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)

Incinerator workers are exposed to polycyclic aromatic hydrocarbons (PAHs) and dioxins in workplace. Previous studies indicated that aryl hydrocarbon receptor activation, following by increased cytochrome P4501A1 (CYP1A1) and 1B1 (CYP1B1) activity and expressions, was required for PAHs and dioxin induced toxicities. This study investigated whether municipal waste incinerator workers with frequent exposure to PAHs/dioxins in fly/bottom ash had increased CYP1A1 and CYP1B1 expressions in peripheral leukocytes and assessed whether CYP1B1*3 polymorphism modified the association between PAHs/dioxins exposure and CYP1B1 expressions. Based on job contents and time-activity profiles, 112 workers were classified into high exposure, medium exposure and control groups. CYP1A1 and CYP1B1 gene expressions in workers' leukocytes were determined with the real-time reverse transcriptase polymerase chain reaction method. After taking into account age, gender and smoking in the multiple regression analyses, CYP1B1, but not CYP1A1, levels were significantly higher in the high and medium exposure groups than in the control group, and there was a statistically significant interaction between exposure group and CYP1B1 genotype. These results suggested that CYP1B1 gene expression could be a potential biomarker of biologically effective dose for occupational exposure to PAHs/dioxins and CYP1B1*3 polymorphism modified effects of occupational exposures on CYP1B1 expression.
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PMID:Increased cytochrome P4501B1 gene expression in peripheral leukocytes of municipal waste incinerator workers. 1609 93

There is significant human exposure to polycyclic aromatic hydrocarbons (PAHs), many of which are bioactivated by the cytochrome P450 (P450) 1A family of enzymes to metabolites that are capable of covalently binding to DNA, a critical step in the initiation of carcinogenesis. We reported earlier that exposure of rats to 3-methylcholanthrene (MC) causes sustained induction of hepatic cytochrome P4501A expression for up to 45 days. Here, we tested the hypothesis that MC elicits persistent induction of other genes that are regulated by the Ah receptor (AHR). Female Sprague-Dawley rats were treated with MC (100 micromol/kg) ip once daily for 4 days, and gene expression patterns were investigated using total liver RNA isolated from animals at 1, 15, and 28 days after MC withdrawal. Gene expression was studied by cDNA microarray analyses using 4608 unique clones from liver-derived expressed sequence tag (EST) libraries fortified with clones of known liver genes representing approximately 4000 genes. Several phase I (P4501A1, -1A2) and phase II [e.g., glutathione-S-transferase (GST)-M1, UDP-glucuronosyl transferases (UGT)] genes were persistently induced (3-10-fold) by MC for 15-28 days. The persistent induction of P4501A1 gene expression was confirmed by real time reverse transcriptase polymerase chain reaction (RT-PCR) experiments. MC also elicited a 5-fold persistent augmentation of acute phase genes such as orosomucoid 1 and alpha-1-acid glycoprotein (AGP), and this was accompanied by sustained liver damage and inflammation in the MC-exposed rats. In conclusion, our results strongly suggest that sustained induction of P4501A1 by MC is accompanied by persistent expression of other genes belonging to the Ah gene battery, as well as certain other genes involved in toxic responses. Elucidating the mechanisms of persistent induction of P4501A1 and other genes by MC might lead to a better understanding of the mechanisms of toxicity mediated by PAHs.
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PMID:Effects of 3-methylcholanthrene on gene expression profiling in the rat using cDNA microarray analyses. 1630 Mar 71

Seminal regulatory controls of microbial arsenite [As(III)] oxidation are described in this study. Transposon mutagenesis of Agrobacterium tumefaciens identified genes essential for As(III) oxidation, including those coding for a two-component signal transduction pair. The transposon interrupted a response regulator gene (referred to as aoxR), which encodes an ntrC-like protein and is immediately downstream of a gene (aoxS) encoding a protein with primary structural features found in sensor histidine kinases. The structural genes for As(III) oxidase (aoxAB), a c-type cytochrome (cytc2and molybdopterin biosynthesis (chlE) were downstream of aoxR. The mutant could not be complemented by aoxSR in trans but was complemented by a clone containing aoxS-aoxR-aoxA-aoxB-cytc2 and consistent with reverse transcriptase (RT) PCR experiments, which demonstrated these genes are cotranscribed as an operon. Expression of aoxAB was monitored by RT-PCR and found to be up-regulated by the addition of As(III) to cell cultures. Expression of aoxAB was also controlled in a fashion consistent with quorum sensing in that (i) expression of aoxAB was absent in As(III)-unexposed early-log-phase cells but was observed in As(III)-unexposed, late-log-phase cells and (ii) treating As(III)-unexposed, early-log-phase cells with ethyl acetate extracts of As(III)-unexposed, late-log-phase culture supernatants also resulted in aoxAB induction. Under inducing conditions, aoxS expression was readily observed in the wild-type strain but significantly reduced in the mutant, indicating that AoxR is autoregulatory and at least partially controls the expression of the aox operon. In summary, regulation of A. tumefaciens As(III) oxidation is complex, apparently being controlled by As(III) exposure, a two-component signal transduction system, and quorum sensing.
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PMID:Complex regulation of arsenite oxidation in Agrobacterium tumefaciens. 1642 12

Respirable quartz has been classified as a human lung carcinogen, but the mechanism by which quartz exposure leads to lung cancer has not been clarified. Consistently higher risks of lung cancer are reported in smokers with quartz exposure and we therefore hypothesised that quartz exposure may alter the expression of enzyme systems involved in activation/detoxification of pre-carcinogens in cigarette smoke. More specifically we studied cytochrome P4501A1 (CYP1A1) expression using reverse transcriptase polymerase chain reaction and immunohistochemistry (IHC) upon in vitro and in vivo quartz exposure. In vitro incubation of rat lung epithelial cells with DQ12 quartz for 24 h showed a dose-dependent induction of CYP1A1-mRNA. On the other hand, CYP1A1 message was not increased in lung epithelial cells isolated from rats at 3, 28 or 90 days after intratracheal instillation of 2 mg DQ12. Following IHC for CYP1A1 protein in rat lung sections from later time-points (180 and 360 days), we observed an increase in the number of CYP1A1 positive cells. After in vivo quartz exposure, protein expression of the Aryl hydrocarbon receptor (AhR) was increased and nuclear translocation of AhR was observed at the same time-points. In conclusion, our findings demonstrate an effect of quartz exposure on chronic CYP1A1 expression in vivo, whereas the in vitro models show an immediate upregulation. We suggest that this upregulation of CYP1A1 may act as a co-carcinogenic pathway in quartz exposed workers by activation of pre-carcinogens such as those present in cigarette smoke.
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PMID:Induction of CYP1A1 in rat lung cells following in vivo and in vitro exposure to quartz. 1654 97

Platelet-derived growth factor (PDGF)-BB and PDGF-DD mediate mesangial cell proliferation in vitro and in vivo. While PDGF-BB is a ligand for the PDGF alpha- and beta-receptor chains, PDGF-DD binds more selectively to the beta-chain, suggesting potential differences in the biological activities. Signal transduction and regulation of gene expression induced by PDGF-BB and -DD were compared in primary human mesangial cells (HMCs), which expressed PDGF alpha- and beta-receptor subunits. The growth factor concentrations used were chosen based on their equipotency in inducing HMCs proliferation and binding to the betabeta-receptor. Both growth factors, albeit at different concentrations induced phosphorylation and activation of extracellular signal-regulated kinase 1 (ERK1) and ERK2. In addition, PDGFs led to the phosphorylation and activation of signal transducers and activators of transcription 1 (STAT1) and STAT3. HMCs proliferation induced by either PDGF-BB or -DD could be blocked by signal transduction inhibitors of the mitogen-activated protein kinase-, Janus kinase (JAK)/STAT-, or phosphatidyl-inositol 3-kinase pathways. Using a gene chip array and subsequent verification by real-time reverse transcriptase (RT)-polymerase chain reaction, we found that in HMC genes for matrix metalloproteinase 13 (MMP-13) and MMP-14 and, to a low extent, cytochrome B5 and cathepsin L were exclusively regulated by PDGF-BB, whereas no exclusive gene regulation was detected by PDGF-DD. However, at the protein level, both MMP-13 and -14 were equally induced by PDGF-BB and -DD. PDGF-BB and -DD effect similar biological responses in HMCs albeit at different potencies. Rare apparently differential gene regulation did not result in different protein expression, suggesting that in HMCs both PDGFs exert their biological activity almost exclusively via the PDGF beta-receptor.
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PMID:Biological responses to PDGF-BB versus PDGF-DD in human mesangial cells. 1655 24

It is controversial whether women have a higher lung cancer susceptibility compared to men. We previously reported higher levels of smoking-related bulky DNA adducts in female lungs. In a pilot study (27 cases), we also found a higher level of female lung cytochrome P4501A1 (CYP1A1) gene expression. In the present extended study we report on the pulmonary expression of several genes involved in polycyclic aromatic hydrocarbon bioactivation in relation to sex, smoking and DNA adducts. CYP1A1, CYP1B1, aryl hydrocarbon receptor and microsomal epoxide hydrolase gene expression was measured by quantitative real-time reverse transcriptase-PCR in 121 normal lung tissue samples. The expression of CYP1A1 and CYP1B1 was significantly higher among current smokers compared to ex-smokers and never-smokers. Among current smokers, females had a 3.9-fold higher median level of CYP1A1 compared to males (p = 0.011). CYP1B1 expression was not related to sex. Lung DNA adducts (measured by 32P-postlabeling) were highly significantly related to CYP1A1 (p < 0.0001) irrespective of smoking-status. Our results are consistent with the hypothesis that CYP1A1 plays a significant role in lung DNA adduct formation and support a higher susceptibility to lung cancer among females.
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PMID:Sex differences in risk of lung cancer: Expression of genes in the PAH bioactivation pathway in relation to smoking and bulky DNA adducts. 1655 73

Inducibility of the cytochrome P4501A4 (CYP1A4) enzyme, measured as ethoxyresorufin-O-deethylase (EROD) activity, has been used as a biomarker for sensitivity to the effects of dioxin-like compounds in avian species. Here, we present a quantitative reverse transcriptase-PCR (Q-PCR) method for assessing this biomarker response at the level of messenger RNA (mRNA) expression. The method was validated for use in fresh samples as well as samples that have been analyzed for EROD activity previously. Concentration-dependent effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on CYP1A4 and CYP1A5 mRNA abundance were detected in fresh and post-EROD hepatocyte cultures. Although the quality of the RNA obtained from post-EROD samples was low, quantification of the CYP1A mRNA response to TCDD was not compromised. Several benefits of evaluating CYP1A mRNA expression in addition to EROD activity were noted. The CYP1A mRNA bioassay may provide more accurate estimates for the potency of environmental mixtures of contaminants and has a very low detection limit. When working with hepatocytes cultured from wild or endangered species, our approach can help to circumvent the problem of small sample size by maximizing the amount of data obtained from each sample.
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PMID:Same-sample analysis of ethoxyresorufin-O-deethylase activity and cytochrome P4501A mRNA abundance in chicken embryo hepatocytes. 1713 51

A comprehensive understanding of the mechanisms that underlie hepatic differentiation inside a bioartificial liver (BAL) device is obtained when functional, histological, and gene expression analyses can be combined. We therefore developed a novel cell-sampling technique that enabled us to analyze adherent hepatocytes inside a BAL device during a 5-day culture period, without the necessity of terminating the culture. Biochemical data showed that hepatocyte-specific functions were relatively stable, despite an increase in glycolytic activity. Quantitative reverse transcriptase polymerase chain reaction analysis of hepatic genes cytochrome p450 3A29, albumin, glutamine synthetase, alpha-1 antitrypsin, and carbamoyl-phosphate synthetase, but also de-differentiation marker pi-class glutathione S transferase showed stable messenger ribonucleic acid (mRNA) levels from day 1 to 5. In contrast, mRNA levels of alpha-fetoprotein, pro- and anti-apoptotic genes Bax-alpha and Bcl-X(L), metabolic genes lactate dehydrogenase and uncoupling protein 2, and cytoskeleton genes alpha- and beta-tubulin and beta-actin increased in 5 days. Histological analysis revealed viable tissue-like structures with adaptation to the in vitro environment. We conclude that hepatocytes show a tendency for de-differentiation shortly after seeding but thereafter remain acceptably differentiated during 5 days of culture. Furthermore, partly impaired mitochondrial function is suggestive for local hypoxic regions and may trigger the observed metabolic changes. Anti-apoptotic activity seems to balance pro-apoptotic activity. This new cell-sampling technique facilitates the analysis of dynamic processes of hepatocyte culture inside a BAL.
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PMID:Time-related analysis of metabolic liver functions, cellular morphology, and gene expression of hepatocytes cultured in the bioartificial liver of the Academic Medical Center in Amsterdam (AMC-BAL). 1751 23

Stenoxybacter acetivorans is a newly described, obligately microaerophilic beta-proteobacterium that is abundant in the acetate-rich hindgut of Reticulitermes. Here we tested the hypotheses that cells are located in the hypoxic, peripheral region of Reticulitermes flavipes hindguts and use acetate to fuel their O(2)-consuming respiratory activity in situ. Physical fractionation of R. flavipes guts, followed by limited-cycle PCR with S. acetivorans-specific 16S rRNA gene primers, indicated that cells of this organism were indeed located primarily among the microbiota colonizing the hindgut wall. Likewise, reverse transcriptase PCR of hindgut RNA revealed S. acetivorans-specific transcripts for acetate-activating enzymes that were also found in cell extracts (acetate kinase and phosphotransacetylase), as well as transcripts of ccoN, which encodes the O(2)-reducing subunit of high-affinity cbb(3)-type cytochrome oxidases. However, S. acetivorans strains did not possess typical enzymes of the glyoxylate cycle (isocitrate lyase and malate synthase A), suggesting that they may use an alternate pathway to replenish tricarboxylic acid cycle intermediates or they obtain such compounds (or their precursors) in situ. Respirometric measurements indicated that much of the O(2) consumption by R. flavipes worker larvae was attributable to their guts, and the potential contribution of S. acetivorans to O(2) consumption by extracted guts was about 0.2%, a value similar to that obtained for other hindgut bacteria examined. Similar measurements obtained with guts of larvae prefed diets to disrupt major members of the hindgut microbiota implied that most of the O(2) consumption observed with extracted guts was attributable to protozoans, a group of microbes long thought to be "strict anaerobes."
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PMID:Physiological ecology of Stenoxybacter acetivorans, an obligate microaerophile in termite guts. 1782 35

1. Ginkgo biloba is one of the most popular herbal medicines worldwide due to its memory-enhancing and cognition-improving effects. The current study was designed to investigate the effects of five major constituents (bilobalide, ginkgolide A, B, quercetin, and kaempferol) in the standardized G. biloba extract EGb 761 on various cytochrome P450s (CYPs) in rats. 2. The activity of CYP450 was measured by the quantification of six metabolites from multiple cytochrome P450 probe substrates using a validated liquid chromatography coupled with tandem mass spectrometry detection (LC-MS/MS) method. The levels of messenger RNA (mRNA) and protein of various CYPs were determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting analysis, respectively. 3. Bilobalide significantly induced the activity, protein, and mRNA expression of CYP3A1 and 1A2, and increased CYP2E1 activity and CYP2B1/2 protein expression in a dose-dependent manner. 4. Ginkgolide A, B, quercetin, and kaempferol did not affect CYP3A1, but induced CYP1A2 in a dose-dependent manner. EGb 761 and the five individual constituents had no effects on rat CYP2D2, 2C11 and 2C7. 5. The results indicate that bilobalide, and to a lesser extent ginkgolide A, B, quercetin, and kaempferol, play a key role in the effects of EGb 761 on CYP induction. Further study is needed to elucidate the mechanism of CYP3A induction by EGb 761 and bilobalide.
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PMID:Induction of cytochrome P450s by terpene trilactones and flavonoids of the Ginkgo biloba extract EGb 761 in rats. 1842 21


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