Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Formation of inositol polyphosphates has been characterized in cultured bovine adrenal chromaffin cells in terms of calcium dependency and isomers of inositol polyphosphates. There are two distinct pathways of generation of InsP3. Stimulants such as high K+ induce InsP3 accumulation by a calcium uptake-dependent mechanism. Stimulants such as Ang II induce InsP3 accumulation by a calcium uptake-independent mechanism. Both mechanisms are involved in nicotinic stimulation. These results suggest that calcium entry as well as receptor-mediated mechanisms play a significant role in phosphoinositides hydrolysis through phospholipase C in adrenal chromaffin cells. Nicotinic receptor stimulation induces a rapid and transient increase in Ins(1,4,5)P3 accumulation followed by a slower accumulation of Ins(1,3,4)P3. Moreover, nicotine induces a large and rapid increase in Ins(1,3,4,5,6)P5 accumulation with an extent and time course similar to Ins(1,4,5)P3, which peaks at 15 sec after stimulation. Nicotine also induced Ins(1,3,4,5)P4 and InsP6 accumulation with a slower time course and a lesser magnitude than Ins(1,3,4,5,6)P5. These results indicate that adrenal chromaffin cells possess fine regulation of inositol polyphosphates metabolism and that inositol polyphosphates are involved with the control of cellular function in these cells.
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PMID:Formation of inositol polyphosphates in cultured adrenal chromaffin cells. 175 3

Classical nicotinic receptors are neurotransmitter-gated channels that, upon activation by acetylcholine, induce the opening of an intrinsic cationic channel. We have recently observed that, in frog pituitary melanotrophs, nicotine stimulates alpha-melanocyte-stimulating hormone (alpha-MSH) release through a noncholinergic mechanism. In the study reported here, we investigated the intracellular events that mediate the response of frog melanotrophs to nicotine. Nicotine was capable of stimulating alpha-MSH release in the absence of Ca2+ and/or Na+ in the extracellular medium. A short pulse of nicotine induced a rapid and transient increase of cytosolic free Ca2+ concentration ([Ca2+]i). The effect of nicotine on Ca2+ mobilization was not affected in the absence of Na+ and Ca2+ in the extracellular medium, indicating that the nicotine-evoked increase in [Ca2+]i did not result from Na+ or Ca2+ influx. Nicotine induced both an increase in inositol trisphosphate and a reduction in phosphaditylinositol bisphosphate concentrations but did not affect cAMP production. The present results indicate that nicotine-induced stimulation of alpha-MSH release in frog melanotrophs can be explained by activation of inositolphospholipid breakdown and mobilization of inositol triphosphate-dependent intracellular Ca2+ pools. These data provide evidence for the existence of an unusual type of noncholinergic nicotine receptor positively coupled to phospholipase C.
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PMID:Functional characterization of a nonclassical nicotine receptor associated with inositolphospholipid breakdown and mobilization of intracellular calcium pools. 1657 48

It has been established that amyloid beta peptide (AbetaP) activates phospholipase A2, phospholipase C and phospholipase D of LA-N-2 cells and other cell types. Nicotine in addition to being a cholinergic agonist, may be neuroprotective. We have investigated the ability of (-)nicotine to blunt the phospholipase activations by AbetaP in LA-N-2 cells. (-)Nicotine inhibits the AbetaP activation of phospholipase A2, with an IC50 of 76 microM and of phospholipase D with an IC50 of 252 microM. (-)Nicotine did not blunt the AbetaP activation of phospholipase C. These inhibitions of AbetaP activations were not observed with (+)nicotine or cotinine. The (-)nicotine inhibition of AbetaP activation of these two phospholipases was unaffected by hexamethonium and D-tubocurarine. There was no inhibition of the phospholipase A2 activity present in homogenates of LA-N-2 cells. Exposure of LA-N-2 cells to (-)nicotine for 2 h resulted in the blockade of phospholipase A2 activation by kainate and AbetaP but did not affect the ability of quisqualate and AbetaP to activate phospholipase D. These data suggest that if the nicotine inhibition of AbetaP activations is receptor occupancy mediated then it is by an atypical receptor type.
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PMID:(-)Nicotine inhibits the activations of phospholipases A2 and D by amyloid beta peptide. 968 79

Nicotine is not only a major component in tobacco but is also a survival agonist that inhibits apoptosis induced by diverse stimuli including chemotherapeutic drugs. However, the intracellular mechanism(s) involved in nicotine suppression of apoptosis is unclear. Bcl2 is a potent antiapoptotic protein and tumor promotor that is expressed in both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) cells. It is possible that nicotine may regulate Bcl2 to stimulate cell survival. Here we report that nicotine can induce Bcl2 phosphorylation exclusively at the serine 70 site in association with prolonged survival of SCLC H82 cells expressing wild-type but not the phosphorylation-deficient S70A mutant Bcl2 after treatment with chemotherapeutic agents (i.e. cisplatin or VP-16). Nicotine induces activation of PKC alpha and the MAPKs ERK1 and ERK2, which are physiological Bcl2 kinases. Furthermore, ET-18-OCH3, a specific phospholipase C (PLC) inhibitor, blocks nicotine-stimulated Bcl2 phosphorylation and promotes apoptosis, suggesting that PLC may be involved in nicotine activation of Bcl2 kinases. Using a genetic approach, the gain-of-function S70E mutant, which mimics Ser(70) site phosphorylation in the flexible loop domain, potently enhances chemoresistance in SCLC cells. Thus, nicotine-induced cell survival results, at least in part, from a mechanism that involves Bcl2 phosphorylation. Therefore, novel therapeutic strategies for lung cancer in which Bcl2 is expressed may be used to abrogate the anti-apoptotic activity of Bcl2 by inhibiting multiple upstream nicotine-activated pathways.
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PMID:A functional role for nicotine in Bcl2 phosphorylation and suppression of apoptosis. 1242 19

"Pod-based" e-cigarettes such as JUUL are currently the most prevalent electronic nicotine delivery systems (ENDS) in the United States. JUUL-type ENDS utilize nicotine salts protonated with benzoic acid rather than freebase nicotine. However, limited information is available on the cellular effects of these products. Cytoplasmic Ca2+ is a universal second messenger that controls many cellular functions including cell growth and cell death. Of note, dysregulation of cell Ca2+ homeostasis has been linked with several disease processes including autoimmune disease and several types of cancer. We exposed HEK293T cells and THP-1 macrophage-like cells to different JUUL e-liquids. We evaluated their effects on cellular viability and Ca2+ signaling by measuring fluorescence from calcein-AM/propidium iodide and Fluo-4, respectively. E-liquid autofluorescence was used to look for e-liquid permeation into cells. To identify the mechanisms behind the Ca2+ responses, different inhibitors of Ca2+ channels and phospholipase C signaling were used. JUUL e-liquids caused significant cytotoxic effects, with "Mint" flavor being the most cytotoxic. The Mint flavored e-liquid also caused a significant elevation in cytoplasmic Ca2+ . Using autofluorescence, the permeation of JUUL e-liquids into live cells was confirmed, indicating that intracellular organelles are directly exposed to e-liquids. Further studies identified the endoplasmic reticulum as being the source of e-liquid-induced changes in cytoplasmic Ca2+ . Nicotine salt-based e-liquids cause cytotoxicity and elevate cytoplasmic Ca2+ , indicating that they can exert biological effects beyond what would be expected with nicotine alone. These effects are flavor-dependent, and we propose that flavored e-liquids be reassessed for potential lung toxicity.
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PMID:Cellular effects of nicotine salt-containing e-liquids. 3303 66