Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Indomethacin blocks the biosynthesis of vesicular stomatitis virus (VSV) at the level of primary transcription, RNA replication, and protein synthesis (P. K. Mukherjee and R. W. Simpson (1985), Virology 140, 188-191). Nucleocapsids of infecting virus particles recovered from indomethacin-treated cells were analyzed for in vitro transcriptase activity. Incorporation of [3H]UTP in mixtures containing nucleocapsids from HEp-2 cells pretreated with 10(-3) M indomethacin was inhibited approximately 80% compared to control reactions containing nucleocapsids from untreated infected cells. The level of inhibition of in vitro transcriptase activity of viral nucleocapsids from drug-treated cultures varied according to the cell line used for infection. After indomethacin removal, cells regained their ability to produce enzymatically competent viral-transcribing complexes unless they were subsequently exposed to metabolic inhibitors such as actinomycin D or alpha-amanitin. Enzymatically defective nucleocapsids from indomethacin-treated cells showed enhanced in vitro transcriptase activity in the presence of modulators of prostaglandins and cyclic nucleotides. Electrophoretic analysis of product from in vitro transcriptase reactions revealed that these defective nucleocapsids are unable to synthesize VSV messenger RNA or normal size leader RNA species but only smaller transcripts of undetermined identity.
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PMID:Transcriptionally defective nucleocapsids of vesicular stomatitis virus from cells treated with indomethacin. 302 67

Growth factors and prostaglandins protect the gastric mucosa against stress-induced lesions but their role in the recovery of the mucosa from these lesions has been little studied. We evaluated gastric mucosa lesions, gastric blood flow, mucosal generation of prostaglandin E2 and mucosal gene expression of epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) as well as constitutive prostaglandin cyclooxygenase-1 and inducible cyclooxygenase-2 and the effect of the inhibition of these enzymes on the recovery of mucosa from the stress-induced lesions. Rats were exposed to 3.5 h of water immersion and restraint stress and killed at 0, 2, 4, 6, 8, 12 and 24 h after stress. The number of gastric lesions was determined and gastric blood flow was measured by H2-gas clearance. Gastric acid secretion was tested in separate gastric fistula rats. Gastric mucosa biopsies were taken for determination of immunoreactive EGF and TGF alpha. Expression of EGF and TGF alpha mRNA and cyclooxygenase-1 and cyclooxygenase-2 mRNA was also determined by reverse-transcriptase polymerase chain reaction. The number of gastric lesions induced by 3.5 h stress averaged approximately 20 per rat and declined significantly at 2, 4, 6, 8 and 12 h, to disappear almost completely after 24 h. This was accompanied by a gradual rise in gastric blood flow, mucosal generation of prostaglandin E2 and mucosal EGF and TGF alpha contents, while the increased gastric acid secretion returned to normal. In the intact mucosa, EGF mRNA was not detected but TGF alpha mRNA was found in measurable amounts. Following exposure to stress, the expression of both these factors was significantly increased. Similarly, the expression of cyclo-oxygenase-1 and cyclooxygenase-2 mRNA was detected in the oxyntic mucosa at all time intervals after exposure to stress. Indomethacin (5 mg/kg i.p.), an inhibitor of cyclooxygenase-1 and cyclooxygenase-2, and meloxicam (1 mg/kg i.p.), an inhibitor of cyclooxygenase-2, both prolonged the healing of stress lesions and reduced the gastric blood flow, while enhancing gastric acid secretion at all times tested. We conclude that healing of stress lesions results in the restoration gastric blood flow and mucosal prostaglandin generation and that these effects are accompanied by overexpression of EGF and TGF alpha as well as cyclooxygenase-1 and cyclooxygenase-2 mRNA and by increased biosynthesis of gastroprotective prostaglandin.
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PMID:Activation of genes for growth factors and cyclooxygenases in rat gastric mucosa during recovery from stress damage. 954 93

The objective of this study was to determine the expression and activity of multidrug resistance-associated protein (MRP1) in a human airway epithelial cell line (Calu-1) and to further assess whether budesonide, a potent antiasthma corticosteroid, alters the expression and activity of MRP1 in these cells. Reverse transcriptase polymerase chain reaction (RT-PCR) and the Western blot analysis demonstrated the MRP1 mRNA and MRP1 protein in Calu-1 cells. Indomethacin, probenecid, and verapamil significantly enhanced the fluorescein accumulation and reduced the fluorescein efflux, consistent with the MRP1 activity in the Calu-1 cells. Following 14-day budesonide treatment, fluorescein accumulation increased and fluorescein efflux decreased, consistent with the inhibition of MRP1 activity by budesonide. At a concentration (10 microM) devoid of cytotoxicity, budesonide treatment decreased MRP1 mRNA and MRP1 protein expression in Calu-1 cells by 38% and 42%, respectively. In addition, budesonide (10 microM) enhanced the sensitivity of the MRP1 overexpressing COR-L23R cells to vincristine, suggesting the chemosensitizing effect of budesonide. Thus, budesonide inhibits MRP1 expression and may be useful as a chemosensitizer in tumor chemotherapy.
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PMID:Budesonide reduces multidrug resistance-associated protein 1 expression in an airway epithelial cell line (Calu-1). 1186 33