Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neutrophils isolated from the pleural cavity of rats 3 hr after the intrapleural injection of carrageenan metabolize exogenously added arachidonic acid via cyclooxygenase and lipoxygenase. In addition, these cells esterify arachidonic acid to produce diarachidonyl diglyceride. The structure of the diglyceride was determined with the use of various chemical and enzymatic digestions, gas chromatography-mass spectrometry, and 252Cf plasma-desorption mass spectrometry. The formation of this unique diglyceride is stimulated by the presence of nonsteroidal anti-inflammatory drugs. Some of the possible consequences of diarachidonyl diglyceride production are discussed.
Mol Pharmacol 1982 May
PMID:The formation of diarachidonyl diglyceride by rat neutrophils. 681 89

A cDNA clone encoding a lipoxygenase was obtained from a subtracted cDNA library specific for the gametophyte of Porphyra purpurea. The amino acid sequence of the P. purpurea lipoxygenase is most similar to the sequences of animals and plants in the iron-binding, catalytic region located in the C-terminal half of the enzymes. Northern hybridization confirmed that the gene represented by this cDNA is expressed only in the gametophyte.
Mol Mar Biol Biotechnol 1994 Aug
PMID:Isolation of a gametophyte-specific cDNA encoding a lipoxygenase from the red alga Porphyra purpurea. 752 79

Membrane phospholipid degradation has been proposed to play a key role in hypoxic-ischemic brain injury. We tested the hypotheses that both nordihydroguaiaretic acid, a phospholipase A2 and lipoxygenase inhibitor, and RHC 80267, a diacylglycerol lipase inhibitor, would decrease the release of [3H]arachidonic acid metabolites from prelabeled cultures of astroglia subjected to combined glucose-oxygen deprivation and that these inhibitors would also decrease astroglial injury during combined glucose-oxygen deprivation. Both nordihydroguaiaretic acid and RHC 80267 significantly inhibited the release of [3H]arachidonic acid metabolites during combined glucose-oxygen deprivation. This suggests that two separate enzymic pathways, the phospholipase A2 pathway and the phospholipase C/diacylglycerol lipase pathway, contribute to the release of astroglial [3H]arachidonic acid metabolites during combined glucose-oxygen deprivation. However, both of these lipase inhibitors increased astroglial cell death during combined glucose-oxygen deprivation, probably due to inhibition of arachidonic acid release. We speculate that arachidonic acid release may be a mechanism of astroglial self-preservation during combined glucose-oxygen deprivation.
Mol Chem Neuropathol 1995 May
PMID:Nordihydroguaiaretic acid and RHC 80267 potentiate astroglial injury during combined glucose-oxygen deprivation. 754 17

Activation of N-methyl-D-aspartate (NMDA) receptors is required for induction of some lasting changes in nervous system structure and function. The cellular mechanisms involved in transducing receptor stimulation into long-lasting changes in cellular activity are unknown. Immediate-early genes (IEGs) have been implicated in the conversion of short term stimuli to long term changes in cellular phenotype, by regulation of gene expression. Activation of NMDA receptors on dentate gyrus neurons triggers the transcriptional activation of several IEGs. To determine whether the same intracellular pathways transduce the signal from this ligand-gated ion channel to the nucleus, we compared NMDA induction of two IEGs. NMDA was sufficient to produce a striking increase in both c-fos and NGFI-A mRNAs in dentate granule neurons, in a calcium-dependent manner. The induction of both IEGs was blocked by structurally distinct inhibitors of phospholipase A2, an enzyme that catalyzes phospholipid degradation and formation of arachidonic acid. Arachidonic acid itself is catalyzed to biologically active metabolites by multiple enzymes, including cyclooxygenase and lipoxygenase. Selective inhibitors of cyclooxygenase attenuated NMDA induction of c-fos but not NGFI-A. Conversely, structurally distinct inhibitors of lipoxygenase blocked NMDA induction of NGFI-A but not c-fos. The signaling pathways linking NMDA receptors to the transcriptional activation of c-fos and NGFI-A are related but distinct. We suggest that phospholipase A2 and the arachidonic acid cascade play a pivotal role in NMDA receptor regulation of gene expression.
Mol Pharmacol 1995 Jun
PMID:N-methyl-D-aspartate receptors activate transcription of c-fos and NGFI-A by distinct phospholipase A2-requiring intracellular signaling pathways. 760 50

We describe eicosanoid biosynthesis by microsomal-enriched preparations of hemocytes from larvae of the tobacco hornworm Manduca sexta. Four major prostaglandins, PGA2, PGE2, PGD2, and PGF2 alpha, and a lipoxygenase product that co-chromatographed with 15-hydroxyeicosatetraenoic acid (HETE) were synthesized under most conditions. The HETE's fraction was the predominant product. Eicosanoid biosynthesis was sensitive to experimental conditions, including incubation time, temperature, and protein concentration. Optimal biosynthesis was observed with 1.5 mg of microsomal-enriched protein, incubated at 30 degrees C for 2 min. The hemocyte preparation is sensitive to low dosages of naproxin and esculetin. As in mammals, most lipoxygenase activity (87%) was localized in the cytosolic fraction of hemocytes. Unlike mammals, in which PGH synthase is associated with intracellular membranes, the hemocytic activity was detected in microsomal (59%), cytosolic (35%) and mitochondrial fractions (5%).
Insect Biochem Mol Biol 1995 Jun
PMID:Eicosanoid biosynthesis by hemocytes from the tobacco hornworm, Manduca sexta. 762 6

In the present investigation, we evaluated the roles of calcium, calcium-calmodulin, inositol turnover, and protein kinase C in the release of lipoxygenase-derived metabolites with neutrophil chemotactic activity (NCA) from bronchial epithelial cells (BECs) in response to endotoxin (ETX) and opsonized zymosan (OZ). Both ETX and OZ stimulated BECs to release NCA [56.9 +/- 5.1 (ETX), 65.2 +/- 5.1 (OZ) versus 15.2 +/- 3.0 (controls) cells/high power field, P < 0.001]. The lipoxygenase inhibitors, nordihydroguaiaretic acid and diethylcarbamazine, and phospholipase A2 inhibitors, mepacrine and dibucaine, blocked the release of NCA in response to ETX, OZ, calcium ionophore A23187 (A23187), and phorbol myristate acetate (PMA). The calcium channel blockers, nifedipine and verapamil, and two putative inhibitors of calcium release from intracellular storage sites, 8-(N,N-diethylamine)-octyl-3,4,5-trimethoxybenzoate hydrochloride and ruthenium red, inhibited the release of NCA induced by ETX but had little effect on the release of NCA induced by OZ. However, depletion of extracellular calcium inhibited the release of NCA in response to both ETX and OZ. Calmodulin inhibitors, compound 48/80 and N-(6-aminohexyl)-1 naphthalenesulfonamide (W-7), inhibited the release of NCA in response to a variety of endotoxin concentrations. Lithium chloride, an inositol turnover inhibitor, inhibited the release of NCA in response to both ETX and OZ, but less attenuation was observed in the response to OZ. A protein kinase C inhibitor, dihydrosphingosine, inhibited the release of NCA in response to both ETX and OZ. Finally, A23187 and PMA stimulated the release of NCA and [3H]arachidonic acid independently and additively. These data suggest that the release of NCA from BECs in response to OZ may be predominantly mediated by inositol turnover and protein kinase C and that the release of NCA in response to ETX may be regulated by calcium influx and calcium release from intracellular storage sites, calcium-calmodulin activation, inositol turnover, and protein kinase C activation. Protein kinase C augmented the release of NCA and [3H]arachidonic acid independent of and in combination with calcium. These results may suggest the calcium and protein kinase C dependency of the release of NCA from BECs.
Am J Respir Cell Mol Biol 1995 Sep
PMID:Calcium and protein kinase C dependency of lipoxygenase-derived neutrophil chemotactic activity release from bronchial epithelial cells. 765 91

A cDNA clone (loxg) corresponding to a gene repressed during carpel development has been isolated from a cDNA library of unpollinated carpels induced to grow by treatment with gibberellic acid (GA3). The sequences of loxg cDNA and the deduced polypeptide have a high similarity with legume type 2 lipoxygenases, especially with Phaseolus lox1 (78.5% similarity at the protein level) and pea and soybean lox3 (83.6% and 85.4%, respectively). loxg expression is constant in unstimulated carpels but it decreases in carpels induced to keep growing by fertilization or hormone treatment. A similar pattern of repression was observed in lipoxygenase activity of pea and tomato carpels. In situ hybridization studies showed that loxg mRNAs are present in the endocarp and the mesocarp of pea pods; no loxg expression was detectable either in the pod exocarp or in the ovules. Loxg is also expressed in other young growing tissues, especially in flower organs. Nevertheless, the natural pattern of flower and fruit development is associated with loxg repression.
Plant Mol Biol 1995 Mar
PMID:Repression of the pea lipoxygenase gene loxg is associated with carpel development. 776 79

Previous studies have shown that stimulating pituitary GH4C1 cells with thyrotropin-releasing hormone (TRH) evoked a biphasic change in cytosolic free Ca2+ concentration ([Ca2+]i): a rapid release of sequestered Ca2+ due to the production of inositol-1,4,5-trisphosphate, and Ca2+ entry via both voltage-operated Ca2+ channels and a presently unknown voltage-independent influx pathway. The aim of the present study was to further evaluate to which extent the TRH-evoked changes in [Ca2+]i were dependent on entry of extracellular Ca2+, and which mechanisms participated in regulating this Ca2+ entry. Pretreatment of the cells with 4-bromophenylacylbromide (an inhibitor of phospholipase A2), nordihydroguaiaretic acid (an inhibitor of lipoxygenase), and econazole (an inhibitor of both lipoxygenase and cytochrome P-450 enzymes), attenuated the TRH-evoked increase in [Ca2+]i, suggesting that noncyclooxygenase metabolites of arachidonic acid or cytochrome P-450 metabolites may participate in regulating the TRH-evoked entry of extracellular Ca2+. Both nordihydroguaiaretic acid and econazole showed a similar inhibition of the Ca2+ entry, as did SKF 96365, a compound previously shown to inhibit receptor-activated Ca2+ entry. We also showed that arachidonic acid per se increased [Ca2+]i, and acidified the cytosol in GH4C1 cells in a dose-dependent manner. The effects of arachidonic acid was reversed by addition of BSA to the cell suspension. The calcium entry and the activation of the metabolism of arachidonic acid may thus be important components of the TRH-evoked signal-transduction pathway in GH4C1 cells.
Mol Cell Endocrinol 1994 Jun
PMID:TRH-evoked entry of extracellular calcium in GH4C1 cells: possible importance of arachidonic acid metabolites. 792 62

Part of the 5'-flanking sequence of a pea (Pisum sativum) lipoxygenase (LOX) gene was cloned, after amplification from genomic DNA by inverse polymerase chain reaction. Translational and transcriptional fusions of 818 bp of the 5'-flanking region and its deletion derivatives (-513 and -356) were made to a beta-glucuronidase (GUS)-coding sequence and introduced into tobacco. Analysis of T1 transformants showed that the 818 bp 5'-flanking sequence drove GUS expression in seeds that was temporally regulated in a fashion similar to the accumulation of LOX mRNA in developing pea seeds. Contrary to expectations, however, expression of the 818 bp promoter-GUS fusion was not seed-specific; GUS activity was highest in leaves and also present in stems and, to a lesser extent, roots. Deletion analyses identified the region between -818 and -513 as essential for high-level, temporally regulated expression in seeds and also indicated that the sequence between -513 and -356 plays a negative role in leaf/stem, but not seed, expression. Comparison of translational and transcriptional fusions indicated that the LOX initiation codon was used more efficiently than the GUS initiation codon by the tobacco leaf translational apparatus.
Plant Mol Biol 1994 Oct
PMID:Isolation of a pea (Pisum sativum) seed lipoxygenase promoter by inverse polymerase chain reaction and characterization of its expression in transgenic tobacco. 794 73

We investigated the effects of cultured epithelial cells and supernatants on resting membrane potential and excitatory neuroeffector transmission in smooth muscle cells of dog trachea and bronchioles. The mean resting membrane potential of the mucosa-free tracheal smooth muscle cells was -59.5 +/- 1.5 mV (+/- SD). Application of cultured epithelial cells (> 2.5 x 10(5) cells/ml) hyperpolarized the membrane, resulting in a potential of -64.5 +/- 1.7 mV. The supernatant of the cultured epithelial cells also increased the resting membrane potential of the mucosa-free tracheal smooth muscle cells by 4 to 9 mV. These hyperpolarizing actions were not modified by indomethacin (10(-5) M), l-NG-nitroarginine (10(-5) M), or oxyhemoglobin (10(-5) M), but were inhibited by glibenclamide (10(-6) M). The supernatants of the cultured epithelial cells completely or partially suppressed the contractile response of epithelium-denuded bronchioles to electrical field stimulations and suppressed the amplitude of excitatory junction potentials of the trachealis evoked by electrical field stimulations. Indomethacin prevented the inhibitory effect of supernatants on the amplitude of twitch contractions and excitatory junction potentials and markedly suppressed supernatant-associated inhibition of the excitatory neuroeffector transmission. Furthermore, indomethacin with AA861, a lipoxygenase inhibitor, completely suppressed this effect. Our findings suggest that cultured airway epithelial cells spontaneously release at least two factors. One factor selectively modulates the resting membrane potential, and the other inhibits the excitatory neuroeffector transmission.
Am J Respir Cell Mol Biol 1994 Mar
PMID:Effects of epithelial cell supernatant on membrane potential and contraction of dog airway smooth muscles. 811 50


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