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)

Gastrin, a potent stimulator of gastric acid secretion, primarily targets the acid-secreting parietal cells and histamine-secreting enterochromaffin-like (ECL) cells in the stomach. Accordingly, gastrin-deficient (GAS-KO) mice have a severe impairment in acid secretion. The aim of this study was to characterize changes in gene expression in GAS-KO mice to identify gastrin-regulated genes and to gain insight into how gastric cell types are regulated by gastrin and acid secretion. Affymetrix microarray analysis of GAS-KO and wild-type mice identified numerous differentially expressed transcripts. The results were compared with GAS-KO mice treated with gastrin to identify genes that were gastrin responsive. Finally, genes that were primarily changed due to gastrin and not hypochlorhydria were identified by comparison to mice that are deficient in both gastrin and cholecystokinin (GAS/CCK-KO), since these mice have restored basal acid secretion. The data were validated by quantitative reverse transcriptase polymerase chain reaction analysis. Interestingly, a number of inflammatory response genes were induced in GAS-KO mice and normalized in GAS/CCK-KO mice, suggesting that they were increased in response to low gastric acid. Moreover, a number of parietal cell transcripts that were downregulated in GAS-KO mice were similarly restored in GAS/CCK-KO mice, suggesting that parietal cell changes were also primarily associated with hypochlorhydria. In contrast, ECL cell genes that were markedly downregulated in GAS-KO mice continued to be reduced in GAS/CCK-KO mice, demonstrating that gastrin coordinately regulates a number of ECL cell genes, including several involved in histamine synthesis and secretion.
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PMID:Transcriptional profiling of gastrin-regulated genes in mouse stomach. 1710 52

Gastrin isoforms, acting through a variety of receptors, have proliferative and anti-apoptotic effects on gastrointestinal (GI) cancers. A small interfering RNA (siRNA) targeting the gastrin gene was used to investigate the role of endogenous gastrin in GI cancer cell survival. Downregulation of the gastrin gene in siRNA-transfected cells was measured using real-time reverse transcriptase-PCR. The most effective siRNA was tested in a panel of GI cancer cell lines at various concentrations and time points, and the effect on cell survival and apoptosis was measured using methyl thiazoyl tetrazolium (MTT) and caspase 3 activation assays. Gastrin siRNA reduced gene expression by more than 90% in a range of GI cancer cell lines. Downregulation of the gastrin gene was dose-dependent and effective over approximately 1 week in vitro. However, downregulation at the protein level was delayed by 3-4 days. Gastrin siRNA-transfected cells showed up to a 60% reduction in growth and up to a 50% increase in apoptosis compared with control siRNA-transfected cells. The effects were most marked in the cell line with the highest constitutive level of gastrin gene expression (human metastatic colon, C170HM2) and in epidermal growth factor (EGF)-treated cells as the gastrin promoter contains an EGF-response element, gERE. The ability of the siRNAs to reduce survival of these GI cell lines is further evidence of the importance of autocrine and/or intracrine gastrin loops in GI cancer, where expression of the gastrin gene and autonomous gastrin appears widespread.
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PMID:Use of interfering RNA to investigate the role of endogenous gastrin in the survival of gastrointestinal cancer cells. 1726 81

Proteinase-activated receptor-2 (PAR-2) belongs to a novel subfamily of G protein-coupled receptors with seven-transmembrane domains. PAR-2 is activated by serine proteases, such as trypsin, mast cell tryptase, and allergic or bacterial proteases. The presence of trypsin has been shown in human stomach. Cyclooxygenase-2 (COX-2) is induced by inflammatory cytokines, growth factors, gastrin, and reactive oxygen species in gastric epithelial cells, which may lead to mutagenesis and subsequent metaplasia, dysplasia, and cancer formation. We investigated whether PAR-2 is activated in H. pylori (HP99)-infected cells, which is related to COX-2 induction in gastric epithelial cells. After treatment of H. pylori to AGS (gastric adenocarcinoma) cells at a bacteria/cell ratio of 100:1, we determine the expression and the activation of PAR-2 and the expression of COX-2. The same experiments were performed in the cells treated with PAR-2 agonist peptide. mRNA and protein expression of PAR-2 and COX-2 were determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. PAR-2 activation was assessed by increase in intracellular calcium level. As a result, H. pylori induced the activation and expression of PAR-2 as well as COX-2 expression. PAR-2 agonist peptide augmented H. pylori-induced COX-2 expression in AGS cells. H. pylori induces COX-2 expression, which is mediated by both activation and expression of PAR-2 in gastric epithelial cells.
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PMID:Role of proteinase-activated receptor-2 on cyclooxygenase-2 expression in H. pylori-infected gastric epithelial cells. 1740 13

Gastric enterochromaffin-like (ECL) cells release histamine in response to food because of elevation of gastrin and neural release of pituitary adenylate cyclase-activating peptide (PACAP). Acid secretion is at a basal level in the absence of food but is rapidly stimulated with feeding. Rats fasted for 24 h showed a significant decrease of mucosal histamine despite steady-state expression of the histamine-synthesizing enzyme histidine decarboxylase (HDC). Comparative transcriptomal analysis using gene expression oligonucleotide microarrays of 95% pure ECL cells from fed and 24-h fasted rats, thereby eliminating mRNA contamination from other gastric mucosal cell types, identified significantly increased gene expression of the enzymes histidase and urocanase catabolizing the HDC substrate L-histidine but significantly decreased expression of the cellular L-histidine uptake transporter SN2 and of the vesicular monoamine transporter 2 (VMAT-2) responsible for histamine uptake into secretory vesicles. This was confirmed by reverse transcriptase-quantitative polymerase chain reaction of gastric fundic mucosal samples from fed and 24-h fasted rats. The decrease of VMAT-2 gene expression was also shown by a decrease in VMAT-2 protein content in protein extracts from fed and 24-h fasted rats compared with equal amounts of HDC protein and Na-K-ATPase alpha(1)-subunit protein content. These results indicate that rat gastric ECL cells regulate their histamine content during 24-h fasting not by a change in HDC gene or protein expression but by regulation of substrate concentration for HDC and a decreased histamine secretory pool.
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PMID:Fasting-induced changes in ECL cell gene expression. 1753 21

INTRODUCTION:: The aim of this study was to investigate whether combined epidermal growth factor (EGF) and gastrin can correct the hyperglycemia induced by streptozotocin (STZ) in rats and to determine the involvement of the transcription factor pancreatic and duodenal homeobox 1 (PDX1) in this process. METHODS:: Rat diabetes was induced by intraperitoneal injection of STZ. The mRNA and protein levels of insulin and PDX1 were determined by real-time reverse transcriptase polymerase chain reaction and immunohistochemistry. Serum levels of C-peptide and insulin were analyzed using radioimmunoassay kits. RESULTS:: The combined administration of EGF and gastrin efficiently reversed the hyperglycemia induced by STZ. Elevated insulin concentration was detected in diabetic rats treated with EGF plus gastrin. The authors also found that both insulin and PDX1 expression were reduced in STZ-treated rats. Interestingly, the combination treatment also significantly enhanced the mRNA levels of insulin and PDX1, and that of their protein products. CONCLUSIONS:: Therapy with EGF plus gastrin corrected hyperglycemia and maintained insulin content in STZ-induced diabetic rats via up-regulation of PDX1 expression, suggesting that this combination treatment may provide a valuable approach for pancreatic islet neogenesis in vivo.
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PMID:Effects of Combined Epidermal Growth Factor and Gastrin on PDX1 Expression in Experimental Type 1 Diabetic Rats. 2180 73

The means of identifying prostate carcinoma and its metastases are limited. The contrast agents used in magnetic resonance imaging clinical diagnostics are not taken up into the tumor cells, but only accumulate in the interstitial space of the highly vasculated tumor. We examined the gastrin/cholecystokinin-B receptor as a possible target for prostate-specific detection using the C-terminal seven amino acid sequence of the gastrin peptide hormone. The correct sequence and a scrambled control sequence were coupled to the fluorescent dye rhodamine and the magnetic resonance imaging contrast agent gadolinium (Gd)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). Expression analysis of the gastrin receptor mRNA was performed by reverse transcriptase polymerase chain reaction on PC3 prostate carcinoma cells, U373 glioma, U2OS osteosarcoma and Colo205 colon carcinoma cells. After having confirmed elevated expression of gastrin receptor in PC3 cells and very low expression of the receptor in Colo205 cells, these two cell lines were used to create tumor xenografts on nude mice for in vivo experiments. Confocal lasers scanning microscopy and magnetic resonance imaging showed a high specificity of the correct conjugate for the PC3 xenografts. Staining of the PC3 xenografts was much weaker with the scrambled conjugate while the Colo205 xenografts showed no marked staining with any of the conjugates. In vitro experiments comparing the correct and scrambled conjugates on PC3 cells by magnetic resonance relaxometry and fluorescence-activated cell sorting confirmed markedly higher specificity of the correct conjugate. The investigations show that the gastrin receptor is a promising tumor cell surface target for future prostate-cancer-specific imaging applications.
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PMID:The gastrin/cholecystokinin-B receptor on prostate cells--a novel target for bifunctional prostate cancer imaging. 2421 50


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