Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.1.34 (lipoprotein lipase)
7,025 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Follicle-stimulating hormone (FSH) is a glycoprotein that transmits its signals via a G protein-coupled receptor. As yet, not many targets of FSH have been identified, able to justify the critical role of this hormone on reproductive events. On the other hand, among the biological activities of the endocannabinoid anandamide (AEA), growing interest has been attracted by the regulation of mammalian fertility. Recently, we have shown that treatment of mouse primary Sertoli cells with FSH enhances the activity of the AEA hydrolase (fatty acid amide hydrolase, FAAH), whereas it does not affect the enzymes that synthesize AEA, nor the level of the AEA-binding type-2 cannabinoid and type-1 vanilloid receptors. In addition, diacylglycerol lipase and monoacylglycerol lipase, which, respectively, synthesize and degrade the other major endocannabinoid 2-arachidonoylglycerol, were not regulated by FSH. Interestingly, FAAH stimulation by FSH occurred through protein kinase A and aromatase-dependent pathways that were able to modulate FAAH activity (via phosphorylation of accessory proteins) and faah gene expression (via an estrogen response element on the promoter region). Taken together, these data identify FAAH as the only target of FSH among the elements of the endocannabinoid system, with a critical impact on Sertoli cell proliferation, and thus spermatogenesis and male reproduction.
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PMID:Modulation of the endocannabinoid-degrading enzyme fatty acid amide hydrolase by follicle-stimulating hormone. 1964 15

In this study, phosphatidic acid (PA) metabolization is found to generate diacylglycerol (DAG), monoacylglycerol (MAG) and glycerol by the sequential action of lipid phosphate phosphatase (LPP), diacylglycerol lipase (DAGL), and monoacylglycerol lipase (MAGL) in cerebral cortex (CC) synaptosomes. It is also demonstrated that PA is metabolized by phospholipases A (PLA)/lysophosphatidic acid phosphohydrolase (LPAPase) in synaptic endings. Age-related changes in the metabolization of PA have been observed in rat cerebral cortex synaptosomes in the presence of the alternative substrates for LPP, namely LPA, sphingosine 1-phosphate (S1P) and ceramide 1-phosphate (C1P). In addition, LPA and C1P up to concentrations of about 50 microM favor the metabolism in the direction of MAG and glycerol in aged and adult synaptosomes, respectively. At equimolecular concentrations with PA, LPA decreases DAG formation in adult and aged synaptosomes, whereas S1P decreases it and C1P increases it only in aged synaptosomes. Sphingosine (50 microM) or ceramide (100 microM) increase PA metabolism by the pathway that involves LPP/DAGL/MAGL action in aged membranes. Using RHC-80267, a DAGL inhibitor, we could observe that 50% and 33% of MAG are produced as a result of DAGL action in adult and aged synaptosomes, respectively. Taken together, our findings indicate that the ageing modifies the different enzymatic pathways involved in PA metabolization.
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PMID:Age-related changes in the metabolization of phosphatidic acid in rat cerebral cortex synaptosomes. 1969 Nov 45

Endocannabinoids have been implicated in the regulation of consumption of palatable food, sugar in particular. In this study, we investigated how palatable solutions would affect the hypothalamic mRNA expression of enzymes involved in the synthesis and degradation of the two main endocannabinoids, anandamide and 2-arachidonoyl-glycerol. Rats were offered sugar solutions to drink for one week, during which daily food and drink intake, and body weight gain was monitored. Rats offered sugar solutions to drink consumed less solid food but drank more of their respective sugar solution than did water-drinking control rats, resulting in increased total calorie intake. However, this increase in caloric intake did not result in increased body weight or adiposity in the rats. The mRNA expression of fatty acid amid hydrolase was up-regulated by sucrose and fructose. N-acyl phospatidyl ethanolamine phospholipase D mRNA was up-regulated by sucrose, whereas phospholipase C was down-regulated by all forms of sugar tested. The mRNA expression of monoglyceride lipase was down-regulated by all three forms of sugar. Also, the mRNA expression of diacylglycerol lipase 1alpha was down-regulated by sucrose and fructose, whereas the mRNA expression of diacylglycerol lipase 1beta was up-regulated by fructose. In this study, we show that sugars in liquid form affect enzymes involved in the degradation and synthesis of endocannabinoids in the hypothalamus and that this effect predates obesity.
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PMID:Fructose affects enzymes involved in the synthesis and degradation of hypothalamic endocannabinoids. 2008 90

We investigated the involvement of basal sympathetic tone in brown adipose tissue (BAT) recruitment and gene expression profile induced by peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activation. Innervated and surgically denervated BAT pads of rats treated or not with rosiglitazone (15 mg.kg(-1).day(-1), 7 days) were evaluated for weight, triacylglycerol (TAG) and DNA content, mitochondrial mass, and gene expression. Rosiglitazone induced BAT recruitment (increased mass, TAG and DNA content) and mRNA levels of lipolytic (adipose tissue triglyceride lipase and CGI58) and lipogenic (lipoprotein lipase, phosphoenolpyruvate carboxykinase, fatty acid binding protein 4, and diacylglycerol acyltransferase 1) proteins independently of tissue innervation status. Mitochondrial mass and mRNA levels of its regulators peroxisome proliferator-activated receptor coactivator-alpha and CCAAT/enhancer binding protein-beta were not affected by rosiglitazone, while being significantly reduced by denervation. By contrast, maximal stimulation of uncoupling protein 1 (UCP1) (thermogenesis), cell death-inducing DNA fragmentation factor-45-like effector A (inhibitor of UCP1 activity), monoacylglycerol lipase (lipolysis), small heterodimer partner (transcription), and glycerokinase (TAG synthesis) by rosiglitazone depended on the presence of intact BAT innervation. Cold exposure (5 degrees C, 24 h) significantly increased UCP1 mRNA levels in innervated BAT pads of untreated rats, without affecting the already high BAT UCP1 levels of rosiglitazone-treated animals. A similar pattern of response was found in denervated pads, but with markedly lower UCP1 expression than that in innervated BAT. In conclusion, whereas the mass (hyperplasia and hypertrophy), lipogenic, and lipolytic components of BAT recruitment induced by rosiglitazone occur independently of tissue sympathetic innervation, maximal UCP1 expression induced by PPAR-gamma in vivo depends on the presence of basal BAT adrenergic tone. The residual sympathetic tone found under rosiglitazone treatment is, therefore, involved in the modulation of a subset of major components of PPAR-gamma-mediated BAT recruitment.
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PMID:Basal adrenergic tone is required for maximal stimulation of rat brown adipose tissue UCP1 expression by chronic PPAR-gamma activation. 2039 57

Rearing rats in single cages from weaning until adulthood (social isolation) produces a number of behavioral and neurochemical alterations similar to those observed in psychoses such as schizophrenia. Also, a dysregulation of the endocannabinoid system has been implicated in schizophrenia. The aim of this study was to examine the effect of social isolation on changes to mRNA expression of 1) the cannabinoid receptor CB(1), 2) enzymes responsible for the synthesis of the endocannabinoids anandamide (N-acyl phosphatidylethanolamine-phospholipase D or NAPE-PLD) and 2-arachidonoyl-glycerol or 2-AG (diacylglycerol lipase or DAGL isozymes alpha and beta) and 3) enzymes that degrade endocannabinoids (fatty acid amide hydrolase/FAAH for anandamide, and monoacylglycerol lipase/MAGL for 2-AG). Twenty-one-day post natal rats were randomly housed individually, or in groups of 6, for 8 weeks. CB(1) receptor, DAGL(alpha) and DAGLbeta, MAGL and FAAH mRNA levels were measured in the brains using in situ hybridization histochemistry. CB(1) receptor, DAGL(alpha), DAGLbeta, MAGL and NAPE-PLD mRNA expression levels were significantly higher in a number of brain regions from socially isolated rats; particularly in the prefrontal regions, cortical layers and a number of thalamic regions. DAGLbeta mRNA was significantly higher in the substantia nigra and ventral tegmental area. FAAH mRNA expression was significantly lower in a number of prefrontal regions, the cortical layers and in the caudate putamen and other associated areas of socially isolated rats. Such differences in endocannabinoid system mRNA in brains of socially isolated rats compared to normal rats further supports the potential importance of the endocannabinoid system in psychotic disease states.
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PMID:The effect of social isolation on rat brain expression of genes associated with endocannabinoid signaling. 2043 15

Membranes are known to respond rapidly to various environmental perturbations by changing their composition and microdomain organization. In previous work we showed that a membrane fluidizer benzyl alcohol (BA) could mimic the effects of heat stress and enhance heat shock protein synthesis in different mammalian cells. Here we explore heat- and BA-induced stress further by characterizing stress-induced membrane lipid changes in mouse melanoma B16 cells. Lipidomic fingerprints revealed that membrane stress achieved either by heat or BA resulted in pronounced and highly specific alterations in lipid metabolism. The loss in polyenes with the concomitant increase in saturated lipid species was shown to be a consequence of the activation of phopholipases (mainly phopholipase A(2) and C). A phospholipase C-diacylglycerol lipase-monoacylglycerol lipase pathway was identified in B16 cells and contributed significantly to the production of several lipid mediators upon stress including the potent heat shock modulator, arachidonic acid. The accumulation of cholesterol, ceramide and saturated phosphoglyceride species with raft-forming properties observed upon both heat and BA treatments of B16 cells may explain the condensation of ordered plasma membrane domains previously detected by fluorescence microscopy and may serve as a signalling platform in stress responses or as a primary defence mechanism against the noxious effects of stresses.
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PMID:Lipidomics reveals membrane lipid remodelling and release of potential lipid mediators during early stress responses in a murine melanoma cell line. 2043 Jan 10

In this study, we have ascertained the presence and functionality in mouse embryonic stem cells (ESCs) of members of the endocannabinoid system that have been proposed as possible modulators of the survival and differentiation of various type of stem cells. We show that mouse ESCs, in addition to classical CB(1) and CB(2) cannabinoid receptors, express the transient receptor potential vanilloid receptor, at mRNA, protein, and binding levels. Remarkably, we demonstrate that ESCs have the mRNA, protein, and enzyme activity to synthesize and degrade the prominent endocannabinoids anandamide (through N-acyl-phosphatidylethanolamine-specific phospholipase D and fatty acid amide hydrolase) and 2-arachidonoylglycerol (through diacylglycerol lipase and monoacylglycerol lipase). In addition, both endocannabinoids were detected in ESCs that were also shown to constitutively release a fatty acid amide hydrolase-activating compound. Finally, we document that the stimulation of ESCs by methanandamide, a nonhydrolysable analog of anandamide, does not lead to overt alteration of the expression of Oct3/4, Nanog, and Cdx2, genes that are involved in early cell fate in the preimplantation embryo and stemness, or of the expression patterns of Brachyury and Hnf4, genes that are used as late markers of lineage differentiation capability of ESC-derived embryoid bodies. Similarly ineffective on the expression of the tested stemness genes was 2-arachidonoylglycerol. Taken together, these results confirm and extend the notion that ESCs express several functional members of the endocannabinoid system, but they leave open the question about their role in stem cells as modulators of stemness and differentiation potential.
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PMID:Characterization of the endocannabinoid system in mouse embryonic stem cells. 2044 14

N-methyl-D-aspartate (NMDA) has been implicated in the regulation of several autonomic responses in the brain. The present study determined whether activation of alpha1-adrenoceptors is involved in the centrally administered NMDA-induced adrenomedullary catecholamine outflow, using urethane-anesthetized rats. The NMDA (5.0 nmol/animal, i.c.v.)-induced elevation of plasma levels of noradrenaline and adrenaline was reduced by phentolamine (0.33 micromol/animal, i.c.v.), a non-selective alpha-adrenoceptor antagonist, and by 2-{[b-(4-hydroxyphenyl)ethyl]aminomethyl}-1 tetralone (HEAT) (90.0 nmol/animal, i.c.v.), a selective alpha1-adrenoceptor antagonist. In contrast, sotalol (0.8 micromol/animal, i.c.v.), a non-selective beta-adrenoceptor antagonist, did not alter the responses. In addition, U-73122, a phospholipase C inhibitor (5.0 nmol/animal, i.c.v.), RHC-80267, a diacylglycerol lipase inhibitor (1.3 micromol/animal, i.c.v.) and URB 602, a monoacylglycerol lipase inhibitor (0.85 and 1.7 micromol/animal, i.c.v.), reduced the NMDA-induced plasma elevation of both catecholamines. Furthermore, perfusion of the hypothalamic paraventricular nucleus with NMDA (0.3 and 1.0 mM) dose-dependently elevated both noradrenaline levels in the hypothalamic paraventricular nucleus and plasma catecholamine levels. These responses were abolished by co-administration of dizocilpine malate (MK-801, 0.1 mM), a selective non-competitive antagonist of the NMDA receptor and by co-administration of (+)-S-145 (2.5 mM), a selective competitive antagonist of the thromboxane A2 receptor. These results suggest that activation of central alpha1-adrenoceptors is involved in the centrally administered NMDA-induced activation of adrenomedullary catecholamine outflow in rats. Furthermore, signaling cascades downstream of the alpha1-adrenoceptor in the hypothalamic paraventricular nucleus may play an important role in the process.
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PMID:Alpha1-adrenoceptor activation is involved in the central N-methyl-D-aspartate-induced adrenomedullary outflow in rats. 2045 Sep 8

We previously reported that intracerebroventricularly (i.c.v.) administered corticotropin-releasing factor (CRF) (0.5-3.0 nmol/animal) dose-dependently elevates plasma noradrenaline and adrenaline through brain phospholipase C-, diacylglycerol lipase- and prostanoids-mediated mechanisms in rats. Diacylglycerol produced by phospholipase C from phospholipids can be hydrolyzed by diacylglycerol lipase into 2-arachidonoylglycerol, which may be further hydrolyzed by monoacylglycerol lipase into arachidonic acid, a precursor of prostanoids. Recently, 2-arachidonoylglycerol has been recognized as a major brain endocannabinoid, which can modulate synaptic transmission through presynaptic cannabinoid CB(1) receptors. Released 2-arachidonoylglycerol is rapidly deactivated by uptake into cells and enzymatic hydrolysis. In the present study, therefore, we examined (1) the involvement of brain 2-arachidonoylglycerol, (2) the regulatory role of 2-arachidonoylglycerol as a brain endocannabinoid, and (3) the effect of exogenous cannabinoid receptor agonist, on the CRF-induced elevation of plasma noradrenaline and adrenaline using anesthetized rats. The elevation of both catecholamines induced by a submaximal dose of CRF (1.5 nmol/animal, i.c.v.) was reduced by i.c.v. administered MAFP (monoacylglycerol lipase inhibitor) (0.7 and 1.4 micromol/animal), AM 404 (endocannabinoid uptake-inhibitor) (80 and 250 nmol/animal) and ACEA (cannabinoid CB(1) receptor agonist) (0.7 and 1.4 micromol/animal), while AM 251 (cannabinoid CB(1) receptor antagonist) (90 and 180 nmol/animal, i.c.v.) potentiated the response induced by a small dose of CRF (0.5 nmol/animal, i.c.v.). These results suggest a possibility that 2-arachidonoylglycerol is endogenously generated in the brain during CRF-induced activation of central sympatho-adrenomedullary outflow, thereby inhibiting the peptide-induced response by activation of brain cannabinoid CB(1) receptors in anesthetized rats.
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PMID:Possible inhibitory roles of endogenous 2-arachidonoylglycerol during corticotropin-releasing factor-induced activation of central sympatho-adrenomedullary outflow in anesthetized rats. 2051 39

Cannabinoid receptors and their ligands constitute an endogenous signaling system that is found throughout the body, including the eye. This system can be activated by Delta(9)-tetrahydrocannabinol, a major drug of abuse. Cannabinoids offer considerable therapeutic potential in modulating ocular immune and inflammatory responses and in regulating intraocular pressure. The location of cannabinoid receptor 1 (CB(1)) in the retina is known, but recently a constellation of proteins has been identified that produce and break down endocannabinoids (eCBs) and modulate CB(1) function. Localization of these proteins is critical to defining specific cannabinoid signaling circuitry in the retina. Here we show the localization of diacylglycerol lipase-alpha and -beta (DGLalpha/beta), implicated in the production of the eCB 2-arachidonoyl glycerol (2-AG); monoacylglycerol lipase (MGL) and alpha/beta-hydrolase domain 6 (ABHD6), both implicated in the breakdown of 2-AG; cannabinoid receptor-interacting protein 1a (CRIP1a), a protein that may modulate CB(1) function; and fatty acid amide hydrolase (FAAH) and N-acylethanolamine-hydrolyzing acid amidase (NAAA), which have been shown to break down the eCB anandamide and related acyl amides. Our most prominent finding was that DGLalpha is present in postsynaptic type 1 OFF cone bipolar cells juxtaposed to CB(1)-containing cone photoreceptor terminals. CRIP1a is reliably presynaptic to DGLalpha, consistent with a possible role in cannabinoid signaling, and NAAA is restricted to retinal pigment epithelium, whereas DGLbeta is limited to retinal blood vessels. These results taken together with previous anatomical and functional studies define specific cannabinoid circuitry likely to modulate eCB signaling at the first synapse of the retina as well as in the inner plexiform layer.
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PMID:Architecture of cannabinoid signaling in mouse retina. 2065 38


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