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:3.2.1.23 (beta-galactosidase)
14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric oxide (NO) can modulate numerous genes through several pathways, yet some genes may be modulated only in the presence of the inflammatory stimuli that upregulate the inducible nitric oxide synthase (iNOS) rather than by NO alone. Furthermore, the role of prior expression of iNOS in the modulation of genes by NO is unknown. We addressed these issues in hepatocytes harvested from iNOS-null (iNOS(-/-)) mice exposed to NO by treatment with NO donors or by infection with an adenovirus-expressing human iNOS (Ad-iNOS), rather than by stimulation with inflammatory cytokines. Differential display and gene array analyses performed on mRNA derived from iNOS(-/-) hepatocytes demonstrated that infection with Ad-iNOS, but not infection with a control adenovirus expressing the beta-galactosidase gene (Ad-LacZ), induced a gene fragment identical to cytochrome P450 2E1 (CYP2E1). Northern analysis performed with this fragment demonstrated that treatment of iNOS(-/-) hepatocytes with Ad-iNOS or with the NO donor S-nitroso-N-acetyl-d,l-penicillamine (SNAP), but not control treatment or infection with Ad-LacZ, resulted in increased expression of CYP2E1. Inhibition of soluble guanylyl cyclase partially blocked the induction of CYP2E1 mRNA by Ad-iNOS. Rat hepatocytes treated with SNAP also exhibited increased expression of CYP2E1 mRNA. Preliminary studies, however, suggest that the induction of CYP2E1 in the rat hepatocytes treated with cytokines was not reduced in the presence of a NOS inhibitor. Our results suggest that CYP2E1 can be induced solely by NO derived from iNOS, at least partly in a cyclic GMP-dependent manner and independently of inflammatory stimuli or of prior exposure to NO.
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PMID:Nitric oxide from the inducible nitric oxide synthase (iNOS) increases the expression of cytochrome P450 2E1 in iNOS-null hepatocytes in the absence of inflammatory stimuli. 1139 31

The nucleus tractus solitarii (NTS) is an important site for the regulation of sympathetic nerve activity. It receives the signals through afferent fibers from arterial baroreceptors, chemoreceptors, cardiopulmonary receptors, and other visceral receptors. Many studies have examined the role of nitric oxide (NO) in the NTS in cardiovascular regulation. However, most of these studies were conducted in an acute state with anesthesia. We have developed a novel technique of endothelial nitric oxide synthase (eNOS) gene transfer into the NTS in vivo. Adenovirus vectors encoding either the beta-galactosidase gene (Ad beta gal) or the endothelial nitric oxide synthase gene (AdeNOS) gene were transfected into the NTS. In the Ad beta gal-treated rats, the local expression of beta-galactosidase was confirmed by X-Gal staining, and beta-galactosidase activity was quantified using a colorimetric assay. In the AdeNOS-treated rats, the local expression of eNOS protein was confirmed by immunohistochemistry, and eNOS production was measured by in vivo microdialysis. Blood pressure and heart rate were monitored by a radiotelemetry system in a conscious state. The expression of each gene was observed from day 5 to day 10 after the gene transfer. In the AdeNOS-treated rats, blood pressure and heart rate significantly decreased from day 5 to day 10, and then thereafter gradually recovered over time. Our method may be useful in examining the local effect of a particular substance produced by a specific gene in the brain on cardiovascular function.
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PMID:Adenovirus-mediated gene transfer into the NTS in conscious rats. A new approach to examining the central control of cardiovascular regulation. 1145 77

The purpose of this study was to determine the effects of interferon-beta (IFN-beta) gene transfer on the growth of PC3MM2 human prostate cancer cells in nude mice. Intralesional delivery of an adenoviral vector encoding murine IFN-beta (AdIFN-beta), but not a vector encoding bacterial beta-galactosidase (AdLacZ), suppressed PC3MM2 tumors in a dose-dependent manner. At the highest dose (2x10(9) plaque-forming units, PFU), a single injection of AdIFN-beta (but not AdLacZ) suppressed orthotopic PC3MM2 tumors and development of metastasis by 80%, and eradicated the tumors in 20% of mice. Immunohistochemical staining showed that AdIFN-beta-treated tumors contained fewer microvessels, fewer proliferating cells, and more apoptotic cells than did the control tumors. Compared with controls, tumors injected with AdIFN-beta expressed higher levels of IFN-beta and inducible nitric oxide synthase (iNOS) and lower levels of basic fibroblast growth factor (bFGF) and transforming growth factor beta1 (TGF-beta1). In vitro analysis indicated that expression of bFGF and TGF-beta1 in PC3MM2 cells could be suppressed by the nitric oxide donor sodium nitroprusside. These data suggest that intratumoral delivery of the IFN-beta gene with adenoviral vectors could be an effective therapy for prostate cancer and that tumor suppression by AdIFN-beta correlated with up-regulation of iNOS and down-regulation of angiogenesis.
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PMID:Adenovirus-mediated interferon-beta gene therapy suppresses growth and metastasis of human prostate cancer in nude mice. 1149 71

The clinical outcome of vascular stenting is limited by in-stent stenosis. Increased nitric oxide (NO)/cGMP signaling by L-arginine (L-Arg) supplementation, the substrate for NO synthase (NOS), or NOS gene transfer may reduce in-stent neointima formation. After stenting, vascular cell proliferation in rat carotid arteries, as measured by 5'-bromodeoxyuridine (5'-BrdU) incorporation, indicated 15+/-8%, 28+/-5%, and 33+/-7% 5'-BrdU-positive vascular cells at 4, 7, and 14 days, respectively. Reporter beta-galactosidase gene transfer efficacy was evidenced by 30% beta-galactosidase-expressing medial smooth muscle cells at 14 days. The intima-to-media ratio (I/M) progressively increased to 2.32+/-0.24 at 14 days. To target in-stent neointima formation, animals were infected with adenoviral vectors (4x10(10) plaque-forming units per mL) expressing NOS2 (AdNOS2) or no transgene (AdRR5), or they received daily doses of L-Arg (500 mg. kg(-1). (d-1) IP). The neointima at 14 days was smaller in L-Arg-treated than in untreated rats (I/M 1.25+/-0.35 vs 2.32+/-0.24, P<0.05, n=7 each) or in AdRR5- and AdNOS2-infected rats (I/M 2.57+/-0.43, n=7 and 1.82+/-0.75, n=8, respectively; P<0.05 for both). The effect of L-Arg was abolished by simultaneous administration of N(G)-nitro L-arginine methyl ester, an NOS inhibitor (2.03+/-0.39, P<0.05, vs L-Arg). Inflammation was markedly less in L-Arg- and AdNOS2-treated than in AdRR5-infected rats. Supplemental L-Arg reduces neointima formation after stenting by way of an NOS-dependent mechanism and may be a valuable strategy to target in-stent stenosis.
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PMID:L-arginine administration reduces neointima formation after stent injury in rats by a nitric oxide-mediated mechanism. 1159 33

The paraventricular nucleus (PVN) of the hypothalamus is known to be involved in the control of sympathetic outflow. Nitric oxide (NO) has been shown to have a sympathoinhibitory effect in the PVN. The goal of the present study was to examine the influence of overexpression of neuronal NO synthase (nNOS) within the PVN on renal sympathetic nerve discharge (RSND). Adenovirus vectors encoding either nNOS (Ad.nNOS) or beta-galactosidase (Ad.beta-Gal) were transfected into the PVN in vivo. Initially, the dose of adenovirus needed for infection was determined from in vitro infection of cultured fibroblasts. In Ad.nNOS-treated rats, the local expression of nNOS within the PVN was confirmed by histochemistry for NADPH-diaphorase-positive neurons. There was a robust increase in staining of NADPH-diaphorase-positive cells in the PVN on the side injected with Ad.nNOS. The staining peaked at 3 days after injection of the virus. In alpha-chloralose- and urethane-anesthetized rats, microinjection of N(G)-monomethyl-L-arginine (L-NMMA), a NO antagonist, into the PVN produced a dose-dependent increase in RSND, blood pressure, and heart rate. There was a potentiation of the increase in RSND, blood pressure, and heart rate due to L-NMMA in Ad.nNOS-injected rats compared with Ad.beta-Gal-injected rats. These results suggest that the endogenous NO-mediated effect in the PVN of Ad.nNOS-treated rats is more effective in suppressing RSND compared with Ad.beta-Gal-treated rats. These observations support the contention that an overexpression of nNOS within the PVN may be responsible for increased suppression of sympathetic outflow. This technique may be useful in pathological conditions know to have increased sympathetic outflow, such as hypertension or heart failure.
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PMID:Effect of in vivo gene transfer of nNOS in the PVN on renal nerve discharge in rats. 1178 7

Salmonella typhimurium TA4107/pSK1002 strain was used to measure the SOS response induced by peroxynitrite. The parent strain TA4107 (oxydelta1[oxydelta(oxyR argH)1]) is sensitive to oxidative stress and the plasmid of pSK1002 carries a fused gene umuC'-'lacZ, in which umu and lacZ genes are involved in the induction of mutagenesis and beta-galactosidase activity, respectively. Therefore, the level of SOS response was monitored via beta-galactosidase activity. A bolus addition of authentic peroxynitrite (0.3-0.6 mM) increased about eight times the enzyme activity. In N-morpholino sydnonimine (SIN-1), which produces peroxynitrite from superoxide and nitric oxide generated through hydrolysis, addition of over 1mM SIN-1 induced four-five-fold activity. The SIN-1-induced SOS response was scarcely influenced by superoxide dismutase (SOD), catalase or a combination of both, removing the possibility of induction by superoxide, hydrogen peroxide and hydroxyl radical. Two types of peroxynitrite scavengers, mannitol (type I) and glutathione (type II), decreased the response. Mannitol showed a constant inhibition (70%) at a concentration up to 20 mM, exhibiting kinetics that are zero-order in mannitol and first-order in peroxynitrite. On the other hand, glutathione sharply reduced the response dependent on concentration up to 2 mM (90%), indicating second-order kinetics, first-order in both glutathione and peroxynitrite. Dihydrorhodamine (DHR)123, which traps peroxynitrite in a molar ratio of 1:1, efficiently inhibited the SOS response. These effects suggest that peroxynitrite, generated gradually from SIN-1, penetrates through the cell membrane, damages the DNA and induces the SOS response. This strain can thus, be used in screening of antioxidants against peroxynitrite-induced DNA damage in cells.
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PMID:Induction of SOS response in Salmonella typhimurium TA4107/pSK1002 by peroxynitrite-generating agent, N-morpholino sydnonimine. 1199 67

The present study was designed to determine the effect of recombinant inducible nitric oxide (NO) synthase (iNOS) gene expression on vasomotor function in cerebral arteries. Isolated canine basilar arteries were exposed ex vivo (30 min at 37 degrees C) to an adenoviral vector [10(7), 10(8), or 10(9) plaque-forming units (pfu)/ml] encoding either the iNOS gene or the beta-galactosidase reporter gene. Twenty-four hours after transduction, Western blot analysis demonstrated expression of iNOS protein only in iNOS (10(9) pfu/ml)-transduced arteries. Immunohistochemical analysis localized iNOS expression predominantly in adventitia. Vascular reactivity of isolated basilar arteries was studied by isometric force recording. Concentration-response curves to UTP (10(-9)-10(-3) M) and diethylaminodiazen-1-ium-1,2-dioate (10(-10)-10(-5) M) were significantly shifted to the right in iNOS gene (10(9) pfu/ml)-transduced rings compared with control and beta-galactosidase-transduced rings (P < 0.05, n = 5-6). Endothelium-dependent relaxation to bradykinin was significantly attenuated in iNOS-transduced rings (P < 0.001, n = 8). The basal level of cGMP and superoxide anion (O(2)(-).) production were elevated in iNOS-transduced rings (P < 0.05, n = 7 for cGMP; P < 0.01, n = 6-9 for O(2)(-). production). Our results suggest that expression of recombinant iNOS in cerebral arteries reduces vasomotor reactivity to both vasoconstrictor and vasodilator agonists. Attenuation of contractions is most likely due to functional antagonism between UTP and cGMP. Reduction of endothelium-dependent relaxation to bradykinin appears to be mediated in part by reduced reactivity of smooth muscle cells to NO.
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PMID:Inhibitory effect of recombinant iNOS gene expression on vasomotor function of canine basilar artery. 1238 12

The genes norCBQD that encode the bc-type nitric oxide reductase from Bradyrhizobium japonicum USDA110 have been isolated and characterized. norC and norB encode the cytochrome c-containing subunit II and cytochrome b-containing subunit I of nitric oxide reductase, respectively. norQ encodes a protein with an ATP/GTP-binding motif, and the predicted norD gene product shows similarity with NorD from other denitrifiers. Mutational analysis indicates that the two structural norC and norB genes are required for microaerobic growth under nitrate-respiring conditions. A mutant strain lacking a functional norC gene also lacked the 16 kDa c-type cytochrome that is normally detectable by haem-staining of proteins from membranes of microaerobically grown wild-type cells. Expression of a transcriptional fusion of the nor promoter region to the reporter gene lacZ (P(norC)-lacZ) was not detected in aerobically grown cells of USDA110, but the fusion was induced threefold when the cells were cultured under microaerobic conditions (1% O(2)) with either nitrite or nitric oxide, and about 18-fold when nitrate was the N oxide present in the medium. The P(norC)-lacZ fusion was not expressed in the B. japonicum fixK(2) mutant strain 9043, but complementation of the mutant with the fixK(2) gene restored beta-galactosidase activity to levels similar to those found in the parental strain. The promoter region of the norCBQD genes has been characterized by primer extension. A major transcript initiates 45.5 bp downstream of the centre of a putative binding site for the transcription factor FixK(2).
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PMID:Characterization of the norCBQD genes, encoding nitric oxide reductase, in the nitrogen fixing bacterium Bradyrhizobium japonicum. 1242 46

The manganese superoxide dismutase (MnSOD) is a mitochondrial enzyme that dismutates a potentially toxic superoxide radical into hydrogen peroxide and dioxygen. To study the regulation of the Schizosaccharomyces pombe MnSOD gene, the 943 bp upstream region was fused into the promoterless beta-galactosidase gene of the shuttle vector YEp357, which resulted in the fusion plasmid pMS14. Restriction mapping and nucleotide sequencing confirmed its construction. The synthesis of beta-galactosidase from the fusion plasmid was induced by aluminum chloride, menadione, cadmium chloride, manganese chloride, and hydrogen peroxide. It was also induced by NO-generating S-nitroso-N-acetylpenicillamine (SNAP). However, cupric chloride and zinc chloride did not affect the synthesis of beta-galactosidase from the fusion plasmid. The beta-galactosidase synthesis appeared to be independent of the Pap1 protein. These results suggest that some metals, oxidative stress, and nitric oxide regulate the S. pombe MnSOD gene.
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PMID:Regulation of the manganese-containing superoxide dismutase gene from fission yeast. 1244 5

The myofibroblast shares phenotypic features of both fibroblasts and smooth muscle cells. It plays a critical role in collagen deposition and wound healing and disappears by apoptosis when the wound is closed. Its abnormal persistence leads to hypertrophic scar formation and other fibrotic conditions. Myofibroblasts are present in the fibrotic plaque of the tunica albuginea (TA) of the penis in men with Peyronie's disease (PD), a localized fibrosis that is accompanied by a spontaneous induction of the inducible nitric oxide synthase (iNOS), also observed in the TGFbeta1-elicited, PD-like lesion in the rat model. iNOS expression counteracts fibrosis, by producing nitric oxide (NO) that reduces collagen deposition in part by neutralization of profibrotic reactive oxygen species. In this study we investigated whether fibroblast differentiation into myofibroblasts is enhanced in the human and rat PD-like plaque and in cultures of human tissue fibroblasts. We also examined whether NO reduces this cell differentiation and collagen synthesis. The myofibroblast content in the fibroblast population was measured by quantitative immunohistochemistry as the ratio between alpha-smooth muscle actin (ASMA; myofibroblast marker) and vimentin (general fibroblast marker) levels. We found that myofibroblast content was considerably increased in the human and TGFbeta1-induced rat plaques as compared to control TA. Inhibition of iNOS activity by chronic administration of L-iminoethyl-L-lysine to rats with TGFbeta1-induced TA lesion increased myofibroblast abundance and collagen I synthesis measured in plaque and TA homogenates from animals injected with a collagen I promoter construct driving the expression of beta-galactosidase. Fibroblast differentiation into myofibroblasts occurred with passage in the cell cultures from the human PD plaque, but was minimal in cultures from the TA. Induction of iNOS in PD and TA cultures with a cytokine cocktail and a NO donor, S-nitroso-N-acetyl penicillamine (SNAP), was detected by immunohistochemistry. Both treatments reduced the total number of cells and the number of ASMA positive cells, whereas only SNAP decreased collagen I immunostaining. These results support the hypotheses that myofibroblasts play a role in the development of the PD plaque and that the antifibrotic effects of NO may be mediated at least in part by the reduction of myofibroblast abundance and lead to a reduction in collagen I synthesis.
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PMID:Effect of nitric oxide on the differentiation of fibroblasts into myofibroblasts in the Peyronie's fibrotic plaque and in its rat model. 1244 75


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