemistry International, 2002Co-Authors: María Del Carmen Boyano-adánez, Lena GustavssonAbstract:The aim of this study was to investigate the involvement of calmodulin in phospholipase D activation in SH-SY5Y cells. Cells prelabelled with [3H]-palmitic acid were incubated with calmodulin antagonists and/or other compounds. Phosphatidylethanol, a specific marker for phospholipase D activity, and phosphatidic acid were analysed. The calmodulin antagonists, calmidazolium and trifluoperazine, induced an extensive increase in Phosphatidylethanol formation, and thus increased basal phospholipase D activity, in a dose- and time-dependent manner. The effect of calmidazolium on carbachol-induced activation of muscarinic receptors was also studied. Calmidazolium did not significantly affect the amount of Phosphatidylethanol formed following carbachol addition. However, taking into account the increase in basal activity observed after calmidazolium addition, calmidazolium probably inhibits the muscarinic receptor-induced phospholipase D activation. In addition to Phosphatidylethanol, basal phosphatidic acid levels were also increased after calmidazolium and trifluoperazine addition. Incubation with calmidazolium (10 microM) for 10 min induced a two-fold increase in phosphatidic acid. The calmidazolium-induced increase in basal phospholipase D activity was not affected by the protein kinase inhibitors H7 and staurosporine. On the other hand tyrosine kinase inhibitors abolished the calmidazolium-induced activation of phospholipase D. Calmidazolium also induced tyrosine phosphorylation in parallel to the phospholipase D activation. In conclusion, our data indicate that calmodulin antagonists induce phospholipase D activity in SH-SY5Y cells via a tyrosine kinase dependent pathway. This may point to a negative control of phospholipase D by calmodulin although a calmodulin-independent mechanism cannot be excluded. Calmodulin antagonists may be useful tools to further elucidate the mechanisms of phospholipase D regulation. (Less)
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Characterization of Phospholipase D Activation by Muscarinic Receptors in Human Neuroblastoma SH-SY5Y Cells
Neuropharmacology, 1997Co-Authors: María Del Carmen Boyano-adánez, Christer Larsson, Christofer Lundqvist, Lena GustavssonAbstract:The cholinergic regulation of phospholipase D activity was studied in SH-SY5Y human neuroblastoma cells with Phosphatidylethanol formation as a specific marker for the enzyme activity. The muscarinic antagonists, hexahydrosiladifenidol and pirenzepine, inhibited carbachol-induced Phosphatidylethanol formation in a concentration-dependent manner and the inhibitory constants indicated that muscarinic M1 receptors are responsible for the major part of the phospholipase D activation. The mechanism of receptor-mediated phospholipase D activation varies between different cell types and receptors. In SH-SY5Y cells, the carbachol-induced phospholipase D activity was inhibited by protein kinase C inhibitors. Since both phospholipases D and C are activated by muscarinic stimulation in SH-SY5Y cells, most of the phospholipase D activation is probably secondary to the protein kinase C activation that follows phospholipase C-mediated increase in diacylglycerols. Other kinases may be involved in the regulation since also a tyrosine kinase inhibitor decreased the Phosphatidylethanol formation. Stimulation of G-protein(s) and increase in the intracellular Ca2+ concentration activated phospholipase D and may be additional mechanisms for the muscarinic regulation of phospholipase D in SH-SY5Y cells. Propranolol, an inhibitor of phosphatidic acid phosphohydrolase, increased the carbachol-induced formation of phosphatidic acid at the expense of 1,2-diacylglycerol. This indicates that phospholipase D contributes to the formation of 1,2-diacylglycerol after carbachol stimulation in SH-SY5Y cells.
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blood Phosphatidylethanol as a marker of alcohol abuse levels in alcoholic males during withdrawal
Alcoholism: Clinical and Experimental Research, 1997Co-Authors: Per Hansson, Lena Gustavsson, Goran Johnson, Murielle Caron, Christer AllingAbstract:: Phosphatidylethanol (PEth) is formed only in the presence of ethanol, via the action of phospholipase D. We studied PEth in blood as a possible marker of alcohol abuse in 15 male alcoholics admitted for detoxification. Blood was drawn on the first day after admission and up to 28 days thereafter. PEth in whole blood was 13.2 +/- 2.2 mumol liter-1 (mean +/- SE) at first sampling and remained detectable up to 14 days after admission. Blood ethanol was 0 on the morning after admission. The time courses of PEth disappearance varied among individuals. No PEth could be found in blood of control persons who had abstained from ethanol for 4 days. Levels of PEth and carbohydrate-deficient transferrin or gamma-glutamyltranspeptidase did not correlate. Its high specificity and prolonged detectability suggest PEth in blood as a marker of recent alcohol abuse.
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Regulation of phospholipase D activity in neuroblastoma cells
Journal of Lipid Mediators and Cell Signalling, 1996Co-Authors: Lena Gustavsson, María Del Carmen Boyano-adánez, Christer Larsson, Steina Aradottir, Christofer LundqvistAbstract:The regulation of phospholipase D was studied in human neuroblastoma cells using Phosphatidylethanol as a marker of the enzyme activity. Carbachol induced phospholipase D activity in SH-SY5Y cells. Muscarinic antagonists inhibited the response with potencies suggesting that muscarinic M1 receptors are responsible for the activation. In permeabilized SH-SY5Y cells, both the carbachol- and GTP gamma S-induced Peth formation was inhibited by GDP beta S, indicating that both responses are mediated via a G-protein. The protein kinase C inhibitors, bisindolylmaleimide and staurosporine significantly inhibited the carbachol-induced Peth formation whereas H7 had no effect. Thus, the cholinergic activation of phospholipase D in SH-SY5Y cells is probably mediated via a direct receptor-G-protein coupling but an involvement of protein kinase C cannot be excluded. Calmidazolium, a calmodulin antagonist, induced an increase in Phosphatidylethanol formation in both SH-SY5Y and IMR-32 cells. This effect was inhibited by genistein and tyrphostin, indicating a tyrosine kinase dependent pathway for phospholipase D activation in neuroblastoma cells. (Less)
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ETHANOL AND Phosphatidylethanol REDUCE THE BINDING OF [3H]INOSITOL 1,4,5-TRISPHOSPHATE TO RAT CEREBELLAR MEMBRANES
Alcohol and Alcoholism, 1996Co-Authors: F D Rodriguez, Christer Alling, Christofer Lundqvist, Lena GustavssonAbstract:In this study, we have analysed the effect of ethanol and Phosphatidylethanol, a unique phospholipid formed only in the presence of ethanol, on the binding of [3H]inositol 1,4,5-trisphosphate to rat cerebellar membranes. Rats were intraperitoneally injected daily with 3 g of ethanol/kg body weight for different periods of time. Repeated administration of ethanol induced a reduction in the binding capacity ( B max) without affecting the affinity constant ( K d). A significant 32% reduction was observed after 21 days of exposure (from control B max values of 25±3 pmol/mg and K d values of 9±2 nM). In an in-vitro assay, Phosphatidylethanol (500 μM) and phosphatidic acid (500 μM), but no other phospholipids tested, induced a reduction in B max (39% and 43%, respectively). The observed effect displayed by Phosphatidylethanol was not due to its degradation to phosphatidic acid or other phospholipids. The results emphasize the importance of examining Phosphatidylethanol (PEth) as a possible mediator of the effects of ethanol on cellular processes. However, the role of PEth in the observed effect of long-term ethanol exposure still needs further consideration.
Christofer Lundqvist - One of the best experts on this subject based on the ideXlab platform.
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Phosphatidylethanol in rat organs after ethanol exposure
Alcoholism: Clinical and Experimental Research, 2002Co-Authors: Steina Aradottir, Christofer Lundqvist, Christer AllingAbstract:BACKGROUND: Phosphatidylethanol (PEth) is an abnormal phospholipid formed in mammalian cells that have been exposed to ethanol. It has been suggested that PEth mediates some of the damaging effects of ethanol on cells. This study was performed to investigate the level of PEth in organs of rats after in vivo alcohol exposure. METHODS: Three exposure models were studied: (1) acute, intraperitoneal injection of ethanol (n = 3 x 3); (2) chronic, forced ethanol drinking (n = 6); and (3) chronic, free choice of ethanol (n = 20). PEth was analyzed by high-performance liquid chromatography after lipid extraction of the organs. RESULTS: One acute injection gave detectable PEth levels in most organs analyzed, with maximal levels reached after 2 hr. The highest levels were reached in intestines, stomach, and lung. No PEth was detected in skeletal muscle, pancreas, or testis. The two exposure models for oral intake of ethanol also gave detectable PEth levels in most organs. The highest levels were reached in stomach, lung, and spleen. PEth was detected in muscle only in animals with heavy total alcohol intake. CONCLUSIONS: PEth is formed in most organs of rats exposed to ethanol acutely or chronically. Variations in PEth level and rates of PEth formation and PEth degradation are organ specific.
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Phosphatidylethanol in blood as a marker of ethanol consumption in healthy volunteers comparison with other markers
Alcoholism: Clinical and Experimental Research, 1998Co-Authors: Arthur Varga, Christofer Lundqvist, Per Hansson, Christer AllingAbstract:: Phosphatidylethanol is a "pathological" phospholipid, formed via the action of phospholipase D only in the presence of ethanol. The present study was made to elucidate how different levels and patterns of alcohol intake affect blood levels of Phosphatidylethanol in comparison with other markers of abuse. We used a new HPLC-evaporative light-scattering detection technique for Phosphatidylethanol quantitation. This method had a total coefficient of variation of <20% at the detection limit of 0.2 nmol, equaling 0.8 micromol/liter of whole blood. Two groups were studied. (a) Five healthy volunteers were given 32 to 47 g of ethanol in a single dose, to give blood ethanol levels of approximately 25 mmol/liter after 30 to 60 min. Phosphatidylethanol, carbohydrate-deficient transferrin (CDT), and blood ethanol were measured before and after the intake. (b) Twelve student volunteers were studied during a 3 week period of prolonged alcohol consumption (total estimated intake: 1334 +/- 488 g, mean +/- SD) and Phosphatidylethanol, serum-CDT, gamma-glutamyltransferase, and blood ethanol were measured at the start of the period (day 1) and twice at the end of the period (days 18 and 21). In group (a), no Phosphatidylethanol was detected at any time after ethanol dosage/intake. In group (b), no blood Phosphatidylethanol or blood ethanol could be demonstrated at the start, and serum-CDT was below the discrimination limit (1.3%) in all persons. No Phosphatidylethanol was detected in those four persons with the lowest intake (742 +/- 150 g). However, the remaining eight persons had detectable levels of Phosphatidylethanol (1.0 to 2.1 micromol/liter), and these had a higher total intake (1630 +/- 389 g). There was a statistically significant (p = 0.02) increase in serum CDT for 3 weeks. However, only 3 of 12 persons increased above the discrimination limit. The present results indicate that a substantial alcohol intake is needed to elevate blood Phosphatidylethanol. In comparison with serum-CDT, blood Phosphatidylethanol appears more sensitive.
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Phosphatidylethanol in blood as a marker of ethanol consumption in healthy volunteers : Comparison with other markers
Alcoholism: Clinical and Experimental Research, 1998Co-Authors: Arthur Varga, Christofer Lundqvist, Per Hansson, Christer AllingAbstract:: Phosphatidylethanol is a "pathological" phospholipid, formed via the action of phospholipase D only in the presence of ethanol. The present study was made to elucidate how different levels and patterns of alcohol intake affect blood levels of Phosphatidylethanol in comparison with other markers of abuse. We used a new HPLC-evaporative light-scattering detection technique for Phosphatidylethanol quantitation. This method had a total coefficient of variation of
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Characterization of Phospholipase D Activation by Muscarinic Receptors in Human Neuroblastoma SH-SY5Y Cells
Neuropharmacology, 1997Co-Authors: María Del Carmen Boyano-adánez, Christer Larsson, Christofer Lundqvist, Lena GustavssonAbstract:The cholinergic regulation of phospholipase D activity was studied in SH-SY5Y human neuroblastoma cells with Phosphatidylethanol formation as a specific marker for the enzyme activity. The muscarinic antagonists, hexahydrosiladifenidol and pirenzepine, inhibited carbachol-induced Phosphatidylethanol formation in a concentration-dependent manner and the inhibitory constants indicated that muscarinic M1 receptors are responsible for the major part of the phospholipase D activation. The mechanism of receptor-mediated phospholipase D activation varies between different cell types and receptors. In SH-SY5Y cells, the carbachol-induced phospholipase D activity was inhibited by protein kinase C inhibitors. Since both phospholipases D and C are activated by muscarinic stimulation in SH-SY5Y cells, most of the phospholipase D activation is probably secondary to the protein kinase C activation that follows phospholipase C-mediated increase in diacylglycerols. Other kinases may be involved in the regulation since also a tyrosine kinase inhibitor decreased the Phosphatidylethanol formation. Stimulation of G-protein(s) and increase in the intracellular Ca2+ concentration activated phospholipase D and may be additional mechanisms for the muscarinic regulation of phospholipase D in SH-SY5Y cells. Propranolol, an inhibitor of phosphatidic acid phosphohydrolase, increased the carbachol-induced formation of phosphatidic acid at the expense of 1,2-diacylglycerol. This indicates that phospholipase D contributes to the formation of 1,2-diacylglycerol after carbachol stimulation in SH-SY5Y cells.
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Regulation of phospholipase D activity in neuroblastoma cells
Journal of Lipid Mediators and Cell Signalling, 1996Co-Authors: Lena Gustavsson, María Del Carmen Boyano-adánez, Christer Larsson, Steina Aradottir, Christofer LundqvistAbstract:The regulation of phospholipase D was studied in human neuroblastoma cells using Phosphatidylethanol as a marker of the enzyme activity. Carbachol induced phospholipase D activity in SH-SY5Y cells. Muscarinic antagonists inhibited the response with potencies suggesting that muscarinic M1 receptors are responsible for the activation. In permeabilized SH-SY5Y cells, both the carbachol- and GTP gamma S-induced Peth formation was inhibited by GDP beta S, indicating that both responses are mediated via a G-protein. The protein kinase C inhibitors, bisindolylmaleimide and staurosporine significantly inhibited the carbachol-induced Peth formation whereas H7 had no effect. Thus, the cholinergic activation of phospholipase D in SH-SY5Y cells is probably mediated via a direct receptor-G-protein coupling but an involvement of protein kinase C cannot be excluded. Calmidazolium, a calmodulin antagonist, induced an increase in Phosphatidylethanol formation in both SH-SY5Y and IMR-32 cells. This effect was inhibited by genistein and tyrphostin, indicating a tyrosine kinase dependent pathway for phospholipase D activation in neuroblastoma cells. (Less)
Christer Alling - One of the best experts on this subject based on the ideXlab platform.
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Phosphatidylethanol formation and degradation in human and rat blood
Alcohol and Alcoholism, 2004Co-Authors: Steina Aradottir, K Moller, Christer AllingAbstract:Aims: To investigate the rate of formation and degradation of Phosphatidylethanol (PEth) in rat blood as compared to human blood, as a model for a biological marker for ethanol exposure. Methods: Rats were given 9% ethanol in liquid diet for 30 days. Control rats were pair fed with a control liquid diet. Blood and organs were analysed considering PEth formed in vivo. Blood from man, rat, pig and ferret as well as human HepG2 cells and rat C6 glioma cells were studied with respect to formation and degradation of PEth in vitro. PEth was analysed by high performance liquid chromatography (HPLC). Results: Most rat organs accumulated considerable amounts of PEth whereas no PEth was found in the blood. After in vitro incubations of blood with ethanol, PEth was only formed by human blood, in contrast to the other species studied. HepG2 cells and C6 cells, like human blood, formed PEth in vitro but only the two cell lines had enzymatic degradation of PEth. Conclusions: The rat is not suitable as a model for assaying PEth in blood as a consequence of ethanol intake. Human blood seems to be particular in its ability to synthesize PEth and to maintain a stable level of PEth due to the lack of degrading activity.
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Phosphatidylethanol in rat organs after ethanol exposure
Alcoholism: Clinical and Experimental Research, 2002Co-Authors: Steina Aradottir, Christofer Lundqvist, Christer AllingAbstract:BACKGROUND: Phosphatidylethanol (PEth) is an abnormal phospholipid formed in mammalian cells that have been exposed to ethanol. It has been suggested that PEth mediates some of the damaging effects of ethanol on cells. This study was performed to investigate the level of PEth in organs of rats after in vivo alcohol exposure. METHODS: Three exposure models were studied: (1) acute, intraperitoneal injection of ethanol (n = 3 x 3); (2) chronic, forced ethanol drinking (n = 6); and (3) chronic, free choice of ethanol (n = 20). PEth was analyzed by high-performance liquid chromatography after lipid extraction of the organs. RESULTS: One acute injection gave detectable PEth levels in most organs analyzed, with maximal levels reached after 2 hr. The highest levels were reached in intestines, stomach, and lung. No PEth was detected in skeletal muscle, pancreas, or testis. The two exposure models for oral intake of ethanol also gave detectable PEth levels in most organs. The highest levels were reached in stomach, lung, and spleen. PEth was detected in muscle only in animals with heavy total alcohol intake. CONCLUSIONS: PEth is formed in most organs of rats exposed to ethanol acutely or chronically. Variations in PEth level and rates of PEth formation and PEth degradation are organ specific.
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Phosphatidylethanol in post mortem blood as a marker of previous heavy drinking
International Journal of Legal Medicine, 2001Co-Authors: Per Hansson, Arthur Varga, Peter Krantz, Christer AllingAbstract:Phosphatidylethanol (PEth) is an ethanol-phospholipid adduct, formed via non-oxidative metabolism of ethanol. PEth was measured in femoral blood from 85 consecutive forensic autopsies and was detected in 35 of the cases at concentrations ranging from 0.8 to 22.0 μmol/l. Of the PEth positive cases, 12 did not have significant levels of ethanol in the blood. Two cases (both suicides involving hanging) had detectable ethanol, but no PEth present in the blood. We conclude that measurements of PEth provide indications of previous alcohol abuse in cases where this may not otherwise be evident.
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Phosphatidylethanol clinical significance and biochemical basis
2001Co-Authors: Arthur Varga, Steina Aradottir, Per Hansson, K Moller, Christer AllingAbstract:As shown in figure 1, ethanol can be metabolized by oxidative and nonoxidative pathways (Lieber, 1995). In the oxidative pathway, ethanol is converted to acetal-dehyde through the action of alcohol dehydrogenases, the microsomal ethanol-oxidizing system, or catalase. Acetaldehyde is then subsequently metabolized to acetate through the action of aldehyde dehydrogenases. In one of the nonoxidative pathways of ethanol metabolism, ethanol undergoes esterification with fatty acids by the action of fatty acid ethyl ester synthase to form fatty acid ethyl esters. The nonoxidative ethanol pathway that is the focus of this review is the pathway leading to the synthesis of Phosphatidylethanol. Figure 1 shows how ethanol can be inserted as the head group of a phospholipid to form Phosphatidylethanol. The transformation occurs through the activation of phospholipase D, mainly on phosphatidylcholine in the presence of ethanol.
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Phosphatidylethanol in blood as a marker of ethanol consumption in healthy volunteers comparison with other markers
Alcoholism: Clinical and Experimental Research, 1998Co-Authors: Arthur Varga, Christofer Lundqvist, Per Hansson, Christer AllingAbstract:: Phosphatidylethanol is a "pathological" phospholipid, formed via the action of phospholipase D only in the presence of ethanol. The present study was made to elucidate how different levels and patterns of alcohol intake affect blood levels of Phosphatidylethanol in comparison with other markers of abuse. We used a new HPLC-evaporative light-scattering detection technique for Phosphatidylethanol quantitation. This method had a total coefficient of variation of <20% at the detection limit of 0.2 nmol, equaling 0.8 micromol/liter of whole blood. Two groups were studied. (a) Five healthy volunteers were given 32 to 47 g of ethanol in a single dose, to give blood ethanol levels of approximately 25 mmol/liter after 30 to 60 min. Phosphatidylethanol, carbohydrate-deficient transferrin (CDT), and blood ethanol were measured before and after the intake. (b) Twelve student volunteers were studied during a 3 week period of prolonged alcohol consumption (total estimated intake: 1334 +/- 488 g, mean +/- SD) and Phosphatidylethanol, serum-CDT, gamma-glutamyltransferase, and blood ethanol were measured at the start of the period (day 1) and twice at the end of the period (days 18 and 21). In group (a), no Phosphatidylethanol was detected at any time after ethanol dosage/intake. In group (b), no blood Phosphatidylethanol or blood ethanol could be demonstrated at the start, and serum-CDT was below the discrimination limit (1.3%) in all persons. No Phosphatidylethanol was detected in those four persons with the lowest intake (742 +/- 150 g). However, the remaining eight persons had detectable levels of Phosphatidylethanol (1.0 to 2.1 micromol/liter), and these had a higher total intake (1630 +/- 389 g). There was a statistically significant (p = 0.02) increase in serum CDT for 3 weeks. However, only 3 of 12 persons increased above the discrimination limit. The present results indicate that a substantial alcohol intake is needed to elevate blood Phosphatidylethanol. In comparison with serum-CDT, blood Phosphatidylethanol appears more sensitive.
Markku J Savolainen - One of the best experts on this subject based on the ideXlab platform.
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Low plasma antibodies specific for Phosphatidylethanol in alcohol abusers and patients with alcoholic pancreatitis.
Addiction Biology, 2011Co-Authors: Antti Nissinen, Markku J Savolainen, Sakari Kakko, L. Maria Laitinen, Anders Helander, Sohvi HörkköAbstract:Phosphatidylethanol (PEth) is a group of alcohol-modified phospholipids present in cell membranes after heavy drinking. Our aim was to demonstrate the presence of human plasma antibodies binding to PEth and to address their specificity and value in detecting subjects engaged in heavy alcohol consumption. Antibodies to PEth were analyzed in plasma from heavy drinkers (n = 20), patients with alcoholic pancreatitis (n = 58) and control subjects (n = 24), using chemiluminescent immunoassay. Heavy drinkers and patients with alcoholic pancreatitis demonstrated significantly lower levels of plasma IgG, IgA and IgM titers to PEth compared with controls (P
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Phosphatidylethanol mediates its effects on the vascular endothelial growth factor via hdl receptor in endothelial cells
Alcoholism: Clinical and Experimental Research, 2009Co-Authors: Marja K Liisanantti, Markku J SavolainenAbstract:Background: Previous epidemiological studies have shown that light to moderate alcohol consumption has protective effects against coronary heart disease but the mechanisms of the beneficial effect of alcohol are not known. Ethanol may increase high density lipoprotein (HDL) cholesterol concentration, augment the reverse cholesterol transport, or regulate growth factors or adhesion molecules. To study whether qualitative changes in HDL phospholipids mediate part of the beneficial effects of alcohol on atherosclerosis by HDL receptor, we investigated whether Phosphatidylethanol (PEth) in HDL particles affects the secretion of vascular endothelial growth factor (VEGF) by a human scavenger receptor CD36 and LIMPII analog-I (CLA-1)-mediated pathway. Methods: Human EA.hy 926 endothelial cells were incubated in the presence of native HDL or PEth-HDL. VEGF concentration and CLA-1 protein expression were measured. Human CLA-1 receptor-mediated mechanisms in endothelial cells were studied using CLA-1 blocking antibody and protein kinase inhibitors. Results: Phosphatidylethanol-containing HDL particles caused a 6-fold increase in the expression of CLA-1 in endothelial cells compared with the effect of native HDL. That emergent effect was mediated mainly through protein kinase C and p44/42 mitogen-activated protein kinase pathways. PEth increased the secretion of VEGF and that increase could be abolished by a CLA-1 blocking antibody. Conclusions: High density lipoprotein particles containing PEth bind to CLA-1 receptor and thereby increase the secretion of VEGF from endothelial cells. Ethanol-induced protective effects against coronary heart disease may be explained, at least partly, by the effects of PEth-modified HDL particles on VEGF via CLA-1-mediated mechanisms in endothelial cells.
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effects of Phosphatidylethanol on mouse adipocyte differentiation and expression of stearoyl coa desaturase 1
Alcoholism: Clinical and Experimental Research, 2007Co-Authors: Tuija Huusko, Antti Nissinen, Marja K Liisanantti, Sakari Kakko, Eevariitta Savolainen, Jussi Vuoristo, Markku J SavolainenAbstract:BACKGROUND: Phosphatidylethanol (PEth) is an aberrant phospholipid formed in vivo only in the presence of ethanol. In circulation PEth is associated with lipoproteins and is transferred from one lipoprotein to another. Lipoprotein-associated PEth affects endothelial and smooth muscle cells of blood vessels, but its effects on other cell types have not been explored. Adipocytes have a central role in metabolic syndrome and obesity. In this study we tested whether lipoprotein-associated PEth affects stearoyl-CoA desaturase 1 (SCD1) which plays a major role in lipid-mediated signaling in the differentiation of adipocytes. METHODS: Mouse 3T3-L1 preadipocytes were differentiated to adipocytes in the presence of high-density lipoproteins (HDL) isolated from the plasma of healthy volunteers or PEth-containing HDL modified in vitro. After incubation, fat accumulation, SCD1 mRNA expression, SCD1 protein content, and fatty acid composition of adipocytes were determined. RESULTS: Phosphatidylethanol-containing HDL particles inhibited adipocyte differentiation and decreased the 18:1/18:0 ratio of cellular fatty acids by 28% compared with native HDL particles. Moreover, PEth-containing HDL reduced the SCD1 protein content by 39%. CONCLUSIONS: Lipoprotein-associated PEth may mediate the effects of ethanol on SCD1 and differentiation of preadipocytes to adipocytes.
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transfer of Phosphatidylethanol between lipoproteins
Alcoholism: Clinical and Experimental Research, 2004Co-Authors: Marja K Liisanantti, Kimmo Huhta, Markku J SavolainenAbstract:BACKGROUND: Phosphatidylethanol (PEth) is an abnormal phospholipid formed only in the presence of ethanol. It has been recently shown that lipoprotein-associated PEth may mediate the effects of ethanol on endothelial cells, and this may explain, at least in part, the beneficial effect of ethanol on atherosclerosis. This study was performed to investigate the transfer of PEth between lipoproteins and the effects of PEth on cholesteryl ester transfer protein (CETP) activity in plasma. METHODS: Lipoproteins were isolated from the plasma of healthy male volunteers (n = 16) and male alcoholics (n = 13). The transfer of cholesteryl esters and PEth was determined between labeled low-density lipoprotein (LDL) and unlabeled high-density lipoprotein particles in vitro. The electrophoretic mobility of PEth-modified LDL particles was determined by agarose gel electrophoresis. RESULTS: PEth was transferred from PEth-modified LDL to high-density lipoprotein at an initial rate of 25.9 nmol/ml/hr. Monoclonal antibody (TP2) against the putative lipid-binding domain of CETP inhibited the transfer rate of PEth by approximately 64%, whereas the cholesteryl ester transfer was inhibited by 86%. This indicates that most of PEth was transferred by transfer proteins other than CETP. CONCLUSIONS: The transfer of PEth between lipoproteins enables the redistribution of PEth from lipoprotein fractions with a slow turnover to those with a rapid clearance. Moreover, the PEth-induced change in the electrical charge of lipoproteins may affect the binding of lipoproteins to their receptors and binding proteins. This in turn may alter the metabolism of lipoproteins and lipid-mediated signaling pathways in the cells delineating the vascular wall.
Marja K Liisanantti - One of the best experts on this subject based on the ideXlab platform.
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Phosphatidylethanol in lipoproteins as a regulator of vascular endothelial growth factor in vascular wall cells
2020Co-Authors: Marja K LiisananttiAbstract:Phosphatidylethanol (PEth) is an abnormal phospholipid formed only in the presence of ethanol. Ethanol causes changes in the concentration and composition of plasma lipoproteins and it also influences the enzymes and transfer proteins that modify lipoproteins in plasma. PEth might be one of these changes brought on by ethanol in the circulation. The present study was designed to investigate whether qualitative changes in high density lipoprotein (HDL) phospholipids caused by ethanol can mediate the beneficial effects of alcohol on atherosclerosis, and to investigate the transfer of PEth between lipoproteins and the effects of PEth on the charge of lipoprotein particles. PEth was shown to be transferred from low density lipoproteins (LDL) to HDL particles mainly by transfer proteins other than cholesteryl ester transfer protein (CETP). The transfer of PEth between lipoproteins enables the redistribution of PEth between lipoproteins in plasma. The results of this study provide evidence that PEth in HDL particles stimulates the vascular endothelial growth factor (VEGF) secretion from vascular wall cells. The increase in the secretion was mediated through protein kinase C (PKC) and mitogen-activated protein kinase (MAPK) signalling pathways. PEth-containing HDL particles were able to increase the VEGF secretion in rats in vivo. Similar effects were also observed when rats were given HDL particles isolated from the plasma of alcoholics. The PEth-induced change in the electrical charge of lipoproteins may affect the binding of lipoproteins to their receptors and binding proteins. The effects of PEth on the secretion of VEGF from the endothelial cells were shown to be mediated through HDL receptor. The changes in HDL particles caused by Phosphatidylethanol may modify the metabolism of lipoproteins and lipid-mediated signalling pathways regulating VEGF in vascular wall cells.
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Phosphatidylethanol mediates its effects on the vascular endothelial growth factor via hdl receptor in endothelial cells
Alcoholism: Clinical and Experimental Research, 2009Co-Authors: Marja K Liisanantti, Markku J SavolainenAbstract:Background: Previous epidemiological studies have shown that light to moderate alcohol consumption has protective effects against coronary heart disease but the mechanisms of the beneficial effect of alcohol are not known. Ethanol may increase high density lipoprotein (HDL) cholesterol concentration, augment the reverse cholesterol transport, or regulate growth factors or adhesion molecules. To study whether qualitative changes in HDL phospholipids mediate part of the beneficial effects of alcohol on atherosclerosis by HDL receptor, we investigated whether Phosphatidylethanol (PEth) in HDL particles affects the secretion of vascular endothelial growth factor (VEGF) by a human scavenger receptor CD36 and LIMPII analog-I (CLA-1)-mediated pathway. Methods: Human EA.hy 926 endothelial cells were incubated in the presence of native HDL or PEth-HDL. VEGF concentration and CLA-1 protein expression were measured. Human CLA-1 receptor-mediated mechanisms in endothelial cells were studied using CLA-1 blocking antibody and protein kinase inhibitors. Results: Phosphatidylethanol-containing HDL particles caused a 6-fold increase in the expression of CLA-1 in endothelial cells compared with the effect of native HDL. That emergent effect was mediated mainly through protein kinase C and p44/42 mitogen-activated protein kinase pathways. PEth increased the secretion of VEGF and that increase could be abolished by a CLA-1 blocking antibody. Conclusions: High density lipoprotein particles containing PEth bind to CLA-1 receptor and thereby increase the secretion of VEGF from endothelial cells. Ethanol-induced protective effects against coronary heart disease may be explained, at least partly, by the effects of PEth-modified HDL particles on VEGF via CLA-1-mediated mechanisms in endothelial cells.
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effects of Phosphatidylethanol on mouse adipocyte differentiation and expression of stearoyl coa desaturase 1
Alcoholism: Clinical and Experimental Research, 2007Co-Authors: Tuija Huusko, Antti Nissinen, Marja K Liisanantti, Sakari Kakko, Eevariitta Savolainen, Jussi Vuoristo, Markku J SavolainenAbstract:BACKGROUND: Phosphatidylethanol (PEth) is an aberrant phospholipid formed in vivo only in the presence of ethanol. In circulation PEth is associated with lipoproteins and is transferred from one lipoprotein to another. Lipoprotein-associated PEth affects endothelial and smooth muscle cells of blood vessels, but its effects on other cell types have not been explored. Adipocytes have a central role in metabolic syndrome and obesity. In this study we tested whether lipoprotein-associated PEth affects stearoyl-CoA desaturase 1 (SCD1) which plays a major role in lipid-mediated signaling in the differentiation of adipocytes. METHODS: Mouse 3T3-L1 preadipocytes were differentiated to adipocytes in the presence of high-density lipoproteins (HDL) isolated from the plasma of healthy volunteers or PEth-containing HDL modified in vitro. After incubation, fat accumulation, SCD1 mRNA expression, SCD1 protein content, and fatty acid composition of adipocytes were determined. RESULTS: Phosphatidylethanol-containing HDL particles inhibited adipocyte differentiation and decreased the 18:1/18:0 ratio of cellular fatty acids by 28% compared with native HDL particles. Moreover, PEth-containing HDL reduced the SCD1 protein content by 39%. CONCLUSIONS: Lipoprotein-associated PEth may mediate the effects of ethanol on SCD1 and differentiation of preadipocytes to adipocytes.
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transfer of Phosphatidylethanol between lipoproteins
Alcoholism: Clinical and Experimental Research, 2004Co-Authors: Marja K Liisanantti, Kimmo Huhta, Markku J SavolainenAbstract:BACKGROUND: Phosphatidylethanol (PEth) is an abnormal phospholipid formed only in the presence of ethanol. It has been recently shown that lipoprotein-associated PEth may mediate the effects of ethanol on endothelial cells, and this may explain, at least in part, the beneficial effect of ethanol on atherosclerosis. This study was performed to investigate the transfer of PEth between lipoproteins and the effects of PEth on cholesteryl ester transfer protein (CETP) activity in plasma. METHODS: Lipoproteins were isolated from the plasma of healthy male volunteers (n = 16) and male alcoholics (n = 13). The transfer of cholesteryl esters and PEth was determined between labeled low-density lipoprotein (LDL) and unlabeled high-density lipoprotein particles in vitro. The electrophoretic mobility of PEth-modified LDL particles was determined by agarose gel electrophoresis. RESULTS: PEth was transferred from PEth-modified LDL to high-density lipoprotein at an initial rate of 25.9 nmol/ml/hr. Monoclonal antibody (TP2) against the putative lipid-binding domain of CETP inhibited the transfer rate of PEth by approximately 64%, whereas the cholesteryl ester transfer was inhibited by 86%. This indicates that most of PEth was transferred by transfer proteins other than CETP. CONCLUSIONS: The transfer of PEth between lipoproteins enables the redistribution of PEth from lipoprotein fractions with a slow turnover to those with a rapid clearance. Moreover, the PEth-induced change in the electrical charge of lipoproteins may affect the binding of lipoproteins to their receptors and binding proteins. This in turn may alter the metabolism of lipoproteins and lipid-mediated signaling pathways in the cells delineating the vascular wall.
