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Query: UNIPROT:P06889 (Mol)
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An ability to destroy carotenoids in the rumen of cattle may be an effective method of limiting their absorption from the small intestine which, in turn, is likely to result in reduced adipose tissue colour. Plant lipoxygenases are well known for their ability to bleach beta-carotene. As lutein is the major carotenoid present in most forage grasses, we have investigated the bleaching of lutein as well as beta-carotene by lipoxygenase isolated from soybeans. In vitro studies, using micellar preparations of carotenoids, indicated that lutein was rapidly oxidised and that the progress of the reaction was similar to that observed for beta-carotene. The polyunsaturated fatty acid linoleate was essential. When bovine rumen fluid was used as a source of carotenoid for in vitro studies with preparations of lipoxygenase, a rapid decrease in carotenoid and chlorophyll concentrations was observed, again requiring the addition of linoleic acid. The direct addition of soya flour to bovine rumen fluid resulted in the effective bleaching of the pigments without the inclusion of linoleate. When compared with flours from a variety of other plant sources, soya flour was most effective. The inclusion of dietary sources of lipoxygenase may be an effective method for controlling carotenoid uptake in certain ruminant species.
Biochem Mol Biol Int 1993 Jun
PMID:The in vitro destruction of rumen fluid carotenoids by plant lipoxygenases. 836 3

Arachidonic acid (AA) stimulated protein phosphorylation in electrically permeabilised islets, most notably of an islet protein of approximate molecular weight 18 kDa. This protein did not appear to be a substrate for cAMP-dependent protein kinase. The AA-induced protein phosphorylation was mediated by unmetabolised AA since the lipoxygenase inhibitor, nordihydroguaretic acid (NDGA), or the cyclooxygenase inhibitor, indomethacin, did not significantly reduce AA-induced phosphorylation. Although saturated fatty acids did not stimulate phosphorylation of islet proteins, a number of cis-unsaturated fatty acids, other than AA, induced 32P incorporation into an 18 kDa protein. However, some fatty acids which stimulated protein phosphorylation had no effect on insulin secretion in experiments where AA clearly stimulated insulin secretion. AA stimulated protein kinase C (PKC) activity extracted from islets but several fatty acids which induced protein phosphorylation had no significant effect on PKC activity in vitro. 50 nM staurosporine had no effect on AA-induced protein phosphorylation but this concentration of staurosporine markedly inhibited PKC activity. 200 nM staurosporine caused complete inhibition of the AA-induced phosphorylation without having any effect on AA-induced insulin secretion. These results suggest that AA and some other fatty acids can promote 32P incorporation into islet proteins, independently of PKC activation, and that AA-induced phosphorylation is not required for insulin secretory responses to AA.
Mol Cell Endocrinol 1993 Feb
PMID:Arachidonic acid-induced insulin secretion from rat islets of Langerhans is not mediated by protein phosphorylation. 838 12

The relationship between the phospholipase-stimulating and immunosuppressive properties of cyclosporin A (CsA) has been investigated in vitro. At concentrations of 0.025 microM and upwards, CsA caused dose-related inhibition of both mitogen- and alloantigen-stimulated uptake of tritiated thymidine by human mononuclear leukocytes (MNL), which was associated with a time- and dose-related enhancement of the generation of lysophosphatidylcholine (LPC), arachidonic acid, and prostaglandin E2 from mitogen-stimulated cells. Arachidonate alone, at concentrations of up to 20 microM, did not affect lymphocyte activation, whereas cyclooxygenase and 5'-lipoxygenase inhibitors failed to protect the cells against the antiproliferative effects of CsA. However, LPC caused dose-related inhibition of MNL proliferation. Moreover, coincubation of MNL with alpha-tocopherol, a lysophospholipid-complexing agent, or with lysophospholipase protected the cells against CsA, as well as against LPC. The Na+,K(+)-ATPase activity of mitogen-activated lymphocytes was also inhibited by CsA, whereas inclusion of alpha-tocopherol or lysophospholipase protected this enzyme. Excessive production of lysophospholipids and consequent inhibition of Na+,K(+)-ATPase during CsA treatment of mitogen- or antigen-activated lymphocytes is a possible biochemical mechanism of the immunosuppressive activity of this agent.
Mol Pharmacol 1993 Sep
PMID:Lysophospholipid-mediated inhibition of Na+,K(+)-adenosine triphosphatase is a possible mechanism of immunosuppressive activity of cyclosporin A. 839 20

More than 600 potentially nodule-specific clones have been detected by differential hybridization of a broadbean cDNA library constructed from root nodule poly(A)+ RNA. These isolated cDNAs belong to at least 28 different clone groups containing cross-hybridizing sequences. The number of clones within a clone group varies from about 200 to only one single clone. Northern hybridization experiments revealed nodule-specific transcripts for 14 clone groups and markedly nodule-enhanced transcripts for another 7 clone groups. Sequence homologies indicate that three transcript sequences code for different leghemoglobins. Two other transcripts encode a nodule-specific sucrose synthase and a nodule-enhanced asparagine synthetase, respectively. Four deduced gene products are proline-rich, two of them being the homologues of PsENOD2 and PsENOD12. The third proline-rich protein (PRP) is composed of similar amino acid repeats as the nodule-specific PsENOD12 but is expressed in nodules and roots in comparable amounts. The fourth PRP is a nodule-enhanced extensin-type protein built up by Ser-Pro4 repeats. Two further nodule-specific transcripts encode gene products showing some similarity to structural glycine-rich proteins. Additionally, transcripts could be identified for broadbean homologues of the nodulins MsNOD25, PsENOD3 and PsENOD5 and transcripts specifying a nodule-enhanced lipoxygenase and a translation elongation factor EF-1 alpha, which is expressed in all broadbean tissues tested.
Plant Mol Biol 1993 Sep
PMID:A survey of transcripts expressed specifically in root nodules of broadbean (Vicia faba L.). 840 Jan 40

Primary leaves of 7- to 9-day-old Red Mexican bean plants were inoculated with virulent or avirulent isolates of Pseudomonas syringae pv. phaseolicola, or saprophytic P. fluorescens either by vacuum infiltration of the whole leaf lamina, or by syringe-inoculation of selected leaf panels. In the incompatible combination, resistance was associated with a hypersensitive response (HR). Syringe-inoculated leaves were sampled in three zones: zone 1, the inoculated leaf area; zone 2, the surrounding 0.5-0.7 cm of leaf tissue; and zone 3, the remainder of the leaf. Northern blots of RNA from zones 1, 2, and 3 were probed with bean cDNAs for phenylalanine ammonia-lyase (PAL), chalcone synthase (CHS), chitinase (CHT), and lipoxygenase (LOX). Accumulation of PAL, CHS, and CHT transcripts was more rapid and generally of greater magnitude in the incompatible than in the compatible interaction and, in both cases, was observed essentially only in zone 1 tissues. Similarly, antibacterial phytoalexins were only detected in zone 1 from the incompatible interaction. Young primary leaves have a background level of LOX transcripts, which declines as leaves age. This decline was accelerated over the first 12 hr postinoculation (hpi) with avirulent bacteria, whereas a weak transient induction, peaking at 5-6 hpi, was observed in the compatible interaction. A subsequent, strong accumulation of LOX transcripts was seen in both the compatible and incompatible interactions outside the inoculation site starting about 14 hpi. LOX transcripts did not accumulate at the inoculation site itself in the incompatible interaction compared to a relatively strong induction in the compatible interaction. Interestingly, inoculation of leaves with cells of the saprophyte P. fluorescens also induced the accumulation of transcripts for CHS, CHT, and LOX, but generally to a lesser degree than in the incompatible interaction. No HR occurred and no macroscopic cell damage was apparent in leaves inoculated with P. fluorescens. However, at the microscopic level individual, trypan blue-stained, necrotic plant cells were visible. In spite of this and the accumulation of CHS transcripts, no phytoalexin accumulation was found up to 48 hr after inoculation. The spatial and temporal relationship of the hypersensitive reaction to defense gene transcript and phytoalexin accumulation is discussed.
Mol Plant Microbe Interact
PMID:Spatial and temporal accumulation of defense gene transcripts in bean (Phaseolus vulgaris) leaves in relation to bacteria-induced hypersensitive cell death. 840 Mar 75

15-hydroxyeicosatetraenoic acid (15-HETE) is the major lipoxygenase metabolite of arachidonic acid produced by human airway epithelial cells. Because HETEs have been shown to be rapidly metabolized and/or incorporated into cellular lipids in other cell types, we investigated the uptake, metabolism, and intracellular distribution of exogenous 15-HETE by primary monolayer cultures of human tracheal epithelial (HTE) cells. At concentrations of 0.1 microM, [3H]15-HETE was rapidly incorporated by HTE cells and also metabolized primarily by beta-oxidation to several more polar products that were released extracellularly. The majority of cell-associated [3H]15-HETE radiolabel was distributed into phospholipids, with phosphatidylinositol (PI) accounting for approximately 75% of phospholipid radiolabel. Exogenous 5- and 12-HETE were also metabolized by HTE cells but were less extensively incorporated into phospholipids and were distributed primarily into phosphatidylcholine and phosphatidylethanolamine. Phospholipase A2 hydrolysis indicated selective esterification of unmodified 15-HETE to the sn-2 position of phospholipids. 15-HETE incorporation into total phospholipids and into PI was saturable (half maximal incorporation at 0.82 and 0.68 microM, respectively), while incorporation into neutral lipids continued to increase at concentrations of 15-HETE up to 5 microM. The incorporation of 15-HETE into PI was metabolically stable, with an intracellular half-life of 12 h, and was not subject to mobilization in response to 5 microM calcium ionophore A23187. HTE cells can incorporate and metabolize HETEs that the cells themselves produce as well as those that might be released by inflammatory cells recruited into the airway.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1993 Mar
PMID:Human tracheal epithelial cells selectively incorporate 15-hydroxyeicosatetraenoic acid into phosphatidylinositol. 844 17

Release of arachidonic acid (AA) and subsequent formation of a lipoxygenase (LOX) metabolite(s) is an obligatory signal to induce spreading of HeLa cells on a gelatin substratum (Chun and Jacobson, 1992). This study characterizes signaling pathways that follow the LOX metabolite(s) formation. Levels of diacylglycerol (DG) increase upon attachment and before cell spreading on a gelatin substratum. DG production and cell spreading are insignificant when phospholipase A2 (PLA2) or LOX is blocked. In contrast, when cells in suspension where PLA2 activity is not stimulated are treated with exogenous AA, DG production is turned on, and inhibition of LOX turns it off. This indicates that the formation of a LOX metabolite(s) from AA released during cell attachment induces the production of DG. Consistent with the DG production is the activation of protein kinase C (PKC) which, as with AA and DG, occurs upon attachment and before cell spreading. Inhibition of AA release and subsequent DG production blocks both PKC activation and cell spreading. Cell spreading is also blocked by the inhibition of PKC with calphostin C or sphingosine. The inhibition of cell spreading induced by blocking AA release is reversed by the direct activation of PKC with phorbol ester. However, the inhibition of cell spreading induced by PKC inhibition is not reversed by exogenously applied AA. In addition, inhibition of PKC does not block AA release and DG production. The data indicate that there is a sequence of events triggered by HeLa cell attachment to a gelatin substratum that leads to the initiation of cell spreading: AA release, a LOX metabolite(s) formation, DG production, and PKC activation. The data also provide evidence indicating that HeLa cell spreading is a cyclic feedback amplification process centered on the production of AA, which is the first messenger produced in the sequence of messengers initiating cell spreading. Both DG and PKC activity that are increased during HeLa cell attachment to a gelatin substratum appear to be involved. DG not only activates PKC, which is essential for cell spreading, but is also hydrolyzed to AA. PKC, which is initially activated as consequence of AA production, also increases more AA production by activating PLA2.
Mol Biol Cell 1993 Mar
PMID:Requirement for diacylglycerol and protein kinase C in HeLa cell-substratum adhesion and their feedback amplification of arachidonic acid production for optimum cell spreading. 848 18

The effect of zinc on the repair of wounded monolayers of bovine aortic endothelial cells in a culture system was investigated. It was morphologically found that zinc promotes the appearance of the cells in the wounded area; cell number in the area was significantly increased by zinc. However, other heavy metals including copper, manganese, nickel and cobalt failed to exhibit a similar effect. The repair induced by exogenous basic fibroblast growth factor (bFGF) was potentiated by zinc but that by exogenous acidic fibroblast growth factor was unaffected by the metal. Promotion of the repair of the wounded area by zinc was completely blocked by either cycloheximide or anti-bFGF antibody. In addition, zinc-induced repair was significantly inhibited by a lipoxygenase inhibitor, nordihydroguaiaretic acid but not by a cyclooxygenase inhibitor, indomethacin. From these results, it is suggested that zinc promotes the repair process of damaged vascular endothelium through the lipoxygenase pathway that mediates the response of vascular endothelial cells to endogenous bFGF.
Res Commun Mol Pathol Pharmacol 1995 Aug
PMID:Zinc promotes the repair of wounded monolayers of cultured vascular endothelial cells. 855 73

Schistosoma mansoni has previously been reported to synthesize a wide range of eicosanoids including prostaglandins, leukotrienes and hydroxyeicosatetraenoic acids (HETEs). Our analysis of arachidonic acid metabolites synthesized by microsomal and cytosolic extracts from adult S. mansoni using thin-layer chromatography and radioimmunoassay techniques indicate the presence of a soluble, enzymatically active lipoxygenase (Lox) and the absence of any cyclooxygenase (Cox) activity. The S. mansoni Lox activity catalyzed the formation of a 15-hydroxyeicosatetraenoic acid (15-HETE)-like species. This activity was calcium-independent and inhibitable by inhibitors of mammalian and plant Lox. The conversion of linoleic acid to a 13-hydroxyoctadecadienoic acid (13-HODE)-like product by S. mansoni extracts indicates that the parasite Lox-homologue is similar to mammalian 15-Lox. Immunoblot analysis of S. mansoni extracts using antisera to different mammalian lipoxygenases detects two immunoreactive proteins with molecular weights similar to plant and mammalian lipoxygenases. In addition, polymerase chain reaction (PCR) amplification of Lox-like sequences from S. mansoni genomic DNA using degenerate primers based on conserved plant and mammalian Lox sequences, generated two PCR products which hybridized to a human 15-Lox cDNA probe. While the role of eicosanoid production in the physiology of S. mansoni is not known, eicosanoids may be essential for normal physiological processes as is the case in other invertebrates. Interestingly, 15-HETE has previously been shown to have immunosuppressive effects in mammals, and this may be related to the ability of the parasite to overcome host immune responses.
Mol Biochem Parasitol 1995 Jul
PMID:Characterization of arachidonic-acid-metabolizing enzymes in adult Schistisoma mansoni. 857 45

Metabolism of arachidonic and linoleic acid can be regulated by polypeptide growth factors in a variety of cell types. In Syrian hamster embryo (SHE) fibroblasts, epidermal growth factor (EGF) stimulates the conversion of exogenous linoleic acid to 13(S)-hydroxyoctadecadienoic acid (HODE). Inhibition of 13-HODE biosynthesis blocks the EGF-mitogenic response in SHE cells, and 13-HODE and its hydroperoxy precursor are potent and highly specific enhancers of EGF-dependent DNA synthesis. We demonstrated that EGF stimulates a biphasic production and release of endogenous 13-HODE. Through development of a stable isotope-dilution GC/MS assay for 13-HODE, we observed 13-HODE production as early as 5 min after EGF stimulation, and this initial phase peaked at 1 hr. A second rise in 13-HODE formation was seen at 2-4 hr, and this phase plateaued at 4-6 hr at a level of 30-40 ng/10(6) cells. EGF stimulation of 13-HODE biosynthesis is not mediated by transcriptional or translational regulation of the inducible form of prostaglandin H synthase. Based on enzyme inhibitor studies and structural characterization of products, the linoleate metabolite is apparently formed by an n-6 lipoxygenase that remains to be characterized. EGF stimulation of 13-HODE formation is linked with activation of the EGF receptor tyrosine kinase. Inhibition of EGF receptor tyrosine kinase activity with methyl-2,5-dihydroxycinnamate blocked EGF-dependent linoleic acid metabolism and EGF-regulated DNA synthesis. Potentiation of the EGF receptor tyrosine phosphorylation cascade through treatment of SHE cells with the tyrosine phosphatase inhibitor vanadate resulted in a 3-fold increase in EGF-stimulated 13-HODE production and a corresponding enhancement of the EGF mitogenic response. The coupling of EGF-regulated linoleic acid metabolism with the EGF receptor tyrosine kinase activity suggests the importance of specific linoleate compounds in mediating mitogenic signal transduction.
Mol Pharmacol 1996 Jun
PMID:Regulation of 13(S)-hydroxyoctadecadienoic acid biosynthesis in Syrian hamster embryo fibroblasts by the epidermal growth factor receptor tyrosine kinase. 864 42


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