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:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

12-hydroxy 5,8,14-cis 10-trans eicosatetraenoic acid (12-HETE) and its derivatives are the principal lipoxygenase (Lox) products of the mammalian brain. These metabolites have been proposed to play a key role as second messengers in synaptic transmission and might function as retrograde messengers in learning and memory processes: the long-term potentiation. The exact source(s) of 12-HETE and neuronal implication have not been definitively established. The present work was therefore designed to study 12-Lox mRNA expression in neural cell cultures. Detection of this mRNA from cellular extract was obtained by reverse transcriptase-polymerase chain reaction (RT-PCR) and localization in neurons by in situ RT-PCR. These results argue for 12-Lox neuronal production.
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PMID:12-lipoxygenase mRNA expression by cultured neurons. 753 42

Inflammation has been considered to be related to carcinogenesis. Previously, we demonstrated that 1-hydroxyanthraquinone (1-HA), a naturally occurring carcinogen, induced severe inflammation such as ulcerative colitis in colonic mucosa. We also showed that indomethacin inhibited the tumorigenicity of 1-HA. In this study, we examined the expressions of major enzymes in arachidonic acid cascade related to inflammation in the colon mucosa of rats treated with 1-HA. After the treatment of 1% 1-HA diet, colon lesions were observed and RNA was extracted from mucosa and neoplasms. The mRNA expressions of group II phospholipase A2, cyclooxygenase-2 and 5-lipoxygenase, were examined by using a reverse transcriptase polymerase chain reaction. The expressions of phospholipase A2 and cyclooxygenase were significantly increased in non-neoplastic mucosa in rats treated with 1-HA compared with those in control rats. The expressions in the neoplasms induced by 1-HA were also increased. Phospholipase A2, especially, was much higher in the neoplasms than in non-neoplastic mucosa. However, the expression of 5-lipoxygenase showed no change in the non-neoplastic mucosa and neoplasms of rats treated with 1-HA, compared with that in control rats. These findings suggest that the inflammation induced by 1-HA may be related to the metabolites through a cyclooxygenase pathway, which indicates a prostaglandin synthesis, but not through a lipoxygenase pathway, which indicates a leukotriene synthesis in arachidonic acid cascade.
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PMID:The mRNA overexpression of inflammatory enzymes, phospholipase A2 and cyclooxygenase, in the large bowel mucosa and neoplasms of F344 rats treated with naturally occurring carcinogen, 1-hydroxyanthraquinone. 758 82

Interleukin 1 (IL-1) induces prostanoid biosynthesis in endothelial cells by promoting cyclooxygenase expression, but little is known about its activity on the biosynthesis of hydroxyeicosatetraenoic acids (HETEs). We studied the effect of human recombinant IL-1 beta on the conversion of arachidonic acid (AA) to 15-HETE, a powerful inhibitor of the biosynthesis of proinflammatory eicosanoids. Cultured human umbilical vein endothelial cells were incubated with or without IL-1 beta prior to the addition of labeled AA. The eicosanoids produced were analyzed by RP-HPLC. Untreated cells produced little amounts of 15-HETE (6 +/- 3 pmol/10(6) cells), but IL-1 beta treated cells increased 15-HETE formation in a dose-dependent manner (4-5-fold at 10 U/ml IL-1). The production of HETEs by IL-1 beta was dependent on protein synthesis. Aspirin inhibited prostanoids, HHT and 11-HETE dose dependently, whereas it was unable to totally inhibit 15-HETE in IL-1 beta-treated cells (50-60%). Nordihydroguaiaretic acid, a general lipoxygenase inhibitor, preferably inhibited 15-HETE formation but also reduced the synthesis of the other eicosanoids in a dose-dependent manner. Indomethacin and ETYA completely suppressed prostanoids, 11-HETE and 15-HETE formation in resting and IL-1 beta-activated cells. Using specific 15-lipoxygenase oligonucleotides and the reverse transcriptase polymerase chain reaction technique, we were unable to evidence detectable 15-lipoxygenase mRNA both in resting and IL-1-activated endothelial cells. Overall, these results provide evidence that in human endothelial cells IL-1 beta increases 15-HETE production. Data strongly suggest that this effect is mediated by cyclooxygenase rather than 15-lipoxygenase activity or expression.
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PMID:Interleukin-1 increases 15-hydroxyeicosatetraenoic acid formation in cultured human endothelial cells. 769 Nov 82

The dementia associated with human immunodeficiency virus (HIV) is poorly understood. Dementia is accompanied by infection and activation of macrophage lineage cells in the brain and production of toxic products by these cells has been postulated to play a role in the pathogenesis of dementia. Eicosanoids are potential products of activated macrophages that can mediate cell injury. We measured the levels of prostaglandin E2 in the cerebrospinal fluid of HIV-positive individuals with dementia and/or myelopathy and compared these levels with those of HIV-negative patients with other neurological diseases and HIV-positive patients without dementia. Cerebrospinal fluid prostaglandin E2 levels were increased in dementia. This increase was associated with severity of dementia and correlated with cerebrospinal fluid levels of neopterin and beta 2-microglobulin. Prostaglandins F2 alpha and thromboxane B2, additional products of the cyclooxygenase pathway of arachidonic acid metabolism, were also elevated in dementia, but leukotriene C4, a product of the lipoxygenase pathway was not. Since synthesis of prostaglandins is regulated in part by the levels of inducible forms of cyclooxygenase, we measured the levels of cyclooxygenase-1 and 2 mRNAs in the brains of HIV-positive individuals with and without dementia by reverse transcriptase polymerase chain reaction. Levels of intact cyclooxygenase-1 mRNA were higher in the brains of demented individuals, but this did not reach statistical significance. These data demonstrate that prostaglandins are increased in the central nervous system in HIV-associated dementia and may play a role in the development of neurological dysfunction.
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PMID:Elevated central nervous system prostaglandins in human immunodeficiency virus-associated dementia. 791 4

The lipoxygenase (LO) pathway of arachidonate metabolism has been suggested to play a key role in atherosclerosis and in mediating several actions of angiotensin II (AII). However, the relationship between LO activation and factors linked to accelerated diabetic vascular disease such as hyperglycemia and AII is not known. We have investigated the effect of high glucose (HG; 25 mM) and AII on LO activity as well as LO protein and mRNA expression in porcine aortic vascular smooth muscle cells (PVSMCs). We observed that cells cultured in HG had significantly higher levels of the cell-associated LO products 12- and 15-hydroxyeicosatetraenoic acids (HETEs). AII added to cells grown in HG specifically further increased only cell-associated 12-HETE levels. Using immunoblot analysis and reverse transcriptase PCRs, we demonstrated the presence in PVSMCs of porcine leukocyte-type 12-LO protein and mRNA, respectively. Furthermore, the levels of both were markedly upregulated by AII as well as by HG. These studies suggest that enhanced 12-LO activity and expression are mechanisms for accelerated vascular disease produced by HG and AII in diabetes mellitus.
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PMID:Elevated glucose and angiotensin II increase 12-lipoxygenase activity and expression in porcine aortic smooth muscle cells. 850 39

Angiotensin II (Ang II) elicits an Ang II type 2 (AT2) receptor-mediated increase in delayed-rectifier K+ current (IK) in neurons cultured from newborn rat hypothalamus and brainstem. This effect involves a pertussis toxin (PTX)-sensitive Gi protein and is abolished by inhibition of serine and threonine phosphatase 2A (PP-2A). Here, we determined that Ang II stimulates [3H]arachidonic acid (AA) release from cultured neurons via AT2 receptors. This effect of Ang II was blocked by inhibition of phospholipase A2 (PLA2) and by PTX. Because AA and its metabolites are powerful modulators of neuronal K+ currents, we investigated the involvement of PLA2 and AA in the AT2 receptor-mediated stimulation of IK by Ang II. Single-cell reverse transcriptase (RT)-PCR analyses revealed the presence of PLA2 mRNA in neurons that responded to Ang II with an increase in IK. The stimulation of neuronal IK by Ang II was attenuated by selective inhibitors of PLA2 and was mimicked by application of AA to neurons. Inhibition of lipoxygenase (LO) enzymes significantly reduced both Ang II- and AA-stimulated IK, and the 12-LO metabolite of AA 12S-hydroxyeicosatetraenoic acid (12S-HETE) stimulated IK. These data indicate the involvement of a PLA2, AA, and LO metabolite intracellular pathway in the AT2 receptor-mediated stimulation of neuronal IK by Ang II. Furthermore, the demonstration that inhibition of PP-2A abolished the stimulatory effects of Ang II, AA, and 12S-HETE on neuronal IK but did not alter Ang II-stimulated [3H]-AA release suggests that PP-2A is a distal event in this pathway.
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PMID:Angiotensin II type 2 receptor stimulation of neuronal delayed-rectifier potassium current involves phospholipase A2 and arachidonic acid. 942 10

The lipoxygenase (LO) pathway has been implicated as an important mediator of chronic glucose and platelet-derived growth factor (PDGF)-induced effects in the vascular system. Endothelial cells treated with 12LO products or cultured in high glucose showed enhanced monocyte adhesion, an important step in atherogenesis. We have previously reported that PDGF increased HETE levels in porcine aortic smooth muscle cells. Although several pharmacological inhibitors to the LO pathway are available, most lack specificity and may harbor undesirable side effects. Therefore, we developed a recombinant adenovirus expressing a hammerhead ribozyme (AdRZ) targeted against the porcine leukocyte-type 12LO mRNA to investigate the involvement of LO in glucose- and PDGF-mediated effects in vascular cells. Infection of porcine aortic endothelial cells with AdRZ reduced the level of glucose-enhanced 12LO mRNA expression as determined by quantitative, real-time reverse transcriptase-polymerase chain reaction. Reverse-phase HPLC and RIA analysis also revealed a corresponding decrease in glucose-stimulated 12HETE production in both the cellular and supernatant fractions. In the ribozyme-treated porcine aortic endothelial cells, there was marked inhibition of high glucose-stimulated monocyte adhesion. Infection with AdRZ also reduced PDGF-induced porcine aortic smooth muscle cell migration by approximately 50%. These studies demonstrate the efficacy of recombinant adenovirus expressing 12LO ribozyme in studying the effects of 12LO in vascular wall cells. They document an important role for the 12LO pathway in regulating inflammatory changes in endothelial cells and smooth muscle cells.
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PMID:Adenoviral delivery of a leukocyte-type 12 lipoxygenase ribozyme inhibits effects of glucose and platelet-derived growth factor in vascular endothelial and smooth muscle cells. 1130 87

Previous studies have indicated that arachidonic acid and its lipoxygenase (LO) metabolites play a role in the post-receptor effects of gonadotropin-releasing hormone (GnRH) but the exact role and nature of these putative eicosanoids remain unclear. The potential role of arachidonic acid and LO in GnRH receptor-mediated signaling was investigated in the LbetaT2 gonadotrope cell line, which expresses gonadotropins (LH and FSH) and GnRH-receptor mRNAs. Western immunobloting of LbetaT2 cell extracts, performed with a murine leukocyte polyclonal antibody against 12-LO, showed a 70-kD band, suggesting the presence of 12-LO protein in these cells. GnRH nearly doubled the release of 12-hydroeicosatetraenoic acid, a product of the 12-LO enzyme, within 10 min. A specific reverse transcriptase polymerase chain reaction with a set of primers based on the reported sequence of rat brain 12-LO yielded a 170-bp band which showed 100% homology with the expected rat brain 12-LO sequence. Exposure of LbetaT2 cells to pulsatile GnRH treatment (10 nM, 90-min interpulse, one and three pulses) led to a approximately 3-fold increase in 12-LO mRNA levels. In conclusion, we provide evidence for the presence of a 12-LO enzyme in LbetaT2 cells, the expression and activity of which are increased by short-term/pulsatile exposure to GnRH. LbetaT2 cells represent a potential model to further study the involvement of 12-LO in GnRH receptor signaling.
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PMID:Gonadotropin-releasing hormone activates the 12-lipoxygenase pathway in the LbetaT2 gonadotrope cell line. 1280 74

Potato (Solanum tuberosum) plants are rich in 9-lipoxygenase, which converts linoleic acid and alpha-linolenic acid to 9S-hydroperoxy-10E,12Z-octadecadienoic acid (9-HPOD) and 9S-hydroperoxy-10E,12Z,15Z-octadecatrienoic acid (9-HPOT) respectively. The allene oxide synthase (AOS) involved in 9-HPOD/9-HPOT metabolism in potato, however, has not been characterized in detail. We cloned a cDNA encoding a novel AOS from potato sprouts by reverse transcriptase-PCR based on a partial sequence in the EST database. This AOS was successfully expressed in the yeast Pichia pastoris, and purified using Ni-NTA resin. The recombinant enzyme metabolized 9-HPOD, 9-HPOT, 13-HPOD, and 13-HPOT with reaction efficiencies of 2.5 x 10(7), 1.0 x 10(7), 2.5 x 10(6), and 7.6 x 10(6) M(-1) s(-1) respectively. The alpha-ketol formed from 9-HPOD was composed mainly of the 9R-enatimomer (90%). Besides sprouts, the mRNA of this AOS was detected in buds, flowers, and stems, but not in leaves, tubers, or roots of mature plants, suggesting that this enzyme has a tissue-specific function.
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PMID:Molecular cloning, functional expression, and tissue distribution of a potato sprout allene oxide synthase involved in a 9-lipoxygenase pathway. 1696 Mar 83

Patatin-like genes have recently been cloned from several plant species and found to be involved in stress responses and development. In previous work, we have shown that a patatin-like gene encoding a galactolipid acyl hydrolase (EC 3.1.1.26) was stimulated by drought in the leaves of the tropical legume, Vigna unguiculata L. Walp. The aim of the present work was to study the expression of patatin-like genes in Arabidopsis thaliana under water deficit. Expression of six genes was studied by reverse transcriptase polymerase chain reaction in leaves of plants submitted to progressive drought stress induced by withholding water and also in different plant organs. Three genes, designated AtPAT IIA, AtPAT IVC and AtPAT IIIA, were shown to be upregulated by water deficit but with different kinetics, while the other patatin-like genes were either constitutive or not expressed in leaves. The accumulation of transcripts of AtPAT IIA in the early stages of the drought treatment was coordinated with the upregulation of lipoxygenase and allene oxide synthase genes. AtPAT IIA expression was also induced by wounding and methyl jasmonate treatments. The in vitro lipolytic activity toward monogalactosyldiacylglycerol, digalactosyldiacylglycerol, phosphatidylcholine and phosphatidylglycerol was confirmed by producing the recombinant protein ATPAT IIA in insect cells. The analysis of free fatty acid pools in drought-stressed leaves shows an increase in the relative amounts of trans-3-hexadecenoic acid at the beginning of the treatment followed by a progressive accumulation of linoleic and linolenic acids. The possible roles of AtPAT IIA in lipid signaling and membrane degradation under water deficit are discussed.
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PMID:Effects of progressive drought stress on the expression of patatin-like lipid acyl hydrolase genes in Arabidopsis leaves. 1843 22


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