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)

In the present study, we developed a very sensitive, semiquantitative assay based on the reverse transcriptase-coupled polymerase chain reaction to measure, in a region-selective manner, mRNA expression patterns within the brain for microsomal epoxide hydrolase and several cytochrome P-450s (P-450s) known to be induced by prototypic agents in other tissues. The P-450s assessed included the polyaromatic hydrocarbon-inducible CYP1A1 and CYP1A2 systems, together with the phenobarbital-inducible P-450s, CYP2B1, CYP2B2, CYP3A1, which were examined 18 hr after a single intraperitoneal dose of the respective inducing agents. Highly region-specific patterns of expression were evident for P-450 mRNAs within the rat brain. In the control, uninduced brain, CYP1A1 mRNAs were readily detected in the striatum and in the hypothalamus, and to a lesser extent in the other regions examined. The regional pattern of expression was similar for CYP1A2; however, a major difference was noted in the olfactory bulbs, characterized by a relatively high level of CYP1A2 mRNA but correspondingly low levels of CYP1A1. Within the brain regions examined, the highest content of CYP2B1 and CYP2B2 mRNAs were present in the striatum and in the cerebellum, whereas CYP3A1 levels varied only slightly across the respective regions. In contrast to the P-450s, microsomal epoxide hydrolase mRNAs were expressed at relative homogeneous amounts throughout the brain. beta-Naphthoflavone markedly increased the CYP1A1 and CYP1A2 mRNA contents of each brain region investigated, although this agent did not affect levels of epoxide hydrolase. At 18 hr post-treatment with phenobarbital, an optimal time period for hepatic induction, brain expression was characterized by a complex pattern of effects, with increased levels noted for CYP2B1 mRNA content in the medulla oblongata, midbrain, and cortex, but decreased contents measured in the cerebellum, the hypothalamus, and the striatum. In each of these respective regions, CYP2B2 content was profoundly decreased whereas epoxide hydrolase expression was slightly increased by the same treatment. These results establish that the central nervous system actively expresses a number of different biotransformation gene products in a regional specific and inducer-dependent manner, and suggest that for tissues exhibiting low regenerative capacity, like the brain, such reactions are likely to be of critical toxicological significance.
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PMID:Regional distribution and expression modulation of cytochrome P-450 and epoxide hydrolase mRNAs in the rat brain. 824 22

Third-passage human umbilical vein endothelial cells (HUVECs) or fifth-passage human aortic endothelial cells (HAECs) were subjected to 25 dynes/cm(2) for 24 h in a parallel-plate flow system. Matched control cells were maintained in static conditions. Total RNA was isolated and pooled from six to eight slides per experiment. Changes in gene expression were analyzed by Northern blots and reverse transcriptase-polymerase chain reaction. Fold changes were normalized to glyceraldehyde phosphate dehydrogenase (GAPDH) values. In HUVECs, arterial levels of shear stress increased mRNA expression of Cytochrome P450 1A1 (CYP1A1) 10.8 +/- 2.1-fold, and CYP1B1 23.1 +/- 3.7-fold; whereas connective tissue growth factor (CTGF) expression was unchanged and endothelin-1 (ET-1) mRNA expression was decreased 0.7 +/- 0.05-fold. The authors determined whether these changes were induced by beta-naphthoflavone, a polyaromatic hydrocarbon, and whether they occurred in HAECs. beta-Naphthoflavone up-regulated CYP1A1 18.3 +/- 4.2-fold, and CYP1B1 4.1 +/- 0.3-fold in HUVECs. Shear stress up-regulated CYP1A1 6.3 +/- 0.4-fold and CYP1B1 51.1 +/- 2.1-fold in HAECs. In addition, the authors examined CYP1A1 and CYP1B1 proteins translated from these genes. Experiments identical to those described above were performed and the cells harvested for protein identification by Western blot of CYP1A1 and CYP1B1. Protein levels of CYP1A1 in HUVECs were up-regulated under shear stress, whereas protein levels of CYP1B1 were not.
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PMID:Endothelial cell cytochrome P450 1A1 and 1B1: up-regulation by shear stress. 1520 74