Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.26.9 (ribonuclease)
 6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A cDNA clone of prostaglandin (PG) E receptor EP1 subtype (rEP1) was isolated from a rat uterus cDNA library. It encodes 405 amino acid residues with seven transmembrane-spanning domains and couples to Ca2+ mobilization. In addition, three cDNA clones encoding a variant form of rEP1 were isolated. The open reading frame can code a 366-amino acid protein carrying a specific change of 49 amino acids from the middle of transmembrane segment VI to COOH terminus; it possesses a transmembrane segment VII-like structure lacking an intracellular COOH-terminal tail. Southern blot analysis of rat genomic DNA and genomic polymerase chain reaction demonstrated that these cDNAs were derived from a single copy gene. Northern blot analysis and ribonuclease protection assay revealed that both rEP1 and rEP1-variant receptor mRNAs were highly expressed in the kidney. Immunoblot with an antibody directed toward the specific region of rEP1-variant receptor showed that rEP1-variant receptor protein was expressed in the membrane of the kidney and Chinese hamster ovary (CHO) cells transfected with rEP1-variant cDNA. Thus, the rEP1-variant receptor is translated from mRNA which is not spliced at nucleotide position 952 in the segment VI transmembrane region. rEP1-variant receptor retained the ligand binding activity with affinity and specificity similar to rEP1 receptor, but lost the coupling of signal transduction systems by itself. However, when rEP1-variant receptor was stably co-expressed with rEP1 receptor in CHO cells, the Ca2+ mobilization mediated by EP1 receptor was significantly suppressed. Furthermore, when rEP1-variant receptor was expressed in CHO cells, cAMP formation by activation of endogenous EP4 receptor was strongly blocked. These results suggest that the rEP1-variant receptor may affect the efficiency of signal coupling of PGE receptors and attenuate the action of PGE2 on tissues.
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PMID:Suppression of prostaglandin E receptor signaling by the variant form of EP1 subtype. 894 Jan 29

We examined the potential of several epithelial-derived factors to enhance neutrophil activation and survival. Neutrophils incubated in the presence of supernatants from nasal-derived primary epithelial cultures had significantly increased survival compared with neutrophils cultured in media alone. Of the cytokines reported to enhance neutrophil survival, transcripts for interleukin (IL)-1alpha, IL-1beta, IL-6, and granulocyte macrophage colony-stimulating factor (GM-CSF) (but not interferon-gamma or granulocyte colony-stimulating factor [G-CSF]) were detected by ribonuclease protection assay in basal and tumor necrosis factor (TNF)-alpha- stimulated epithelial cells. Of the eicosanoid products that enhance neutrophil survival, platelet-activating factor and leukotriene B(4) were not detected in the supernatants, whereas prostaglandin E(2) (PGE(2)) was produced in modest amounts. The levels of IL-6, GM-CSF, and PGE(2) in epithelial supernatants were significantly increased after transient TNF-alpha stimulation. This induction was suppressed if dexamethasone (Dex) was added during TNF-alpha stimulation. Only IL-6, GM-CSF, and PGE(2) promoted neutrophil survival over the range of concentrations detected in the supernatants, and a combination of neutralizing antibodies to GM-CSF and IL-6 completely inhibited the enhanced neutrophil survival in epithelial supernatants. Both the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling technique and morphologic scoring of apoptotic neutrophils confirmed that epithelial supernatants, as well as purified IL-6, GM-CSF, and PGE(2) all delayed neutrophil apoptosis. Finally, the effects of Dex on neutrophil survival and on epithelial cytokine production were investigated. Dex independently prolonged neutrophil survival but suppressed epithelial production of survival-enhancing factors in a dose-dependent manner. The net effect of Dex appeared to favor neutrophil survival.
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PMID:Multiple epithelial cell-derived factors enhance neutrophil survival. Regulation by glucocorticoids and tumor necrosis factor-alpha. 1042 10

Although 3':5' cyclic adenosine monophosphate (cAMP) is known to modulate cytokine production in a number of cell types, little information exists regarding cAMP-mediated effects on this synthetic function of human airway smooth-muscle (HASM) cells. We examined the effect of increasing intracellular cAMP concentration ([cAMP](i)) on tumor necrosis factor (TNF)-alpha-induced regulated on activation, normal T cells expressed and secreted (RANTES) and interleukin (IL)-6 secretion from cultured HASM cells. Pretreatment of HASM with prostaglandin (PG) E(2), forskolin, or dibutyryl cAMP inhibited TNF-alpha-induced RANTES secretion but increased TNF-alpha-induced IL-6 secretion. Moreover, stimulation with PGE(2), forskolin, or dibutyryl cAMP alone increased basal IL-6 secretion in a concentration-dependent manner. SB 207499, a specific phosphodiesterase type 4 inhibitor, augmented the inhibitory effects of PGE(2) and forskolin on TNF-alpha-induced RANTES. Collectively, these data demonstrate that increasing [cAMP](i) in HASM effectively increases IL-6 secretion but reduces RANTES secretion promoted by TNF-alpha. Reverse transcriptase/polymerase chain reaction and ribonuclease protection assays suggested that these opposite effects of increased [cAMP](i) on TNF-alpha- induced IL-6 and RANTES secretion may occur at the transcriptional level. Accordingly, we examined the effects of TNF- alpha and cAMP on the regulation of nuclear factor (NF)-kappaB, a transcription factor known to modulate cytokine synthesis in numerous cell types. Stimulation of HASM cells with TNF-alpha increased NF-kappaB DNA-binding activity. However, increased [cAMP](i) in HASM neither activated NF-kappaB nor altered TNF-alpha- induced NF-kappaB DNA-binding activity. These results were confirmed using a NF-kappaB-luciferase reporter assay. Together, our data suggest that TNF-alpha-induced IL-6 and RANTES secretion may be associated with NF-kappaB activation, and that inhibition of TNF-alpha-stimulated RANTES secretion and augmentation of IL-6 secretion by increased [cAMP](i) in HASM cells occurs via an NF-kappaB-independent mechanism.
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PMID:Tumor necrosis factor-alpha-induced secretion of RANTES and interleukin-6 from human airway smooth-muscle cells. Modulation by cyclic adenosine monophosphate. 1110 33

This study was designed to investigate the possible role of cyclo-oxygenase-2 (COX-2) and prostaglandin E(2)(PGE(2)) in endometrial adenocarcinoma. COX-2 RNA expression was confirmed in various grades of adenocarcinoma by ribonuclease protection assay. COX-2 and microsomal glutathione-dependent prostaglandin E synthase (mPGES) expression and PGE(2)synthesis were localised to the neoplastic epithelial cells and endothelial cells. In order to establish whether PGE(2)has an autocrine/paracrine effect in adenocarcinomas, we investigated the expression of 2 subtypes of PGE(2)receptors, namely EP2 and EP4, by real time quantitative PCR. Expression of EP2 and EP4 receptors was detected in adenocarcinomas from all grades of differentiation and was significantly higher than that detected in normal secretory phase endometrium (P< 0.01). The fold induction of expression in adenocarcinoma compared with normal secretory phase endometrium was 28.0 +/- 7.4 and 52.5 +/- 10.1 for EP2 and EP4 receptors respectively. Immunohistochemistry localised the site of expression of EP4 receptor in neoplastic epithelial cells and in the endothelium of carcinomas of all grades of differentiation. Finally, the functionality of the EP2/EP4 receptors was assessed by investigating cAMP generation following in vitro culture of adenocarcinoma tissue in the presence or absence of 300 nM PGE(2). cAMP production in response to PGE(2)was significantly higher in carcinoma tissue than that detected in normal secretory phase endometrium (3.42 +/- 0.46 vs 1.15 +/- 0.05 respectively; P< 0.001). In conclusion, these data suggest that PGE(2)may regulate neoplastic cell function in an autocrine/paracrine manner via the EP2/EP4 receptors.
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PMID:Expression of COX-2 and PGE synthase and synthesis of PGE(2)in endometrial adenocarcinoma: a possible autocrine/paracrine regulation of neoplastic cell function via EP2/EP4 receptors. 1159 75