Disease relevance of LMGP01050043

• Here we show that administration of lysophosphatidylcholine (LPC), an endogenous lysophospholipid, protected mice against lethality after cecal ligation and puncture (CLP) or intraperitoneal injection of Escherichia coli [1].
• Therapeutic effects of lysophosphatidylcholine in experimental sepsis [1].
• Although the biological actions of the cell membrane and serum lipid lysophosphatidylcholine (LPC) in atherosclerosis and systemic autoimmune disease are well recognized, LPC has not been linked to a specific cell-surface receptor [2].
• Ischemia increased BLM lysophosphatidylcholine (1.3 vs. 2.5%, P less than 0.05) and phosphatidic acid (0.4 vs. 1.3%, P less than 0.05) [3].
• Lysophosphatidylcholine (lysoPC), a component of atherogenic lipoproteins and atherosclerotic lesions, has been recently suggested to play a role in atherogenesis [4].

Psychiatry related information on LMGP01050043

• Lysophosphatidylcholine decreases locomotor activities and dopamine turnover rate in rats [5].
• To understand the mechanism(s) of hypercholesterolemia-induced erectile dysfunction, we studied the effect of lysophosphatidylcholine (LPC) on the membrane conductance of corporal smooth muscle cells [6].
• Lysophosphatidylcholine-induced lysis of erythrocytes in Duchenne and myotonic dystrophies and in Huntington's disease [7].

High impact information on LMGP01050043

• Further analysis showed that lysophosphatidylcholine was released from apoptotic cells due to the caspase-3 mediated activation of the calcium-independent phospholipase A(2) [8].
• We report here that binding of CRP to model membranes of PC requires the incorporation into the bilayer of lysophosphatidylcholine (LPC) [9].
• Lysophosphatidylcholine as a ligand for the immunoregulatory receptor G2A [2].
• The methylation of phospholipids is coupled to Ca2+ influx and the release of arachidonic acid, lysophosphatidylcholine, and prostaglandins [10].
• Infusion of lysophosphatidylcholine, a component of oxidized low density lipoprotein, markedly decreased apoptotic cell clearance in gld mice, indicating that hypercholesterolemia promotes autoimmune disease in this background [11].

Chemical compound and disease context of LMGP01050043

• Ischemia also decreased BBM sphingomyelin (38.5 vs. 29.6%, P less than 0.01) and phosphatidylserine (16.1 vs. 11.4%, P less than 0.01), and increased phosphatidylcholine (17.2 vs. 29.7%, P less than 0.01), phosphatidylinositol (1.8 vs. 4.6%, P less than 0.01), and lysophosphatidylcholine (1.0 vs. 1.8%, P less than 0.05) [3].
• Because the liver plays a key role in plasma lysophosphatidylcholine removal and biotransformation and because virtually nothing is known of these processes in a diseased organ, the hepatobiliary metabolism of lysophosphatidylcholine was investigated in rats with carbon tetrachloride-induced liver cirrhosis [12].
• Delayed afterdepolarizations induced by LPC (75 microM) and epinephrine (10(-6) M) persisted even in the presence of acidosis (pH 6.7) and hyperkalemia ([K+]o = 7 mM) [13].
• Autotaxin is overexpressed in glioblastoma multiforme and contributes to cell motility of glioblastoma by converting lysophosphatidylcholine to lysophosphatidic acid [14].
• Here we show that certain LPLs, particularly lysophosphatidylcholine and lysophosphatidylinositol, prevent neuronal death both in an in vivo model of transient global ischemia and in an in vitro model of excitotoxicity using primary cultures of cerebellar granule cells exposed to high extracellular concentrations of glutamate (20-40 micromol/L) [15].

Biological context of LMGP01050043

• I-PLA(2) activation during apoptosis promotes the exposure of membrane lysophosphatidylcholine leading to binding by natural immunoglobulin M antibodies and complement activation [16].
• Influence of lysophosphatidylcholine on the C-apolipoprotein content of rat and human triglyceride-rich lipoproteins during triglyceride hydrolysis [17].
• Lysophosphatidylcholine transcriptionally induces growth factor gene expression in cultured human endothelial cells [18].
• However, to determine whether compartmentalization is critical, intracellular pressure microinjection of LPC was performed with simultaneous recording of the transmembrane action potential [19].
• Elevated phosphatidylcholine and reduced lysophosphatidylcholine fractions indicated impairment of cholesterol esterification by lecithin-cholesterol acyltransferase [20].

Anatomical context of LMGP01050043

• Role of lysophosphatidylcholine in the inhibition of endothelial cell motility by oxidized low density lipoprotein [21].
• Lysophosphatidylcholine is a major phospholipid component of Ox-LDL and is known to be chemotactic for monocytes [22].
• We examined the effects of lysophosphatidylcholine (LPC) in isolated guinea pig ventricular myocytes [23].
• We show that lysophosphatidylcholine is also chemotactic for T lymphocytes with a maximal fourfold increase at 10 microM [22].
• Induction of cyclooxygenase-2 in human umbilical vein endothelial cells by lysophosphatidylcholine [4].

Associations of LMGP01050043 with other chemical compounds

• First, lesion LDL showed many of the physical and chemical properties of oxidized LDL, properties that differ from those of plasma LDL: higher electrophoretic mobility, a higher density, higher free cholesterol content, and a higher proportion of sphingomyelin and lysophosphatidylcholine in the phospholipid fraction [24].
• METHODS: CaCo-2 cells cultured on semipermeable supports were incubated with taurocholate and lysophosphatidylcholine, and cholesterol synthesis rate, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity, mass, and messenger RNA abundance were estimated [25].
• This receptor displays a distinct structure-activity relationship: it requires an unsubstituted amino group because N-acetyl-SPC, lysophosphatidic acid and lysophosphatidylcholine were inactive [26].
• The lacking H+ efflux could be restored (1) by adding lysophosphatidylcholine (LPC), a product of PLA2 activity, to vacuoles in situ and (2) by exposing intact cells to isotonic, near-neutral HEPES buffers [27].
• An increase in lysophosphatidylcholine and a decrease in phosphatidylethanolamine contents were observed in membranes isolated from diabetic rats [28].

Gene context of LMGP01050043

• We have examined the effect of lysophosphatidylcholine (lyso-PC; lysolecithin), a major phospholipid component of atherogenic lipoproteins, on the expression of adhesion molecules for monocytes, such as vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), in cultured human and rabbit arterial endothelial cells [29].
• Purified PON-1 hydrolyzed phosphatidylcholine core aldehydes to lysophosphatidylcholine [30].
• G2A is a proton-sensing G-protein-coupled receptor antagonized by lysophosphatidylcholine [31].
• Lysophosphatidylcholine stimulates activator protein 1 and the c-Jun N-terminal kinase activity [32].
• This study is the first to demonstrate that PLD2 activity is up-regulated by Ca2+ influx and that cPLA2 may play a key role in the Ca2+-dependent regulation of PLD2 through generation of lysophosphatidylcholine [33].

Analytical, diagnostic and therapeutic context of LMGP01050043

• Changes in membrane intrinsic curvature induced by the external addition of lysophosphatidylcholine (LPC) generated massive spectroscopic changes in the narrow constriction that forms the channel 'gate', trapping the channel in the fully open state [34].
• To elucidate possible mechanisms of lysophosphatidylcholine-induced depolarization, we investigated the effects of lysophosphatidylcholine on the electrophysiological properties of cat ventricular muscle, using potassium ion-selective electrodes and conventional microelectrode, current-, and voltage-clamp techniques [35].
• Depolarizing concentrations of lysophosphatidylcholine did not reduce the potassium equilibrium potential, as determined from the reversal potential of the time-dependent potassium current and measurements of intracellular potassium activity using potassium ion-selective electrodes [35].
• Bioassay experiments showed that lysophosphatidylcholine inhibited the production and/or release of endothelium-derived relaxing factor from cultured endothelial cells [36].
• Lysophosphatidylcholine perfusion reversed the control patterns of absorption and produced water exsorption, produced an efflux of protein into the perfusate and increased beta-glucuronidase activity [37].

References