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)

Extracts derived from Albizia amara were found to demonstrate activity in a recently developed hplc system designed to detect compounds capable of interacting with DNA. Further investigation led to the procurement of four sets of alkaloid isolates X1-X4 that were found to be macrocyclic pithecolobine alkaloids. All four isolates interacted with calf thymus DNA and were generally cytotoxic with a battery of cultured mammalian cells. As determined with Salmonella typhimurium strain TM677, isolates X1 and X3 were bactericidal, but not mutagenic. Isolate X1 was found to inhibit the catalytic activity of DNA polymerase, RNA polymerase, and HIV-1 reverse transcriptase. With DNA polymerase, the reaction was shown to be inhibited in a manner that was competitive with respect to DNA. In addition, isolate X1 inhibited each of the following: platelet aggregation, human lymphocyte transformation, phorbol-ester-induced chemiluminescence with human granulocytes, and cyclooxygenase activity. Detection of these alkaloids on the basis of their interaction with DNA exemplifies the validity of this approach.
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PMID:Biological activity of novel macrocyclic alkaloids (budmunchiamines) from Albizia amara detected on the basis of interaction with DNA. 172 78

To assess regulation of constitutive prostaglandin G/H synthase (PGHS-1) by interleukin-1 (IL-1) in osteoblastic MC3T3-E1 cells, we compared analysis by competitive reverse transcriptase-polymerase chain reaction (RT-PCR) with Northern blot analysis. Using RT-PCR, IL-1 increased PGHS-1 mRNA levels by 1.84 +/- 0.10 or 2.07 +/- 0.17, depending on the method of calculation. Using Northern blot analysis, the effect of IL-1 on PGHS-1 mRNA levels was more variable, and the variability was increased by normalization of PGHS-1 mRNA levels to the housekeeping genes, beta-actin and glyceraldehyde phosphate dehydrogenase (GAPDH), because their mRNA levels were also regulated by IL-1. We conclude that competitive RT-PCR is a reproducible and accurate method for studying small changes in mRNA levels.
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PMID:Measurement of interleukin-1 stimulated constitutive prostaglandin G/H synthase (cyclooxygenase) mRNA levels in osteoblastic MC3T3-E1 cells using competitive reverse transcriptase polymerase chain reaction. 752 76

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

To elucidate the mechanism for the selective inhibition of prostaglandin E2 (PGE2) production in inflammatory tissue by T-614 (3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-o ne), its effects on both the activity and the induction of cyclooxygenase (COX)-2 were investigated in vitro. T-614 inhibited the activity of purified COX-2 enzyme (IC50: 7.7 micrograms/ml), but was inactive against both COX-1 activities of microsomal and purified enzymes (IC50: > 300 micrograms/ml). On the other hand, when the inhibition of PGE2 production by T-614 was examined in the cultured fibroblasts stimulated with bradykinin, T-614 at 1 microgram/ml or less inhibited PGE2 release more effectively than that in the above cell-free system. Therefore, we examined which of the COX enzymes was expressed in bradykinin-stimulated fibroblasts by using both the reverse transcriptase-polymerase chain reaction (RT-PCR) and Northern blot analyses. As a result, COX-1 mRNA was constitutively expressed in the cells, whereas COX-2 mRNA was not detected without stimulation with bradykinin, but was expressed within 30 min when stimulated. Furthermore, it was found that the addition of T-614 reduced the COX-2 mRNA levels in 30 min after stimulation. These studies suggest that at least some of inhibitory effects of T-614 on prostanoids production are mediated by the synergy of the inhibition of COX-2 activity and the inhibition of induction, and such an action of T-614 may explain the pharmacological properties of this drug.
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PMID:T-614, a novel antirheumatic drug, inhibits both the activity and induction of cyclooxygenase-2 (COX-2) in cultured fibroblasts. 765 Aug 64

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

Prostaglandin H2 (PGH2 [endoperoxide]) is an immediate product of prostaglandin H (PGH) synthase activity (cyclooxygenase) and a likely candidate to mediate endothelium-dependent contractions evoked by acetylcholine in the aorta of the spontaneously hypertensive rat (SHR). Experiments were designed to investigate whether or not endothelium-dependent contractions were associated with an increased expression of PGH synthase, an augmented acetylcholine-induced release of PGH2, and/or a hypersensitivity of the smooth muscle to endoperoxides in SHR aorta compared with normotensive Wistar-Kyoto (WKY) aorta. In SHR aorta, endothelium-dependent contractions to acetylcholine were abolished by tenidap (10(-8) mol/L), a preferential PGH synthase-1 inhibitor, but slightly impaired by NS-398 (10(-6) mol/L), a preferential PGH synthase-2 inhibitor. PGH synthase-1 expression, which was evaluated by both reverse transcriptase-polymerase chain reaction and Western blotting, was about twofold greater in preparations with endothelium from SHR than from WKY rats. There was no difference in PGH synthase-1 expression between preparations with and those without endothelium in both strains. In SHR but not WKY aortas, acetylcholine (10(-5) mol/L, 5 minutes) caused a significant endothelium-dependent release of PGH2 as measured by gas chromatography/mass spectrometry. PGH2 evoked more potent contractions in rings without endothelium from SHR than from WKY rats, whereas the thromboxane analogue U46619 and prostaglandin F2 alpha caused a comparable response in both preparations. These results show that endothelium-dependent contractions to acetylcholine in SHR aorta are associated with a greater expression of PGH synthase-1, a significant release of PGH2, and a hypersensitivity of the smooth muscle to the endoperoxide.
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PMID:Endothelium-dependent contractions are associated with both augmented expression of prostaglandin H synthase-1 and hypersensitivity to prostaglandin H2 in the SHR aorta. 775 54

To examine the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on thymic gene expression in vitro, freshly isolated rat thymocytes were incubated with 10 nM TCDD, and reverse transcriptase polymerase chain reaction experiments were performed using primers specific for prostaglandin G/H synthase (PGHS) and glyceraldehyde 3-phosphate dehydrogenase. TCDD selectively repressed PGHS gene expression, with maximal inhibition occurring within 60 min. Gel retardation assays demonstrated that dioxin transiently induced binding of the ubiquitous transcription factor NF kappa B to its cognate response element at early time points. However, TCDD had little ability to induce transformation of the Ah receptor to the xenobiotic responsive element in thymic cytosol. These results indicate that TCDD exerts changes in thymocyte gene expression prior to inducing toxicity.
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PMID:2,3,7,8-Tetrachlorodibenzo-p-dioxin-mediated gene expression in the immature rat thymus. 782 58

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

A second prostaglandin G/H synthase (PGHS-2), encoded by a gene separate from that for the original PGHS (PGHS-1), has recently been identified. We have shown that PGHS-2 is expressed in cultured mouse calvariae and have compared regulation of PGHS-2 and PGHS-1 messenger RNA (mRNA) levels. PGHS-2 mRNA was not detectable in freshly isolated bones, but was induced during culture and further stimulated by interleukin-1 (IL-1) and PTH. Both factors also increased PGHS-2 protein levels. Changes in medium prostaglandin E2 (PGE2) production correlated with increases in PGHS-2 mRNA levels. However, with IL-1, PGE2 production was increased more than PGHS-2 mRNA levels (treated/control ratio, 3.4 and 1.5, respectively), whereas with PTH there was a closer correspondence (2.0 and 2.1). Cortisol reduced PTH-stimulated PGE2 production (treated/control ratio decreased from 3.1 to 0.2) more than PGHS-2 mRNA levels (2.8 to 0.8). In the presence of exogenous arachidonic acid, changes in PGHS-2 mRNA levels with IL-1, PTH, and cortisol correlated closely with changes in PGE2 production. PGE2 itself increased PGHS-2 mRNA, and nonsteroidal antiinflammatory drugs decreased PGHS-2 mRNA levels by 80%. In contrast, PGHS-1 mRNA was expressed constitutively and was not affected by IL-1, PTH, or cortisol when measured by competitive reverse transcriptase-polymerase chain reaction. We conclude that regulation of PGE2 production is predominantly through PGHS-2, rather than PGHS-1; that IL-1 and cortisol may also regulate arachidonic acid release; and that PGE2 may amplify its own production through stimulation of PGHS-2.
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PMID:Regulation of the two prostaglandin G/H synthases by parathyroid hormone, interleukin-1, cortisol, and prostaglandin E2 in cultured neonatal mouse calvariae. 807 Mar 58

The rate-limiting step in the formation of prostanoids is the conversion of arachidonic acid to prostaglandin H2 by cyclooxygenase, also known as prostaglandin G/H synthase/cyclooxygenase. Two forms of cyclooxygenase have been characterized: a ubiquitously expressed form (COX-1) and a recently described second form (COX-2) inducible by various factors including mitogens, hormones, serum and cytokines. Here we quantitate by the reverse transcriptase-polymerase chain reaction (RT-PCR) the expression of COX-1 and COX-2 mRNA in human tissues including lung, uterus, testis, brain, pancreas, kidney, liver, thymus, prostate, mammary gland, stomach and small intestine. All tissues examined contained both COX-1 and COX-2 mRNA and could be grouped according to the level of COX mRNA expression. The highest levels of COX mRNAs were detected in the prostate where approximately equal levels of COX-1 and COX-2 transcripts were present. In the lung high levels of COX-2 were observed whereas COX-1 mRNA levels were about 2-fold lower. An intermediate level of expression of both COX-1 and COX-2 mRNA was observed in the mammary gland, stomach, small intestine, and uterus. The lowest levels of COX-1 and COX-2 mRNA were observed in the testis, pancreas, kidney, liver, thymus, and brain.
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PMID:Expression of mRNA for cyclooxygenase-1 and cyclooxygenase-2 in human tissues. 836 85


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