The Experts below are selected from a list of 18570 Experts worldwide ranked by ideXlab platform
David N. Brindley - One of the best experts on this subject based on the ideXlab platform.
-
inhibition of autotaxin production or activity blocks Lysophosphatidylcholine induced migration of human breast cancer and melanoma cells
Molecular Carcinogenesis, 2009Co-Authors: Cristoforo G Gaetano, Nasser Samadi, Jose L Tomsig, Timothy L Macdonald, Kevin R Lynch, David N. BrindleyAbstract:Increased expression of autotaxin is linked to several malignancies including glioblastoma, breast, renal, ovarian, lung and thyroid cancers. Autotaxin promotes metastasis as well as cell growth, survival, and migration of cancer cells. These actions could depend on the non-catalytic effects of autotaxin on cell adhesion, or the catalytic activity of autotaxin, which converts Lysophosphatidylcholine into lysophosphatidate in the extracellular environment. Both Lysophosphatidylcholine and lysophosphatidate have been reported to stimulate migration through their respective G-protein coupled receptors. The present study determines the roles of autotaxin, Lysophosphatidylcholine and lysophosphatidate in controlling the migration two cancer cell lines MDA-MB-231 breast cancer cells, which produce little autotaxin and MDA-MB-435 melanoma cells that secrete significant levels of autotaxin. Lysophosphatidylcholine alone was unable to stimulate the migration of either cell type unless autotaxin was present. Knocking down autotaxin secretion, or inhibiting its catalytic activity, blocked cell migration by preventing lysophosphatidate production and the subsequent activation of LPA1/3 receptors. We conclude that inhibiting autotaxin production or activity of could provide a beneficial adjuvant to chemotherapy for preventing metastasis in patients with high autotaxin expression in their tumors.
-
Hepatic secretion of Lysophosphatidylcholine: A novel transport system for polyunsaturated fatty acids and choline
The Journal of Nutritional Biochemistry, 1993Co-Authors: David N. BrindleyAbstract:Since 1985 it has become clear that perfused liver I and cultured hepatocytes 2 can produce Lysophosphatidylcholine that is secreted into the perfusion, or incubation medium. In the case of perfused livers, this production is about twice as high as the secretion of phosphatidylcholineJ whereas in the hepatocyte system it is about seven times higher. 2 Consequently, the liver has the capacity to produce relatively large amounts of Lysophosphatidylcholine. Lysophosphatidylcholine is bound to albumin in the blood and it is often the second most prevalent phospholipid in plasma. 3 Its concentration remains relatively high even in patients suffering from a deficiency of lecithin:cholesterol acyltransferase (LCAT). 4 These combined observations indicate that the production of Lysophosphatidylcholine by the liver provides a source for this lipid in the blood, in addition to that produced in the circulation by LCAT. Analysis of the composition of Lysophosphatidylcholine that is secreted from perfused liver I and hepatocytes 5,6 indicates that a major portion of the fatty acids are polyunsaturated. It has therefore been proposed that the secretion of Lysophosphatidylcholine by the liver can provide a novel system for the transport of both polyunsaturated fatty acids and choline to other organs. 6,7 In contrast to what has been stated for rat hepatocytes, no significant production of Lysophosphatidylcholine could be detected in the culture medium of ovine hepatocytes. 6 If this proves to be a general finding for ruminant animals, the secretion of Lysophosphatidylcholine from the liver may be restricted to non-ruminants. This article reviews the characteristics of Lysophosphatidylcholine secretion, its regulation, and some pos-
-
Sexual dimorphism in the preferential secretion of unsaturated Lysophosphatidylcholine by rat hepatocytes but no secretion by sheep hepatocytes.
Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1991Co-Authors: Annette Graham, Victor A. Zammit, William W. Christie, David N. BrindleyAbstract:Abstract (1) Rat and ovine hepatocytes were incubated in monolayer culture with various fatty acids to determine their effects on the composition of the Lysophosphatidylcholine that was secreted. (2) No Lysophosphatidylcholine was detected in the medium from the ovine hepatocytes even though these cells were hormonally responsive and they secreted phosphatidylcholine and triacylglycerol in very-low-density lipoprotein. (3) Lysophosphatidylcholine was readily detected in the incubation medium of rat hepatocytes. The predominant fatty acids in this lipid were unsaturated. Stearate and arachidonate contributed 15 and 34%, and 24% and 26% of the total fatty acids when hepatocytes from male and female rats were used, respectively. The relative proportions of stearate and arachidonate in the phosphatidylcholine secreted from the hepatocytes were 20 and 14%, and 28 and 21% for the males and females, respectively. The equivalent values for stearate and arachidonate for phosphatidylcholine in the hepatocytes were 18 and 17% and 33 and 22% for male and female rats. These results provide further indications of sex differences in hepatic phospholipid metabolism and extend this to the secretion of phosphatidylcholine and Lysophosphatidylcholine. (4) The addition of 1 mM stearate to the incubation medium did not significantly decrease the proportion of arachidonate in the Lysophosphatidylcholine obtained from the hepatocytes of the male rats. However, the relative proportion of arachidonate was decreased in incubations that contained 1 mM oleate or linoleate. (5) The results provide evidence that the preferential secretion of unsaturated Lysophosphatidylcholine by the liver may provide a system for transporting unsaturated fatty acids and choline to other organs in non-ruminant animals. However, this mechanism may not operate for ruminats.
Junfen Fu - One of the best experts on this subject based on the ideXlab platform.
-
metformin prevents non alcoholic fatty liver disease in rats role of phospholipase a2 Lysophosphatidylcholine lipoapoptosis pathway in hepatocytes
Chinese journal of pediatrics, 2011Co-Authors: Yao Huang, Junfen FuAbstract:Objective To investigate the potential preventive effects of metformin on non-alcoholic fatty liver disease (NAFLD) and roles of phospholipase A2/Lysophosphatidylcholine pathway in hepatocyte lipoapoptosis in a rat NAFLD model induced by high-fat diet. Method Male SD rats (n=36) were randomly divided into three groups with 12 rats in each and treated with different diet and drugs: group Ⅰ: ordinary diet, group Ⅱ: high-fat diet, group Ⅲ: high-fat diet and metformin. Ten weeks later, the rats were sacrificed and their body weight and liver weight were obtained, serum lipid metabolic indexes, insulin resistance indexes and secretory phospholipase A2(sPLA2), Lysophosphatidylcholine(LPC) levels and other parameters were measured. Phospholipase A2 mRNA expression levels were measured by quantitative reverse transcription-polymerase chain reaction(RT-PCR). In addition, the histological changes of liver tissue were analyzed. Result Compared to ordinary diet group, the rat′s liver weight (g)(16.92±2.49 vs. 12.16±0.82), hepatic exponent(0.034±0.004 vs. 0.026±0.002), serum alanine aminotransferase (U/L)(45.43±9.73 vs. 29.42±6.73), triglyceride(mmol/L)(1.22±0.24 vs. 0.85±0.19), cholesterol(mmol/L)(2.00±0.37 vs. 1.49±0.33), lipoprotein(a)(mmol/L)(743.86±32.19 vs. 648.42±78.87), low-density lipoprotein (mmol/L)(1.31±0.35 vs. 0.65±0.22), insulin(mmol/L)(22.16±5.16 vs. 16.86±5.35), insulin resistance index(5.10±1.45 vs. 3.59±0.99), free fatty acid(mEq/L)(0.57±0.10 vs. 0.35±0.07), sPLA2[μmol/(min·ml)](0.130±0.016 vs. 0.098±0.024), Lysophosphatidylcholine(μmol/L)(707.26±92.48 vs. 508.87±96.50), leptin(pg/ml)(80.08±17.73 vs. 65.11±14.09), liver triglyceride (mg/g)(13.57±0.65 vs. 12.03±1.14), cholesterol (mg/g)(2.19±0.15 vs.1.94±0.12)(P 0.05). Conclusion It was indicated that metformin has potent effects on improving lipid metabolism and insulin resistance in high-fat diet induced non-alcoholic fatty liver disease rat model. The liver protective mechanisms of metformin in non-alcoholic fatty liver disease may be contributed to down-regulation of secretory phospholipase A2 mRNA expression, decrease in serum secretory phospholipase A2, Lysophosphatidylcholine, lower inflammatory response and protect mitochondrial function. Key words: Rats; Fatty liver; Phospholipases A2; Lysophosphatidylcholines
-
Metformin prevents non-alcoholic fatty liver disease in rats: role of phospholipase A2/Lysophosphatidylcholine lipoapoptosis pathway in hepatocytes
Chinese journal of pediatrics, 2011Co-Authors: Yao Huang, Junfen FuAbstract:Objective To investigate the potential preventive effects of metformin on non-alcoholic fatty liver disease (NAFLD) and roles of phospholipase A2/Lysophosphatidylcholine pathway in hepatocyte lipoapoptosis in a rat NAFLD model induced by high-fat diet. Method Male SD rats (n=36) were randomly divided into three groups with 12 rats in each and treated with different diet and drugs: group Ⅰ: ordinary diet, group Ⅱ: high-fat diet, group Ⅲ: high-fat diet and metformin. Ten weeks later, the rats were sacrificed and their body weight and liver weight were obtained, serum lipid metabolic indexes, insulin resistance indexes and secretory phospholipase A2(sPLA2), Lysophosphatidylcholine(LPC) levels and other parameters were measured. Phospholipase A2 mRNA expression levels were measured by quantitative reverse transcription-polymerase chain reaction(RT-PCR). In addition, the histological changes of liver tissue were analyzed. Result Compared to ordinary diet group, the rat′s liver weight (g)(16.92±2.49 vs. 12.16±0.82), hepatic exponent(0.034±0.004 vs. 0.026±0.002), serum alanine aminotransferase (U/L)(45.43±9.73 vs. 29.42±6.73), triglyceride(mmol/L)(1.22±0.24 vs. 0.85±0.19), cholesterol(mmol/L)(2.00±0.37 vs. 1.49±0.33), lipoprotein(a)(mmol/L)(743.86±32.19 vs. 648.42±78.87), low-density lipoprotein (mmol/L)(1.31±0.35 vs. 0.65±0.22), insulin(mmol/L)(22.16±5.16 vs. 16.86±5.35), insulin resistance index(5.10±1.45 vs. 3.59±0.99), free fatty acid(mEq/L)(0.57±0.10 vs. 0.35±0.07), sPLA2[μmol/(min·ml)](0.130±0.016 vs. 0.098±0.024), Lysophosphatidylcholine(μmol/L)(707.26±92.48 vs. 508.87±96.50), leptin(pg/ml)(80.08±17.73 vs. 65.11±14.09), liver triglyceride (mg/g)(13.57±0.65 vs. 12.03±1.14), cholesterol (mg/g)(2.19±0.15 vs.1.94±0.12)(P 0.05). Conclusion It was indicated that metformin has potent effects on improving lipid metabolism and insulin resistance in high-fat diet induced non-alcoholic fatty liver disease rat model. The liver protective mechanisms of metformin in non-alcoholic fatty liver disease may be contributed to down-regulation of secretory phospholipase A2 mRNA expression, decrease in serum secretory phospholipase A2, Lysophosphatidylcholine, lower inflammatory response and protect mitochondrial function. Key words: Rats; Fatty liver; Phospholipases A2; Lysophosphatidylcholines
Knud Kragballe - One of the best experts on this subject based on the ideXlab platform.
-
intracutaneous injection of Lysophosphatidylcholine induces skin inflammation and accumulation of leukocytes
Acta Dermato-venereologica, 2000Co-Authors: A K Ryborg, Bent Deleuran, H Sogaard, Knud KragballeAbstract:Various cell stimuli act through activation of phospholipase A2, which hydrolyses fatty acids from membrane phospholipids, resulting in the formation of fatty acids and lysophospholipids. One of the lysophospholipid classes, Lysophosphatidylcholine, is a chemoattractant for monocytes and T-lymphocytes and induces the expression of adhesion molecules on cultured endothelial cells. The purpose of the present study was to determine whether Lysophosphatidylcholine possesses proinflammatory properties in vivo. This was assessed clinically and histologically by intracutaneous injection of 200-800 nmol Lysophosphatidylcholine in healthy volunteers. Lysophosphatidylcholine elicited a dose- and time-dependent local erythema and oedema. The erythema disappeared within 4 h, while the induration lasted for up to 48 h. HE-stained biopsies taken after 24 h showed a leukocytoclastic vasculitis in 2 of the 6 subjects. Microscopic examination of immunohistochemically stained biopsies taken 24 h after the injection showed a significant increase in the number of T-lymphocytes, monocytes and neutrophils, whereas the number of Langerhans' cells was unchanged after Lysophosphatidylcholine injection. In addition, the number of intercellular cell adhesion molecule-1 and -3-positive cells was increased approximately 3-fold after injection of Lysophosphatidylcholine. In conclusion, the phospholipase A2 hydrolysis product Lysophosphatidylcholine can induce erythema, oedema, a mixed cellular infiltrate and the expression of adhesion molecules.
-
Increased Lysophosphatidylcholine content in lesional psoriatic skin.
British Journal of Dermatology, 1995Co-Authors: Ane Kaltoft Ryborg, B. GrØn, Knud KragballeAbstract:Summary Various cell stimuli occur via activation of phospholipase A2, which hydrolyses polyunsaturated fatty acids from the sn-2 position of membrane phospholipids, resulting in the formation of polyunsaturated fatty acids and lysophospholipids. The level of lysophospholipids is determined by the balance between phospholipase A2 activity and the rate of catabolism of the lysophospholipids. One of the lysophospholipid classes, Lysophosphatidylcholine, has been shown to stimulate certain leucocyte activities which are of importance for the induction and maintenance of inflammation. In addition, it has been demonstrated that phospholipase A2 activity is increased in psoriatic skin. In the present study, we analysed the levels of Lysophosphatidylcholine, by thin layer chromatography, in lesional psoriatic skin, uninvolved psoriatic skin and normal skin. The Lysophosphatidylcholine content, expressed as μmol Lysophosphatidylcholine/μmol phosphatidylcholine, was 1.55, 0.21 and 0.12% in lesional psoriatic skin, uninvolved psoriatic skin and normal skin, respectively. The level of Lysophosphatidylcholine was significantly elevated in lesional compared with uninvolved psoriatic skin (P= 0.004) and normal skin (P= 0.002). The increased Lysophosphatidylcholine levels in psoriatic skin indicate that the phospholipase A2 activation is not accompanied by a corresponding increase in the activity of enzymes catabolizing lysoPC. If present in biologically active concentrations, Lysophosphatidylcholine may contribute to the induction and maintenance of the inflammatory and immunological processes occurring in lesional psoriatic skin.
Yao Huang - One of the best experts on this subject based on the ideXlab platform.
-
metformin prevents non alcoholic fatty liver disease in rats role of phospholipase a2 Lysophosphatidylcholine lipoapoptosis pathway in hepatocytes
Chinese journal of pediatrics, 2011Co-Authors: Yao Huang, Junfen FuAbstract:Objective To investigate the potential preventive effects of metformin on non-alcoholic fatty liver disease (NAFLD) and roles of phospholipase A2/Lysophosphatidylcholine pathway in hepatocyte lipoapoptosis in a rat NAFLD model induced by high-fat diet. Method Male SD rats (n=36) were randomly divided into three groups with 12 rats in each and treated with different diet and drugs: group Ⅰ: ordinary diet, group Ⅱ: high-fat diet, group Ⅲ: high-fat diet and metformin. Ten weeks later, the rats were sacrificed and their body weight and liver weight were obtained, serum lipid metabolic indexes, insulin resistance indexes and secretory phospholipase A2(sPLA2), Lysophosphatidylcholine(LPC) levels and other parameters were measured. Phospholipase A2 mRNA expression levels were measured by quantitative reverse transcription-polymerase chain reaction(RT-PCR). In addition, the histological changes of liver tissue were analyzed. Result Compared to ordinary diet group, the rat′s liver weight (g)(16.92±2.49 vs. 12.16±0.82), hepatic exponent(0.034±0.004 vs. 0.026±0.002), serum alanine aminotransferase (U/L)(45.43±9.73 vs. 29.42±6.73), triglyceride(mmol/L)(1.22±0.24 vs. 0.85±0.19), cholesterol(mmol/L)(2.00±0.37 vs. 1.49±0.33), lipoprotein(a)(mmol/L)(743.86±32.19 vs. 648.42±78.87), low-density lipoprotein (mmol/L)(1.31±0.35 vs. 0.65±0.22), insulin(mmol/L)(22.16±5.16 vs. 16.86±5.35), insulin resistance index(5.10±1.45 vs. 3.59±0.99), free fatty acid(mEq/L)(0.57±0.10 vs. 0.35±0.07), sPLA2[μmol/(min·ml)](0.130±0.016 vs. 0.098±0.024), Lysophosphatidylcholine(μmol/L)(707.26±92.48 vs. 508.87±96.50), leptin(pg/ml)(80.08±17.73 vs. 65.11±14.09), liver triglyceride (mg/g)(13.57±0.65 vs. 12.03±1.14), cholesterol (mg/g)(2.19±0.15 vs.1.94±0.12)(P 0.05). Conclusion It was indicated that metformin has potent effects on improving lipid metabolism and insulin resistance in high-fat diet induced non-alcoholic fatty liver disease rat model. The liver protective mechanisms of metformin in non-alcoholic fatty liver disease may be contributed to down-regulation of secretory phospholipase A2 mRNA expression, decrease in serum secretory phospholipase A2, Lysophosphatidylcholine, lower inflammatory response and protect mitochondrial function. Key words: Rats; Fatty liver; Phospholipases A2; Lysophosphatidylcholines
-
Metformin prevents non-alcoholic fatty liver disease in rats: role of phospholipase A2/Lysophosphatidylcholine lipoapoptosis pathway in hepatocytes
Chinese journal of pediatrics, 2011Co-Authors: Yao Huang, Junfen FuAbstract:Objective To investigate the potential preventive effects of metformin on non-alcoholic fatty liver disease (NAFLD) and roles of phospholipase A2/Lysophosphatidylcholine pathway in hepatocyte lipoapoptosis in a rat NAFLD model induced by high-fat diet. Method Male SD rats (n=36) were randomly divided into three groups with 12 rats in each and treated with different diet and drugs: group Ⅰ: ordinary diet, group Ⅱ: high-fat diet, group Ⅲ: high-fat diet and metformin. Ten weeks later, the rats were sacrificed and their body weight and liver weight were obtained, serum lipid metabolic indexes, insulin resistance indexes and secretory phospholipase A2(sPLA2), Lysophosphatidylcholine(LPC) levels and other parameters were measured. Phospholipase A2 mRNA expression levels were measured by quantitative reverse transcription-polymerase chain reaction(RT-PCR). In addition, the histological changes of liver tissue were analyzed. Result Compared to ordinary diet group, the rat′s liver weight (g)(16.92±2.49 vs. 12.16±0.82), hepatic exponent(0.034±0.004 vs. 0.026±0.002), serum alanine aminotransferase (U/L)(45.43±9.73 vs. 29.42±6.73), triglyceride(mmol/L)(1.22±0.24 vs. 0.85±0.19), cholesterol(mmol/L)(2.00±0.37 vs. 1.49±0.33), lipoprotein(a)(mmol/L)(743.86±32.19 vs. 648.42±78.87), low-density lipoprotein (mmol/L)(1.31±0.35 vs. 0.65±0.22), insulin(mmol/L)(22.16±5.16 vs. 16.86±5.35), insulin resistance index(5.10±1.45 vs. 3.59±0.99), free fatty acid(mEq/L)(0.57±0.10 vs. 0.35±0.07), sPLA2[μmol/(min·ml)](0.130±0.016 vs. 0.098±0.024), Lysophosphatidylcholine(μmol/L)(707.26±92.48 vs. 508.87±96.50), leptin(pg/ml)(80.08±17.73 vs. 65.11±14.09), liver triglyceride (mg/g)(13.57±0.65 vs. 12.03±1.14), cholesterol (mg/g)(2.19±0.15 vs.1.94±0.12)(P 0.05). Conclusion It was indicated that metformin has potent effects on improving lipid metabolism and insulin resistance in high-fat diet induced non-alcoholic fatty liver disease rat model. The liver protective mechanisms of metformin in non-alcoholic fatty liver disease may be contributed to down-regulation of secretory phospholipase A2 mRNA expression, decrease in serum secretory phospholipase A2, Lysophosphatidylcholine, lower inflammatory response and protect mitochondrial function. Key words: Rats; Fatty liver; Phospholipases A2; Lysophosphatidylcholines
J.d. Bell - One of the best experts on this subject based on the ideXlab platform.
-
Formation of Transient Non-Protein Calcium Pores by Lysophospholipids in S49Lymphoma cells
The Journal of Membrane Biology, 2004Co-Authors: H.a. Wilson-ashworth, A.m. Judd, B.d. Freestone, S. Taylor, M.k. Mizukawa, K.r. Cromar, S. Sudweeks, J.d. BellAbstract:Palmitoyl-Lysophosphatidylcholine promotes a transient calcium influx in lymphoma cells. Previously, it was observed that this influx was accompanied by a temporary increase in propidium iodide permeability that appeared linked to calcium entry. Those studies demonstrated that cobalt or nickel could block the response to Lysophosphatidylcholine and raised the question of whether the calcium conductance involved specific channels. This communication describes a series of experiments to address that issue. The time dependence and structural specificity of the responses to Lysophosphatidylcholine reinforced the hypothesis of a specific channel or transporter. Nevertheless, observations using patch clamp or calcium channel blockers suggested that this “channel” does not involve proteins. Alternative protein-mediated mechanisms such as indirect involvement of the sodium-calcium exchanger and the sodium-potassium ATPase were also excluded. Experiments with extracellular and intracellular calcium chelators suggested a common route of entry for calcium and propidium iodide. More directly, the ability of Lysophosphatidylcholine to produce cobalt-sensitive permeability to propidium iodide was reproduced in protein-free artificial membranes. Finally, the transient nature of the calcium time course was rationalized quantitatively by the kinetics of Lysophosphatidylcholine metabolism. These results suggest that physiological concentrations of Lysophosphatidylcholine can directly produce membrane pores that mimic some of the properties of specific protein channels.
