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

---

Query: EC:3.1.4.3 (phospholipase C)
18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Na(+)-Ca2+ exchange contributes to regulation of cytosolic free Ca2+ levels ([Ca2+]i) of cultured human mesangial cells following phospholipase C stimulation, as shown by larger responses to vasoconstrictors such as angiotensin II (ANG II) or endothelin 1 in Na(+)-free media. In turn, previous activation of phospholipase C by vasoconstrictors significantly enhances the amplitude of the [Ca2+]i elevation induced by Na+ withdrawal. We studied the mechanisms of upregulation in monolayer cultures loaded with the fluorescent Ca(2+)-sensitive probe fura-2. The exchanger was stimulated by insulin and inhibited by chronic exposure to serum. A rise of [Ca2+]i was not sufficient per se to enhance exchange activity, as prior elevation of [Ca2+]i with the ionophores ionomycin or 8-bromo-A23187 failed to augment the response to Na+ withdrawal. Protein kinase C (PKC) activation by phorbol 12-myristate-13-acetate (PMA), alone or in combination with a rise of [Ca2+]i, potently inhibited basal and vasoconstrictor-enhanced Na(+)-Ca2+ exchange. Suppression of the effects of ANG II was not due to frustrated phospholipase C activation by PMA, because addition of PMA after ANG II also inhibited Na(+)-Ca2+ exchange. PKC downregulation by 24-h pretreatment with PMA or inhibition with 1-(5-isoquinolinesulfonyl)-2-methylpiperazine or staurosporine did not prevent activation by ANG II. The exchanger was markedly potentiated by Na+ loading the cells with gramicidin D or reducing extracellular K+. ANG II failed to stimulate Na(+)-Ca2+ exchange when added in the absence of extracellular Na+. Therefore vasoconstrictors promote Na(+)-Ca2+ exchange by a mechanism independent of [Ca2+]i and PKC while presumably linked to Na+ influx.
...
PMID:Regulation of Na(+)-Ca2+ exchange in cultured human mesangial cells. 171 60

Our recent studies have demonstrated the presence in neonatal islet cells and intact adult islets of a phosphatidylcholine-directed phospholipase D (PLD) which is activated after phorbol ester stimulation. The present study describes PLD activation in the presence of a carbohydrate insulin secretagogue. At the highest concentration tested (20 mM) the triose, glyceraldehyde, induced formation of phosphatidic acid in cells prelabeled with [14C]arachidonic acid or [3H]myristic acid (164 +/- 7 and 210 +/- 9% of basal phosphatidic acid values, respectively). Experimental confirmation of a concentration-dependent specific activation of PLD was provided by the formation of a transphosphatidylation product, phosphatidylethanol, after stimulation with glyceraldehyde in the presence of added ethanol (1.5%). Additionally, there was an early (within 5 min) rise in [14C]arachidonate-labeled diacylglycerol (139 +/- 7% of basal) accompanied by an increase in intracellular diacylglycerol mass (51 +/- 2 pmol/mg protein) and an increase in membrane-associated protein kinase C activity (183 +/- 5% of basal) which preceded the activation of PLD, as indicated by the time course of glyceraldehyde-stimulated phosphatidylethanol formation in the presence of ethanol. Pretreatment of islet cells with 2 microM 12-O-tetradecanoylphorbol-13-acetate for 18 h, to down-regulate protein kinase C, was without effect on diacylglycerol and phosphatidic acid production after 5 min but inhibited completely the production of phosphatidylethanol at 30 min. The phosphohydrolase inhibitor propranolol (100 microM) potentiated the accumulation of phosphatidic acid and phosphatidylethanol incubation following incubation with glyceraldehyde. These findings demonstrate for the first time that a physiological nutrient activates a phospholipase directed against endogenous phosphatidylcholine in intact islet cells; furthermore, they indicate a role for PLD in a delayed formation of phosphatidic acid in the islet cell. The finding of an early rise in glyceraldehyde-stimulated diacylglycerol (which may be formed de novo or by the action of phospholipase C), suggests that PLD is recruited by the activation of protein kinase C by this nutrient.
...
PMID:Activation of phospholipase D by glyceraldehyde in isolated islet cells follows protein kinase C activation. 172 27

1. Incubation of C6 glioma cultures with insulin resulted in a time and dose-dependent stimulation of 2-deoxy-D-glucose uptake. The maximal stimulation (160% of the control) was observed with 1 nM insulin and 0.05 nM caused half-maximum effect. 2. Incubation of NG 108-15 (neuroblastoma x glioma hybrid) and N2 neuroblastoma cells with 160 nM insulin did not result in a significant stimulation of this glucose uptake. 3. The basal level and stimulatory effect by insulin on this glucose uptake observed in C6 glioma cells were dependent on the presence of calcium in the medium. 4. Such an increase in glucose uptake in C6 glioma cells was also observed in the presence of diacylglycerol (DG) generating agents, such as carbachol (1 mM) and phospholipase C (0.05 unit/ml) or of DG analogs, such as sn-1,2-dioctanoyl glycerol (250 microM) and phorbol myristate acetate (1 microM). 5. Our results indicated that both calcium ion and DG levels play important roles in the regulation of glucose uptake in the glial cells, but not in neuronal cells from the brain.
...
PMID:Effects of insulin on glucose uptake in cultured cells from the central nervous system of rodent. 177 90

Human decidual tissue synthesizes and secretes a protein that is identical to pituitary prolactin in its chemical, biological and immunological properties. Nevertheless, the factors that regulate the synthesis and release of prolactin from the decidual tissues appear to be different to those regulating the synthesis and release of pituitary prolactin. Studies from our laboratory over the past few years indicate that the synthesis and release of decidual prolactin are regulated, at least in part, by factors released by placenta, fetal membranes and decidua. The placenta releases a 23.5 KMr protein [decidual prolactin-releasing factor (PRL-RF)] that stimulates a rapid release of prolactin within the first few minutes of exposure and a sustained, prolonged, increase in the synthesis and release of prolactin beginning 6-8 h after exposure. The acute release of prolactin in response to PRL-RF is inhibited by decidual prolactin release-inhibitory factor (PRL-IF), a 35-45 K Mr protein that is released by the decidua. The secondary increase in the synthesis and release of prolactin in response to PRF-RF is blocked by lipocortin I, which is synthesized by both the placenta and decidua. IGF-I, insulin and relaxin also stimulate the synthesis and release of prolactin. However, the stimulation in response to these factors does not occur until 24-48 h after exposure. The cellular mechanisms involved in the release of decidual prolactin are as yet unknown. However, recent studies implicate activation of adenylate cyclase, phospholipase C-mediated phosphoinositide hydrolysis and phospholipase A2-mediated arachidonic acid release in the regulation of prolactin release. The finding that the synthesis and release of decidual prolactin are regulated, at least in part, by PRL-RF, IGF-I, insulin, relaxin and lipocortin I strongly suggests that there is novel feedback regulation between the placenta, fetal membranes, and decidua in the regulation of the synthesis and release of decidual prolactin.
...
PMID:Regulation of the synthesis and release of decidual prolactin by placental and autocrine/paracrine factors. 183 Dec 61

Glycerol-3-phosphate acyltransferase (G3PAT) was activated by insulin in intact rat adipocytes within 1 min: this activation persisted for 10 min, and was due to a decrease in the Km of the enzyme. The addition of insulin to control adipocyte membranes also increased G3PAT activity, and this effect was mimicked by phosphatidylinositol-specific phospholipase C. Cytosol fractions from insulin-treated adipocytes stimulated G3PAT activity of control membranes, suggesting that a soluble mediator is released during insulin action, possibly through activation of a PI-specific PLC.
...
PMID:Insulin rapidly increases glycerol-3-phosphate-acyltransferase activity in rat adipocytes. 184 21

Skin fibroblasts from newborn spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were cultured to study their growth rate and their reactivity to various agonists in terms of mitogenic potency and inositol phosphate production. A marked enhancement of nuclear 3H-thymidine incorporation, occurring after stimulation of quiescent fibroblasts by fetal calf serum, correlated with the increased growth rate of these cells with regard to WKY ones. Insulin (1 microgram/ml) and epidermal growth factor (10 ng/ml) induced two and four times greater DNA synthesis in SHR fibroblasts compared to WKY cells, without activating the phospholipase C pathway. In contrast, angiotensin II, bradykinin, vasopressin which stimulated inositol phosphate production, and phorbol-12 myristate 13-acetate were unable to stimulate DNA synthesis. Higher levels of tritiated inositol phosphates were produced in SHR cells after serum, bradykinin and angiotensin II stimulation, but not in WKY cells after vasopressin. This enhanced mitogenic response of SHR skin fibroblasts is probably due to a genomic alteration and appears to be independent of the hyperactivation of the phospholipase C to some vasoactive agonists.
...
PMID:Enhanced response to growth factors and to angiotensin II of spontaneously hypertensive rat skin fibroblasts in culture. 184 54

Incubation of isolated cardiac myocytes from rat hearts with heparin or phosphatidylinositol-specific phospholipase C (PLC) resulted in the release of lipoprotein lipase (LPL) into the medium. The release of LPL by the combination of heparin and PLC was not additive, and preincubation of cardiac myocytes with heparin eliminated the release of LPL in a subsequent incubation with PLC. This evidence suggests that LPL may be bound ionically to heparan sulfate proteoglycans that are covalently linked to the cell surface of cardiac myocytes by a phosphatidylinositol-glycan membrane anchor; a second pool of LPL may also be bound to proteoglycans attached directly to the myocardial cell surface. The induction of diabetes by the administration of streptozotocin (100 mg/kg for 3-4 days) to rats resulted in a decrease in the initial cellular activity of LPL and a marked reduction in the heparin-induced secretion of LPL into the medium of cardiac myocytes. The intravenous administration of insulin (5 U for 1 h) in diabetic rats reversed the effects of diabetes on cellular and heparin-releasable LPL activities. Diabetes also reduced the PLC-induced release of LPL. The reduction in the release of LPL from diabetic cardiac myocytes could result in a decrease in functional LPL activity at the capillary endothelium of whole hearts.
...
PMID:Diabetes reduces heparin- and phospholipase C-releasable lipoprotein lipase from cardiomyocytes. 184 7

Despite significant advances in the past few years on the chemistry and biology of insulin and its receptor, the molecular events that couple the insulin-receptor interaction to the regulation of cellular metabolism remain uncertain. Progress in this area has been complicated by the pleiotropic nature of insulin's actions. These most likely involve a complex network of pathways resulting in the coordination of mechanistically distinct cellular effects. Since the well-recognized mechanisms of signal transduction (i.e., cyclic nucleotides, ion channels) appear not to be central to insulin action, investigators have searched for a novel second messenger system. A low-molecular-weight substance has been identified that mimics certain actions of insulin on metabolic enzymes. This substance has an inositol glycan structure, and is produced by the insulin-sensitive hydrolysis of a glycosyl-phosphatidylinositol in the plasma membrane. This hydrolysis reaction, which is catalyzed by a specific phospholipase C, also results in the production of a structurally distinct diacylglycerol that may selectively regulate one or more of the protein kinases C. The glycosyl-phosphatidylinositol precursor for the inositol glycan enzyme modulator is structurally analogous to the recently described glycosyl-phosphatidylinositol membrane protein anchor. Preliminary studies suggest that a subset of proteins anchored in this fashion might be released from cells by a similar insulin-sensitive, phospholipase-catalyzed reaction. Future efforts will focus on the precise role of the metabolism of glycosyl-phosphatidylinositols in insulin action.
...
PMID:The role of glycosyl-phosphoinositides in hormone action. 184 35

Insulin modifies the effects of PTH on osteoblast-like cells. However, the basis for this effect is unknown. In bone and kidney cells, the effects of PTH on cellular function are mediated by second messengers generated through both the phospholipase C and adenylate cyclase systems. Therefore, we examined the effects of insulin on PTH second messenger generation in UMR-106-01 rat osteoblastic osteosarcoma cells. PTH produced a rapid, transient increase in intracellular free calcium concentration ([Ca2+]i) which was maximal at 30 sec and was only minimally reduced in the absence of extracellular calcium. Inositol-triphosphate (IP3) production was increased in parallel. PTH stimulation of [Ca2+]i was concentration-dependent from 0.5-1,000 nM, with half-maximal stimulation at approximately 50 nM PTH. A 30-sec exposure to 50 nM PTH produced 32% and 23% increases in IP1 and IP3 production, respectively (both P less than 0.05). Although insulin alone did not significantly alter basal [Ca2+]i, a 1-min exposure to 1-100 nM insulin produced a concentration-dependent suppression of the PTH-stimulated transient increase in [Ca2+]i and IP3 generation. 100 nM insulin decreased 50 nM PTH stimulation of [Ca2+]i and IP3 levels by 84% (P less than 0.02) and 80% (P less than 0.001), respectively. Preexposure to insulin also decreased PTH stimulation of intracellular cAMP levels, but to a lesser degree. A 1-min exposure to 100 nM insulin produced a 32% (P less than 0.01) decrease in PTH-stimulated cAMP generation, but lower insulin concentrations were without significant effects. These results demonstrate that in UMR-106-01 cells, insulin suppresses PTH stimulation of second messengers generated through both the phospholipase C and adenylate cyclase systems, but has a more marked effect on the former.
...
PMID:Insulin acutely suppresses parathyroid hormone second messenger generation in UMR-106-01 osteoblast-like cells: differential effects on phospholipase C and adenylate cyclase activation. 185 51

Glycosylated phosphatidylinositol (gly-Pl) molecules have been implicated as precursors for insulin-sensitive second messengers (1-4) and lipid-anchored membrane proteins (5-9). The relationship between the diverse functions of these lipids and their predicted structural heterogeneity within gly-Pl subtypes was examined in human T lymphocytes. Four subtypes of gly-Pl molecules were identified in T lymphocytes after separation over high-performance thin-layer chromatography by sensitivity to Pl-specific phospholipase C and nitrous acid. Antibody probes of the glycan domain of gly-Pl were developed and used to assess the partial sensitivity of gly-Pl to insulin action. This analysis showed that the effects of insulin are linked to differential utilization of only two of the four gly-Pl subtypes in T lymphocytes. Polar fragments of this reaction were identified in extracellular supernatants from insulin-treated cells. The biological significance of insulin-dependent gly-Pl hydrolysis was demonstrated by insulin and inositol phosphoglycan regulation of glucose metabolism in intact lymphocytes. These results support the hypothesis that multifunctional roles of gly-Pl are served by discrete gly-Pl populations and that metabolites of gly-Pl subsets participate as signaling elements in insulin action.
...
PMID:Differential regulation of glycosylated phosphatidylinositol subtypes by insulin. 193 92


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---