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)

We investigated the role of nitric oxide (NO)-guanosine 3',5'-cyclic monophosphate (cGMP) signaling in the regulation of rabbit clitoral cavernosum (CC) tone. Tension measurements, reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting, and NADPH-diaphorase staining were performed in CC. In the precontracted CC strips with phenylephrine (10(-5) M), acetylcholine (ACh) relaxed, dependent on dosage. Pretreatment with atropine, N(omega) nitro-L-arginine-methyl ester (NAME) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), guanylate cyclase inhibitor abolished the ACh-induced relaxations, but tetrodotoxin (TTX) did not. Sodium nitroprusside relaxed the strips in the presence of atropine and NAME, but not in the presence of ODQ. Electrical field stimulation (EFS) relaxed the strips dependent on stimulus strength. Pretreatment with TTX, NAME, or ODQ abolished the EFS-induced relaxation, but atropine did not. L-Arginine partially restored the inhibited response to ACh and EFS. The inducible NO synthase (iNOS) and neuronal NOS (nNOS) mRNAs and iNOS and endothelial NOS (eNOS) proteins were identified in the CC. NADPH-diaphorase staining revealed the positivity on the nerve trunks and fine nerve fibers in the CC. Finally, results demonstrate that the nNOS, ENOS, and the NO-cGMP signaling pathway are involved in the regulation of clitoral tumescence.
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PMID:Nitric oxide-cyclic GMP signaling pathway in the regulation of rabbit clitoral cavernosum tone. 1248 13

To investigate the expression of the HO-1 gene in PC12 cells in hypoxic environment and gain further insight to the role of HO-1 in cerebral ischemia, PC12 cells were exposed to hypoxia environment (95% N2, 5% CO2) for 0.5 h, 1 h, 4 h, 8 h, 12 h, 24 h respectively. The level of HO-1 mRNA was examined by reverse transcriptase polymerase chain reaction (RT-PCR); the volume of COHb in the media were measured spectrophotometrically and the cGMP concentration of PC12 cell extracts was determined by radioimmunoassay. We found that after exposure to hypoxia for 1 h, 4 h, 8 h, 12 h, 24 h, HO-1 mRNA increased by 3%, 4%, 17%, 31% 36% as compared with that in control group respectively (P < 0.01 or P < 0.05); the COHb increased by 12%, 29%, 59%, 88%, 94% as compared with that in control group respectively (P < 0.01 or P < 0.05), and the cGMP concentration were 2.2, 3.4, 5.2, 8.1, 10.9-fold as that of the control group (P < 0.01). We are led to conclude that hypoxia induced the expression of HO-1 gene, the production of endogenous CO, and the concentration of cGMP was elevated as well.
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PMID:Induction of the expression of heme oxygenase gene in PC12 cells by hypoxia. 1267 63

Exposure to chronic hypoxia (CH) induces a sustained pulmonary hypertension associated with structural and functional changes in the pulmonary arterial bed, including alterations of contractile properties. The small G-protein RhoA and its effector Rho kinase play a major role in the sustained rise in tension induced by vasoconstrictors. The aim of this study was to analyze the effect of CH on the RhoA/Rho kinase signaling pathway in the rat pulmonary artery. Maximal contraction of pulmonary artery rings to endothelin-1, noradrenaline, and the thromboxane A2 analog U46619 was markedly decreased in rats exposed to CH (10% O2, 2 weeks). This CH-induced decrease response to agonists was attributable to the abolition of RhoA-mediated Ca2+ sensitization of the contraction. Real-time reverse transcriptase-polymerase chain reaction and Western blot analysis revealed a decrease in RhoA mRNA (79.4+/-6.0%, n=4) and RhoA (81.1+/-8.0%, n=4) expression in the main pulmonary artery from CH rats, whereas RhoA expression was not modified in arterial smooth muscle cells and arteries exposed to hypoxia and high intraluminal pressure, respectively. Treatment of rats with sildenafil (25 mg/kg per day) throughout 2 weeks of exposure to CH prevented CH-induced downregulation of RhoA, reduction of contraction, and pulmonary artery remodeling. These findings indicate that CH-induced downregulation of RhoA expression, leading to the abolition of RhoA/Rho kinase-mediated Ca2+ sensitization of contraction, is responsible for the decreased responses to contracting agonists in the pulmonary artery of CH rats. These alterations are prevented by sildenafil, indicating a major role of the NO/cyclic GMP pathway in CH-induced altered RhoA signaling in the pulmonary artery.
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PMID:Sildenafil prevents change in RhoA expression induced by chronic hypoxia in rat pulmonary artery. 1294 46

The cannabinoid analog "abnormal cannabidiol" (abn-cbd) causes endothelium-dependent vasodilation in rat isolated mesenteric arteries through a G protein-coupled receptor distinct from CB1 or CB2. We examined the actions of abn-cbd on the electrophysiology of human umbilical vein endothelial cells (HUVEC), using the whole cell version of the patch clamp technique. Voltage steps produced noninactivating outward currents, which were abolished by iberiotoxin or by chelation of intracellular calcium. The presence of a BKCa channel in HUVEC was documented by reverse transcriptase-PCR. Abn-cbd concentration dependently potentiated the outward current produced by a single voltage step. This potentiation was abolished by the cannabidiol analog O-1918 or by pertussis toxin but was unaffected by CB1 or CB2 antagonists. HU-210, a CB1/CB2 receptor agonist, had no effect on the outward current. Clamping [Ca2+]i did not prevent abn-cbd-induced increases in outward current. cGMP potentiated the outward current, and abn-cbd increased the cellular levels of cGMP. The increase in outward current produced by abn-cbd was blocked by KT-5823, an inhibitor of protein kinase G, or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ), an inhibitor of soluble guanylate cyclase. We conclude that a Ca2+-activated K+ current in HUVEC is potentiated by activation of a Gi/Go-coupled receptor distinct from CB1 or CB2, which signals through cGMP and protein kinase G to increase channel availability or the sensitivity of the channel to voltage and/or Ca2+. Because iberiotoxin also inhibited abn-cbd-induced relaxation of intact, but not of endothelium-denuded, rat mesenteric artery segments, modulation of endothelial BKCa channels may underlie the mesenteric vasodilator action of abn-cbd.
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PMID:G protein-coupled endothelial receptor for atypical cannabinoid ligands modulates a Ca2+-dependent K+ current. 1295 47

To examine the possible role of the bradykinin-NO system in the action of ACE inhibitors, we studied the effects of imidapril, an ACE inhibitor, on inflammatory vascular injury by using AT1a-receptor-deficient (AT1aKO) mice. A polyethylene cuff was placed around the femoral artery of AT1aKO mice and wild-type (WT; C57BL/6J) mice. Neointimal area in cross sections of the artery was measured 14 days after cuff placement. A low dose of imidapril (1 mg/kg per day), which did not affect blood pressure, was administered by gavage. Expression of monocyte chemoattractant protein (MCP)-1 and tumor necrosis factor (TNF)-alpha was detected by immunohistochemical staining and reverse transcriptase-polymerase chain reaction (RT-PCR) 7 days after the operation. Neointimal formation, vascular smooth muscle cell proliferation, and expression of MCP-1 and TNF-alpha were attenuated in the injured artery in AT1aKO mice compared with those in WT mice. Imidapril inhibited neointimal formation, DNA synthesis of vascular smooth muscle cells, and expression of MCP-1 and TNF-alpha in AT1aKO mice as well as in WT mice. In addition, imidapril increased tissue cGMP content after cuff placement. These inhibitory effects of imidapril were significantly reduced or abolished by a bradykinin receptor antagonist, Hoechst 140, or an NO synthase inhibitor, L-NAME, both in WT and AT1aKO mice. Treatment with imidapril did not change AT2 receptor and ACE expression detected by RT-PCR in the injured artery. These results indicate that not only blockade of angiotensin II production but also activation of the bradykinin-NO system plays an important role in the beneficial effects of imidapril on vascular remodeling.
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PMID:Important role of nitric oxide in the effect of angiotensin-converting enzyme inhibitor imidapril on vascular injury. 1296 79

We have identified a novel membrane form of guanylate cyclase (GC) from a mouse testis cDNA library and termed it mGC-G (mouse GC-G) based on its high sequence homology to rat GC-G. It encodes a potential type I transmembrane receptor, with the characteristic domain structure common to all members of the family of membrane GCs, including an extracellular, putative ligand-binding domain, a single membrane-spanning segment and cytoplasmic protein kinase-like and cyclase catalytic domains. Real-time quantitative reverse transcriptase--PCR and Northern-blot analyses showed that mGC-G is highly and selectively expressed in mouse testis. Phylogenetic analysis based on the extracellular protein sequence revealed that mGC-G is closely related to members of the subfamily of natriuretic peptide receptor GCs. When overexpressed in HEK-293T cells (human embryonic kidney 293T cells) or COS-7 cells, mGC-G manifests as a membrane-bound glycoprotein, which can form either homomeric or heteromeric complexes with the natriuretic peptide receptor GC-A. It exhibits marked cGMP-generating GC activity; however, notably, all ligands known to activate other receptor GCs failed to stimulate enzymic activity. The unique testis-enriched expression of mGC-G, which is completely different from the broader tissue distribution of rat GC-G, suggests the existence of as-yet-unidentified ligands and unappreciated species-specific physiological functions mediated through mGC-G/cGMP signalling in the testis.
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PMID:Identification of an orphan guanylate cyclase receptor selectively expressed in mouse testis. 1471 86

We employed differential display of expressed mRNAs (Liang, P., and Pardee, A. B. (1992) Science 257, 967-971) to identify genes up-regulated after long term potentiation (LTP) induction in the hippocampus of awake adult rats. In situ hybridization confirmed the differential expression of five independently amplified clones representing two distinct transcripts, cl13/19/90 and cl95/96. Neither cl13/19/90 nor cl95/96 showed significant sequence homology to known transcripts (mRNA or expressed sequence tag) or to the mouse or human genome. However, comparison with the rat genome revealed that they are localized to a predicted intron of the phosphodiesterase Pde10A gene. cl13/19/90 and cl95/96 are likely to be part of the Pde10A primary transcript as, using reverse transcriptase-PCR, we could specifically amplify distinct introns of the Pde10A primary transcript, and in situ hybridization demonstrated that a subset of Pde10A splice variants are also up-regulated after LTP induction. These results indicate that amplification of a primary transcript can faithfully report gene activity and that differential display can be used to identify differential expression of RNA species other than mRNA. In transiently transfected Cos7 cells, Pde10A3 reduces the atrial natriuretic peptide-induced elevation in cGMP levels without affecting basal cGMP levels. This cellular function of LTP-associated Pde10A transcripts argues for a role of the cGMP/cGMP-dependent kinase pathway in long term synaptic plasticity.
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PMID:Differential amplification of intron-containing transcripts reveals long term potentiation-associated up-regulation of specific Pde10A phosphodiesterase splice variants. 1475 15

Hyperpolarization-activated cation channels of the HCN gene family are crucial for the regulation of cell excitability. Importantly, these channels play a pivotal role in the control of cardiac and neuronal pacemaker activity. Dysfunction of HCN channels has been associated with human diseases, including cardiac arrhythmia, epilepsy, and neuropathic pain. The properties of three HCN channel isoforms (HCN1, HCN2, and HCN4) have been extensively investigated. By contrast, due to the lack of an efficient heterologous expression system, the functional characteristics of HCN3 were by and large unknown so far. Here, we have used lentiviral gene transfer to overexpress HCN3 in HEK293T cells. HCN3 currents revealed slow activation and deactivation kinetics and were effectively blocked by extracellular Cs+ and the bradycardic agent ivabradine. Cyclic AMP and cGMP had no significant impact on activation kinetics but induced a 5-mV shift of the half-maximal activation voltage (V0.5) to more hyperpolarized potentials. A negative shift of V0.5 induced by cyclic nucleotides is an unprecedented feature within the HCN channel family. The expression of HCN3 in mouse brain was examined by Western blot analysis using a specific antibody. High levels of protein were detected in olfactory bulb and hypothalamus. In contrast, only very low expression was found in cortex. Using reverse transcriptase PCR transcripts of HCN3 were also detected in heart ventricle. In conclusion, the distinct expression pattern in conjunction with the unusual biophysical properties implies that HCN3 may play an unique role in the body.
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PMID:The murine HCN3 gene encodes a hyperpolarization-activated cation channel with slow kinetics and unique response to cyclic nucleotides. 1592 85

Cyclic nucleotides cAMP and cGMP are ubiquitous signaling molecules that mediate many adaptative responses in eukaryotic cells. Cyanobacteria present the peculiarity among the prokaryotes of having the two types of cyclic nucleotide. Cellular homeostasis requires both cyclases (adenylyl/guanylyl, for their synthesis) and phosphodiesterases (for their degradation). Fully segregated null mutants have been obtained for the two genes, sll1624 and slr2100, which encode putative cNMP phosphodiesterases. We present physiological evidence that the Synechocystis PCC 6803 open reading frame slr2100 could be a cGMP phosphodiesterase. In addition, we show that Slr2100, but not Sll1624, is required for the adaptation of the cells to a UV-B stress. UV-B radiation has deleterious effects for photosynthetic organisms, in particular on the photosystem II, through damaging the protein structure of the reaction center. Using biophysical and biochemical approaches, it was found that Slr2100 is involved in the signal transduction events which permit the repair of the UV-B-damaged photosystem II. This was confirmed by quantitative reverse transcriptase-PCR analyses. Altogether, the data point to an important role for cGMP in signal transduction and photoacclimation processes during a UV-B stress.
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PMID:Cyclic nucleotides, the photosynthetic apparatus and response to a UV-B stress in the Cyanobacterium Synechocystis sp. PCC 6803. 1609 78

The cystic fibrosis transmembrane conductance regulator (CFTR) is one of the most intensively investigated Cl- channels. Different mutations in the CFTR gene cause the disease cystic fibrosis (CF). CFTR is expressed in the apical membrane of various epithelial cells including the intestine. The major organ affected in CF patients is the lung, but it also causes an important dysfunction of intestinal ion transport. The modulation of CFTR mRNA expression by atrial natriuretic peptide (ANP) was investigated in rat proximal colon and in human intestinal CaCo-2 cells by RNase protection assay and semi-quantitative reverse transcriptase PCR techniques. Groups of rats subjected to volume expansion or intravenous infusion of synthetic ANP showed respective increases of 60 and 50% of CFTR mRNA expression in proximal colon. CFTR mRNA was also increased in cells treated with ANP, reaching a maximum effect at 10(-9) M ANP, probably via cGMP. ANP at 10(-9) M was also able to stimulate both the CFTR promoter region (by luciferase assay) and protein expression in CaCo-2 cells (by Western blot and immunoprecipitation/phosphorylation). These results suggested the involvement of ANP, a hormone involved with extracellular volume, in the expression of CFTR in rat proximal colon and CaCo-2 intestinal cells.
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PMID:Atrial natriuretic peptide modulates cystic fibrosis transmembrane conductance regulator chloride channel expression in rat proximal colon and human intestinal epithelial cells. 1661 90


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