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)

To determine which alpha 2-adrenergic receptor subtypes are present in primary afferent and sympathetic postganglionic neurons we have performed in situ hybridization and immunohistochemistry experiments on rat dorsal root and superior cervical ganglia. Reverse transcriptase polymerase chain reaction was used as a preliminary screen for the presence of mRNA encoding alpha 2-adrenergic subtypes in dorsal root and superior cervical ganglia; polymerase chain reaction primers amplified distinct regions of the rat alpha 2A-(RG20), alpha 2B-(RNG) and alpha 2C-(RG10) adrenergic receptor subtypes in mRNA extracted from lumbar dorsal root and superior cervical ganglia. To localize receptors to cell types in the ganglia, in situ hybridization was performed on cryosections of dorsal root and superior cervical ganglia with oligonucleotide probes designed to distinguish between mRNA encoding for alpha 2-adrenergic receptor subtypes. Immunohistochemistry was performed with a polyclonal antibody against the alpha 2A-adrenergic receptor subtype. Our results with reverse transcriptase polymerase chain reaction indicate that all three alpha 2-adrenergic receptor subtypes are expressed in dorsal root and superior cervical ganglia. Data from the in situ hybridization experiments indicated that the mRNA detected with the reverse transcriptase polymerase chain reaction was present in neuronal cell bodies, except for the mRNA encoding the alpha 2A-adrenergic receptor which was not detectable in dorsal root ganglia. The distribution of mRNA encoding alpha 2B- and alpha 2C-adrenergic receptor subtypes among dorsal root ganglion neurons and alpha 2A-, alpha 2B- and alpha 2C-adrenergic receptor subtypes among superior cervical ganglion neurons suggests that multiple adrenergic receptor subtypes are present in a single neuron. Neuronal cell bodies in both the dorsal root and superior cervical ganglion consistently demonstrated alpha 2A-adrenergic receptor-like immunoreactivity. The apparent co-expression of multiple alpha 2-adrenergic receptor subtypes in dorsal root and superior cervical ganglion neurons enables a single transmitter to produce a number of effects in the same neuron; which receptors are functionally active may vary with the presence of nerve injury, inflammation or other physiological and pathophysiological conditions.
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PMID:Alpha 2-adrenergic receptor subtypes in rat dorsal root and superior cervical ganglion neurons. 906 29

Induction of hepatic phase I/II detoxification enzymes and alternative excretory pumps may limit hepatocellular accumulation of toxic biliary compounds in cholestasis. Because the nuclear xenobiotic receptors constitutive androstane receptor (CAR) and pregnane X receptor (PXR) regulate involved enzymes and transporters, we aimed to induce adaptive alternative pathways with different CAR and PXR agonists in vivo. Mice were treated with the CAR agonists phenobarbital and 1,4-bis-[2-(3,5-dichlorpyridyloxy)]benzene, as well as the PXR agonists atorvastatin and pregnenolone-16alpha-carbonitrile. Hepatic bile acid and bilirubin-metabolizing/detoxifying enzymes (Cyp2b10, Cyp3a11, Ugt1a1, Sult2a1), their regulatory nuclear receptors (CAR, PXR, farnesoid X receptor), and bile acid/organic anion and lipid transporters (Ntcp, Oatp1,2,4, Bsep, Mrp2-4, Mdr2, Abcg5/8, Asbt) in the liver and kidney were analyzed via reverse-transcriptase polymerase chain reaction and Western blotting. Potential functional relevance was tested in common bile duct ligation (CBDL). CAR agonists induced Mrp2-4 and Oatp2; PXR agonists induced only Mrp3 and Oatp2. Both PXR and CAR agonists profoundly stimulated bile acid-hydroxylating/detoxifying enzymes Cyp3a11 and Cyp2b10. In addition, CAR agonists upregulated bile acid-sulfating Sult2a1 and bilirubin-glucuronidating Ugt1a1. These changes were accompanied by reduced serum levels of bilirubin and bile acids in healthy and CBDL mice and by increased levels of polyhydroxylated bile acids in serum and urine of cholestatic mice. Atorvastatin significantly increased Oatp2, Mdr2, and Asbt, while other transporters and enzymes were moderately affected. In conclusion, administration of specific CAR or PXR ligands results in coordinated stimulation of major hepatic bile acid/bilirubin metabolizing and detoxifying enzymes and hepatic key alternative efflux systems, effects that are predicted to counteract cholestasis.
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PMID:CAR and PXR agonists stimulate hepatic bile acid and bilirubin detoxification and elimination pathways in mice. 1602 8

In this study, the P2 receptor-mediated modulation of [3H]glutamate and [3H]noradrenaline release were examined in rat spinal cord slices. Adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP), and 2-methylthioadenosine 5'-diphosphate (2-MeSADP) decreased the electrical stimulation-evoked [3H]glutamate efflux with the following order of potency: ADP>2-MeSADP>ATP. The effect of ATP was antagonized by suramin (300microM), the P2Y12,13 receptor antagonist 2-methylthioadenosine 5'-monophosphate (2-MeSAMP, 10microM), and partly by 4-[[4-Formyl-5-hydroxy-6-methyl-3-[(phosphonooxy)methyl]-2-pyridinyl]azo]-1,3-benzenedisulfonic acid (PPADS, 30microM) and the P2Y1 receptor antagonist 2'-deoxy-N6-methyladenosine 3',5'-diphosphate (MRS 2179, 10muM). ATP, ADP and 2-MeSADP also decreased evoked [3H]noradrenaline outflow; the order of agonist potency was ADP> or =2-MeSADP>ATP. The effect of ATP was reversed by 2-MeSAMP (10microM), and partly by MRS 2179 (10microM). By contrast, 2-methylthioadenosine-5'-triphosphate (2-MeSATP, 10-300microM) increased resting and electrically evoked [3H]glutamate and [3H]noradrenaline efflux, and this effect was prevented by the P2X1 receptor selective antagonist 4,4',4'',4'''-[carbonylbis[imino-5,1,3-benzenetriyl bis (carbonyl-imino)]] tetrakis (benzene-1,3-disulfonic acid) octasodium salt (NF449, 100nM). Reverse transcriptase polymerase chain reaction (RT-PCR) analysis revealed that mRNAs encoding P2Y12 and P2Y13 receptors are expressed in the brainstem, whereas P2Y13 but not P2Y12 receptor mRNA is present in the dorsal root ganglion and spinal cord. P2Y1 receptor expression in the spinal cord is also demonstrated at the protein level. In conclusion, inhibitory P2Y and facilitatory P2X1-like receptors, involved in the regulation of glutamate (P2Y13 and/or P2Y1) and noradrenaline (P2Y13 and/or P2Y1, P2Y12) release have been identified, which provide novel target sites for analgesics acting at the spinal cord level.
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PMID:Modulation of neurotransmitter release by P2X and P2Y receptors in the rat spinal cord. 1806

A bacterium designated strain BD-a59, able to degrade all six benzene, toluene, ethylbenzene, and o-, m-, and p-xylene (BTEX) compounds, was isolated by plating gasoline-contaminated sediment from a gasoline station in Geoje, Republic of Korea, without enrichment, on minimal salts basal (MSB) agar containing 0.01% yeast extract, with BTEX as the sole carbon and energy source. Taxonomic analyses showed that the isolate belonged to Pseudoxanthomonas spadix, and until now, the genus Pseudoxanthomonas has not included any known BTEX degraders. The BTEX biodegradation rate was very low in MSB broth, but adding a small amount of yeast extract greatly enhanced the biodegradation. Interestingly, degradation occurred very quickly in slurry systems amended with sterile soil solids but not with aqueous soil extract. Moreover, if soil was combusted first to remove organic matter, the enhancement effect on BTEX biodegradation was lost, indicating that some components of insoluble organic compounds are nutritionally beneficial for BTEX degradation. Reverse transcriptase PCR-based analysis of field-fixed mRNA revealed expression of the tmoA gene, whose sequence was closely related to that carried by strain BD-a59. This study suggests that strain BD-a59 has the potential to assist in BTEX biodegradation at contaminated sites.
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PMID:Influence of soil components on the biodegradation of benzene, toluene, ethylbenzene, and o-, m-, and p-xylenes by the newly isolated bacterium Pseudoxanthomonas spadix BD-a59. 1883 99

Increasingly, molecular biological tools, most notably quantitative polymerase chain reaction (qPCR), are being employed to provide a more comprehensive assessment of bioremediation of petroleum hydrocarbons and fuel oxygenates. While qPCR enumeration of key organisms or catabolic genes can aid in site management decisions, evaluation of site activities conducted to stimulate biodegradation would ideally include a direct measure of gene expression to infer activity. In the current study, reverse-transcriptase (RT) qPCR was used to monitor gene expression to evaluate the effectiveness of an oxygen infusion system to promote biodegradation of BTEX and MTBE. During system operation, dissolved oxygen (DO) levels at the infusion points were greater than 30 mg/L, contaminant concentrations decreased, and transcription of two aromatic oxygenase genes and Methylibium petroleiphilum PM1-like 16S rRNA copies increased by as many as 5 orders of magnitude. Moreover, aromatic oxygenase gene transcription and PM1 16s rRNA increased at downgradient locations despite low DO levels even during system operation. Conversely, target gene expression substantially decreased when the system was deactivated. RT-qPCR results also corresponded to increases in benzene and MTBE attenuation rates. Overall, monitoring gene expression complemented traditional groundwater analyses and conclusively demonstrated that the oxygen infusion system promoted BTEX and MTBE biodegradation.
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PMID:Monitoring gene expression to evaluate oxygen infusion at a gasoline-contaminated site. 2068 21

A series of novel N-(3-substituted aryl/alkyl-4-oxo-1,3-thiazolidin-2-ylidene)-4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamides 2a-e were synthesized by the addition of ethyl a-bromoacetate and anhydrous sodium acetate in dry ethanol to N-(substituted aryl/alkylcarbamothioyl)-4-[5-(4-methylphenyl)-3-(trifluoro-methyl)-1H-pyrazol-1-yl]benzene sulfonamides 1a-e, which were synthesized by the reaction of alkyl/aryl isothiocyanates with celecoxib. The structures of the isolated products were determined by spectral methods and their anti-inflammatory, analgesic, antioxidant, anticancer and anti-HCV NS5B RNA-dependent RNA polymerase (RdRp) activities evaluated. The compounds were also tested for gastric toxicity and selected compound 1a was screened for its anticancer activity against 60 human tumor cell lines. These investigations revealed that compound 1a exhibited anti-inflammatory and analgesic activities and further did not cause tissue damage in liver, kidney, colon and brain compared to untreated controls or celecoxib. Compounds 1c and 1d displayed modest inhibition of HCV NS5B RdRp activity. In conclusion, N-(ethylcarbamothioyl)-4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (1a) may have the potential to be developed into a therapeutic agent.
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PMID:Synthesis and characterization of celecoxib derivatives as possible anti-inflammatory, analgesic, antioxidant, anticancer and anti-HCV agents. 2351 1