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)

Nitric oxide (NO) promoted the differentiation of clonal stromal cells (ST2 cells) derived from mouse bone marrow to osteoblast-like cells. The level of expression of mRNA for osteocalcin, a marker of osteoblastic differentiation, and the formation of mineralized nodules, increased in ST2 cells treated with a donor of NO. We used the reverse transcriptase-polymerase chain reaction (RT-PCR) to identify the subtypes of NO synthase that were expressed in the ST2 cells and we detected the expression of an inducible NO synthase gene in response to tumor necrosis factor-alpha (TNF-alpha). In various types of cell, NO induces the synthesis of prostaglandin E(2) and cGMP, which are known as regulators of osteoblastic differentiation, by activating cyclooxygenases and soluble guanylate cyclase, respectively. Prostaglandin E(2) was generated in response to NO in ST2 cells, however, no synthesis of cGMP in response to NO was detected. Two inhibitors of cyclooxygenase-2, N-[4-nitro-2-phenoxyphenyl]-methanesulfonamide (nimesulide) and 1-(4-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetic acid (indomethacin), inhibited the formation of mineralized nodules by ST2 cells. Our observations suggest that NO might promote osteoblastic differentiation of ST2 cells by stimulating the production of prostaglandin E(2).
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PMID:Nitric oxide accelerates the ascorbic acid-induced osteoblastic differentiation of mouse stromal ST2 cells by stimulating the production of prostaglandin E(2). 1072 62

Calcium agonists induce membrane depolarization in endothelial cells through an unknown mechanism. Present studies tested the hypothesis that pulmonary artery endothelial cells express a cyclic nucleotide-gated (CNG) cation channel activated by store-operated calcium entry to produce membrane depolarization. In the whole-cell configuration, voltage-clamped cells revealed a large non-inactivating, outwardly rectifying cationic current in the absence of extra- or intracellular Ca(2+) that was reduced upon replenishment of Ca(2+). The inward current was non-selective for K(+), Na(+), Cs(+), and Rb(+) and was not inhibited by high tetraethylammonium concentrations. cAMP and cGMP stimulated the current and changed the cation permeability to favor Na(+). Moreover, 8-bromo-cAMP stimulated the current in voltage-clamped cells in the perforated patch mode. The cationic current was inhibited by the CNG channel blocker LY83,583, and reverse transcriptase-polymerase chain reaction cloning identified expression of a CNG channel resembling that seen in olfactory neurons. Activation of store-operated calcium entry using thapsigargin increased a current through the CNG channel. Stimulation of the current paralleled pulmonary artery endothelial cell membrane depolarization, and both the current and membrane depolarization were abolished using LY83,583. Taken together, these data demonstrate activation of store-operated calcium entry stimulates a CNG channel producing membrane depolarization. Such membrane depolarization may contribute to slow feedback inhibition of store-operated calcium entry.
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PMID:Cyclic nucleotide-gated channels mediate membrane depolarization following activation of store-operated calcium entry in endothelial cells. 1076 97

cDNAs encoding a novel phosphodiesterase, phosphodiesterase 11A (PDE11A), were isolated by a combination of reverse transcriptase-polymerase chain reaction using degenerate oligonucleotide primers and rapid amplification of cDNA ends. Their catalytic domain was identical to that of PDE11A1 (490 amino acids) reported during the course of this study. However, the cDNAs we isolated had N termini distinct from PDE11A1, indicating two novel N-terminal variants of PDE11A. PDE11A3 cDNA encoded a 684-amino acid protein including one complete and one incomplete GAF domain in the N-terminal region. PDE11A4 was composed of 934 amino acids including two complete GAF domains and shared 630 C-terminal amino acids with PDE11A3 but had a distinct N terminus containing the putative phosphorylation sites for cAMP- and cGMP-dependent protein kinases. PDE11A3 transcripts were specifically expressed in testis, whereas PDE11A4 transcripts were particularly abundant in prostate. Recombinant PDE11A4 expressed in COS-7 cells hydrolyzed cAMP and cGMP with K(m) values of 3.0 and 1.4 microm, respectively, and the V(max) value with cAMP was almost twice that with cGMP. Although PDE11A3 showed the same K(m) values as PDE11A4, the relative V(max) values of PDE11A3 were approximately one-sixth of those of PDE11A4. PDE11A4, but not PDE11A3, was phosphorylated by both cAMP- and cGMP-dependent protein kinases in vitro. Thus, the PDE11A gene undergoes tissue-specific alternative splicing that generates structurally and functionally distinct gene products.
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PMID:Isolation and characterization of two novel phosphodiesterase PDE11A variants showing unique structure and tissue-specific expression. 1090 26

Previously we have shown that calcitonin gene-related peptide (CGRP), a neuropeptide increases lipopolysaccharide- (LPS) induced nitric oxide (NO) production in mouse peritoneal macrophages by using the Griess method. In this study we further examined whether CGRP could modulate inducible NO synthase (iNOS) protein and mRNA expression from mouse peritoneal macrophages. Macrophages were obtained from the peritoneal exude of male Balb/c mouse. The cells were plated on culture dishes at a density of 5 x 10(5) cells per well and were allowed to adhere for 2 h. After incubation for 24 h, the macrophages were cultured with 0.01 to 1 microg/mL LPS with or without CGRP (1-1,000 nM) for 24 h. The results showed that CGRP markedly enhanced 0.5 microg/mL LPS-induced NO release as compared with that of lower doses of LPS, such as 0.01 and 0.1 microg/mL LPS. NO was increased from 19.8 +/- 2.6 to the highest level of 31.5 +/- 4.2 microM in 5 x 10(5) cells by 10 nM CGRP in 0.5 microg/mL LPS-stimulated macrophages. The cGMP level in macrophages was augmented when CGRP was added with LPS. However, when using higher dose (1.0 microg/mL) of LPS to stimulate the macrophages, CGRP had no effect at all on NO release. CGRP had no direct effect on NO and cGMP production. CGRP increased the expression of inducible NOS protein in LPS-stimulated macrophages shown by immunocytochemistry method. The activity of iNOS was also enhanced by CGRP as compared with LPS-stimulation alone by detecting the 3H-L-citruline formation from 3H-L-arginine. We found that CGRP also increased the LPS-induced iNOS mRNA levels by using reverse transcriptase-PCR method. These data suggest that CGRP enhances LPS-induced NO release, iNOS activity, and iNOS mRNA in mouse peritoneal macrophages.
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PMID:Calcitonin gene-related peptide-enhanced nitric oxide release and inducible NOS activity and mRNA expression in LPS-stimulated mouse peritoneal macrophages. 1144 18

We have shown that cGMP-dependent protein kinase (PKG) mediates stimulation of L-type calcium current by cGMP in rabbit atrial myocytes. The human atrium may have similar PKG-dependent regulation of calcium current. To elucidate the significance of PKG in cardiac function, we have isolated human PKG type I alpha cDNA (+1 to 2016), determined the nucleotide sequence and analyzed specific expression of PKG in human atrium. We obtained full-length cDNA of PKG type I alpha from human atrial RNA using reverse transcriptase-polymerase chain reaction (RT-PCR). The coding region of human cardiac PKG I alpha showed 99.9% homology to previously published human PKG I alpha except for base No. 1983. At this position G was substituted for T and this resulted in an amino acid substitution from Leu649 to Phe649. The cloned PKG I alpha cDNA was expressed in COS cells and the expressed PKG showed cGMP-stimulated PKG enzyme activity and immunoreactivity. Ribonuclease protection assay, Western blot analysis, and PKG enzyme activity assays in homogenates from human atrial tissue demonstrated the presence of PKG mRNA and protein in human atrial tissue. Immunofluorescence staining confirmed that PKG is highly expressed in human atrial myocytes. These findings suggest that PKG is highly expressed in human atrium and that PKG-dependent phosphorylation may be important in regulation of calcium channel activity in human atrial myocytes.
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PMID:Expression of cGMP-dependent protein kinase in human atrium. 1144 35

To identify neural tumor cell lines that could be used as models to study growth-related natriuretic peptide actions, we determined the effects of these peptides on the proliferation of human and rodent neuroblastoma cell lines. Subnanomolar concentrations of atrial natriuretic peptide (ANP) and type C natriuretic peptide (CNP) stimulated proliferation in all four cell lines. These actions were associated with cGMP elevation and were blocked by a protein kinase G inhibitor. These data imply the involvement of guanylyl cyclase (GC)-coupled natriuretic receptors. However, higher concentrations of ANP and CNP, and low concentrations of des-[Gln(18),Ser(19),Gly(20),Leu(21),Gly(22)]-ANP(4-23)-NH(2) (desANP(4-23)) (analog for NPR-C receptor) exerted antiproliferative actions in three of the cell lines. These effects were insensitive to a protein kinase G inhibitor and to HS-142-1, suggesting that growth-inhibitory actions involved a non-GC receptor. They did not appear to involve cAMP, protein kinase A, protein kinase C, or calcium mobilization but were abolished when constitutive mitogen-activated protein kinase activity was inhibited. Radioligand binding experiments revealed the presence of a uniform class of binding sites in NG108 cells and multiple binding sites in Neuro2a cells. Northern and reverse transcriptase-polymerase chain reaction analyses revealed differential gene expression for NPR-A/B/C in NG108 and Neuro2a cells. The results indicate that natriuretic peptides stimulate neuroblastoma cell proliferation through type NPR-A/B (GC) receptors. Higher concentrations of ANP and CNP exerted a mitogen-activated protein kinase-dependent antiproliferative action mediated by a non-GC receptor that interacts with desANP(4-23) with relatively high affinity.
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PMID:Proliferative actions of natriuretic peptides on neuroblastoma cells. Involvement of guanylyl cyclase and non-guanylyl cyclase pathways. 1155 33

To characterize the functional differentiation of neural stem cells into smooth muscle cells, multipotent stem cells in the central nervous system (CNS) were isolated from rat embryonic day 14 (E14) cortex and cultured by neurosphere formation in serum-free medium in the presence of 10 ng ml(-1) of basic fibroblast growth factor. Differentiation was induced by the addition of 10 % fetal bovine serum to low-density cultures (2.5 x 10(3) cells cm(-2)). Immunological analyses and reverse transcriptase-polymerase chain reaction indicated that the differentiated cells expressed smooth-muscle-specific marker proteins such as SM-1, SM-2, and SMemb myosin heavy chains, SM-22, basic calponin and alpha-smooth-muscle actin, but not the astrocyte marker glial fibrillary acidic protein. To examine whether smooth-muscle-like cells that are differentiated from CNS stem cells possess the characteristics of contractile smooth muscle, we prepared reconstituted collagen gel fibres and measured their contractile tension. The reconstituted fibres were prepared by thermal gelation of collagen and the differentiated cells. The fibres contracted in response to treatment with KCl (80 mM), ACh (100 microM), endothelin-1 (10 nM), endothelin-2 (10 nM), and prostaglandin F2alpha (100 microM). ACh-induced contraction was partially inhibited by the L-type voltage-dependent Ca(2+) channel inhibitor nifedipine and by the intracellular Ca(2+) chelator 1,2-bis (2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester, the myosin light chain kinase inhibitor ML-9, the Rho kinase inhibitor Y-27632, dibutyryl cAMP and 8-bromo-cGMP. These results suggest that CNS stem cells give rise to smooth muscle cells in vitro that have an identical contractile function to smooth muscle in vivo.
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PMID:Contractile responses of smooth muscle cells differentiated from rat neural stem cells. 1192 76

The present study was aimed to investigate whether hyperglycemia may alter the regulation of vascular natriuretic peptide receptors (NPR). The hyperglycemia was induced in rats by the treatment with streptozotocin (50 mg/kg, i.v.). The expression of different subtypes of NPR was determined in the thoracic aorta by reverse transcriptase-polymerase chain reaction and quantitative in vitro receptor autoradiography. The isometric tension and the guanylyl cyclase activity of the isolated thoracic aorta in response to natriuretic peptides were also determined. Following the treatment with streptozotocin, the plasma concentration of atrial natriuretic peptide (ANP) was significantly increased. The expression of NPR-A was increased, while that of NPR-C was reduced. The receptor binding study demonstrated an increased maximal binding capacity of NPR, with its affinity not significantly altered. The magnitude of vasodilation and guanylyl cyclase activity in response to ANP was significantly increased. On the other hand, the vasodilator response as well as the tissue formation of cGMP in response to acetylcholine or sodium nitroprusside was significantly reduced. These results indicate that the hyperglycemia may cause an altered regulation of vascular NPR.
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PMID:Augmented natriuretic peptide-induced guanylyl cyclase activity and vasodilation in experimental hyperglycemic rats. 1192 17

Developmental changes (from 2 to 26 weeks) in phosphodiesterase (PDE) activity in the rat submandibular gland were investigated. Major activities for both cAMP- and cGMP-PDE were present in the 100000 x g supernatant fractions (70-90% of total activities), but not in the pellet fractions, during development. The effects of stimulators (Ca(2+)/calmodulin and cGMP) and inhibitors (cGMP, cilostamide, rolipram and zaprinast) were investigated in the supernatant fractions. During development, PDE4 (cAMP-specific PDE) was a major PDE, indicating that the majority of cAMP is hydrolysed by PDE4. In the young rat, PDE1 hydrolysed cGMP three-fold more than the control, and PDE2 (cGMP-stimulated PDE) was present, indicating that the concentration of intracellular cGMP may be enhanced, and cGMP may function in the growth pathway in the submandibular gland. Chromatograms eluted on a Mono Q HR5/5 ion-exchange column supported the results of the inhibition studies: PDE1, PDE2, PDE3, PDE4 and PDE5 were present in the young submandibular gland, and PDE1, PDE3, PDE4 and PDE5 in the adult gland. Expression of PDE5 was detected by inhibition studies, reverse transcriptase-polymerase chain reaction and Western blotting in the submandibular gland.
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PMID:Changes in phosphodiesterase activity in the developing rat submandibular gland. 1222 Oct 13

Guanylyl cyclase C (GC-C) is a membrane-associated form of guanylyl cyclase and serves as the receptor for the heat-stable enterotoxin (ST) peptide and endogenous ligands guanylin, uroguanylin, and lymphoguanylin. The major site of expression of GC-C is the intestinal epithelial cell, although GC-C is also expressed in extraintestinal tissue such as the kidney, airway epithelium, perinatal liver, stomach, brain, and adrenal glands. Binding of ligands to GC-C leads to accumulation of intracellular cGMP, the activation of protein kinases G and A, and phosphorylation of the cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel that regulates salt and water secretion. We examined the expression of GC-C and its ligands in various tissues of the reproductive tract of the rat. Using reverse transcriptase and the polymerase chain reaction, we demonstrated the presence of GC-C, uroguanylin, and guanylin mRNA in both male and female reproductive organs. Western blot analysis using a monoclonal antibody to GC-C revealed the presence of differentially glycosylated forms of GC-C in the caput and cauda epididymis. Exogenous addition of uroguanylin to minced epididymal tissue resulted in cGMP accumulation, suggesting an autocrine or endocrine activation of GC-C in this tissue. Immunohistochemical analyses demonstrated expression of GC-C in the tubular epithelial cells of both the caput epididymis and cauda epididymis. Our results suggest that the GC-C signaling pathway could converge on CFTR in the epididymis and perhaps control fluid and ion balance for optimal sperm maturation and storage in this tissue.
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PMID:Expression of the receptor guanylyl cyclase C and its ligands in reproductive tissues of the rat: a potential role for a novel signaling pathway in the epididymis. 1244 76


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