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)

Gaseous nitrogen dioxide (NO2) was found to induce umuC gene expression in Salmonella typhimurium carrying the umuC-lacZ fusion plasmid. The induction level of the umu operon responsible for inducible mutagenesis was measured by the level of beta-galactosidase in the cell, encoded by the fusion gene. NO2 gas was bubbled into bacterial suspensions at 10, 30 and 90 microliters/l for 30 min at a flow rate of 100 ml/min. Expression of the umuC gene varied with the concentration, flow rate and bubbling time of the NO2 gas. Although NO2 gas induces SOS functions, mutagenesis due to it was not detectable in Salmonella typhimurium TA100 and TA102. Nitric oxide gas (NO) did not induce any umuC gene expression.
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PMID:Induction of umuC gene expression by nitrogen dioxide in Salmonella typhimurium. 388 44

It is postulated that vascular disease involves a disturbance in the homeostatic balance of factors regulating vascular tone and structure. Recent developments in gene transfer techniques have emerged as an exciting therapeutic option to treat vascular disease. Several studies have established the feasibility of direct in vivo gene transfer into the vasculature by using reporter genes such as beta-galactosidase or luciferase. To date no study has documented therapeutic effects with in vivo gene transfer of a cDNA encoding a functional enzyme. This study tests the hypothesis that endothelium-derived nitric oxide is an endogenous inhibitor of vascular lesion formation. After denudation by balloon injury of the endothelium of rat carotid arteries, we restored endothelial cell nitric oxide synthase (ec-NOS) expression in the vessel wall by using the highly efficient Sendai virus/liposome in vivo gene transfer technique. ec-NOS gene transfection not only restored NO production to levels seen in normal untreated vessels but also increased vascular reactivity of the injured vessels. Neointima formation at day 14 after balloon injury was inhibited by 70%. These findings provide direct evidence that NO is an endogenous inhibitor of vascular lesion formation in vivo (by inhibiting smooth muscle cell proliferation and migration) and suggest the possibility of ec-NOS transfection as a potential therapeutic approach to treat neointimal hyperplasia.
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PMID:Gene therapy inhibiting neointimal vascular lesion: in vivo transfer of endothelial cell nitric oxide synthase gene. 753 5

Nitric oxide (NO), a vasodilator involved in the regulation of pulmonary vascular tone, is synthesized by a family of enzymes, nitric oxide synthases (NOS). To investigate whether adenoviral-mediated overexpression of constitutive endothelial NOS (ceNOS) would attenuate hypoxic pulmonary vasoconstriction, we aerosolized 3 X 10(9) plaque forming units of a recombinant adenovirus containing the ceNOS gene (AdCMVceNOS) into rat lungs. Four days after infection, transgene expression was confirmed using immunoblot techniques. Diffuse ceNOS immunostaining was detected in alveoli and medium-sized and small pulmonary vessels of AdCMVceNOS-transduced lungs. AdCMVceNOS-transduction was associated with an 86% increase in [3H]arginine to [3H]citrulline conversion and a rise in pulmonary cGMP levels from 7 +/- 1 to 59 +/- 9 pmol/mg protein in lungs from AdCMVceNOS versus control rats, (P < 0.05). During acute hypoxia (FIO2 = 0.10) for 25 min, mean pulmonary artery pressure (PAP) increased significantly from 17 +/- 1 to 27 +/- 1 mmHg in rats aerosolized with saline (n = 4) and from 18 +/- 1 to 28 +/- 1 mmHg in rats given an adenoviral vector expressing a nuclear-targeted beta-galactosidase gene (AdCMV beta gal, n = 8). In contrast, in AdCMVceNOS-transduced rats (n = 8) the hypoxia-induced increase in PAP was significantly attenuated (18 +/- 1 to 23 +/- 2 mmHg). Systemic blood pressure was not affected by aerosol gene transfer. Thus, adenoviral-mediated ceNOS gene transfer to rat lungs increases ceNOS expression and activity, and reduces acute hypoxic pulmonary vasoconstriction. Aerosolized recombinant adenovirus overexpressing vasodilatory proteins can act as a selective pulmonary vasodilator and may hold promise as a future therapeutic strategy for pulmonary hypertension.
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PMID:Adenoviral-mediated transfer of the human endothelial nitric oxide synthase gene reduces acute hypoxic pulmonary vasoconstriction in rats. 875 40

To examine whether nitric oxide (NO) has a protective effect against Ca2+ overdose or a beneficial action on myocardial cells, we employed direct gene-transfer of endothelial (type III) nitric oxide synthase (eNOS), using HVJ (Sendai virus) coated liposomes and beta-galactosidase (lac-z) as a marker for the transfection. The transfection efficiency of the lac-z gene was comparable with adenovirus as a vector, though the subsequent inflammation was much improved. The lac-z gene transfection was restricted to myoplasm between two intercalated discs, indicating that the transfected gene dose not permeate the disc. Co-transfection with human eNOS gene revealed degraded myoplasm of not only transfected cells but adjacent myocytes, fibrotic changes and infiltration of mononuclear cells seven days after the transfection. Electron microscopy of the lesions revealed a huge accumulation of mitochondria and loss of myofilaments, though fragmentation of nucleus or cytoplasm was not obvious. We conclude that an expression of human eNOS gene in cardiomyocytes causes a degenerative process, incompatible with typical apoptosis.
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PMID:Toxic action of nitric oxide on myocardial cells: direct evidence from gene transfer in vivo. 895 73

Gene transfer with replication-deficient adenovirus is a potentially useful tool to study vascular biology. We have constructed a replication-deficient adenovirus (AdRSVeNOS) that carries cDNA for endothelial nitric oxide synthase (eNOS). Transfection of COS-1 cells with AdRSVeNOS increased nitric oxide synthase activity (measured as production of L-citrulline from L-arginine) that was calcium dependent and inhibited by N omega-nitro-L-arginine methyl ester. To investigate effects of overexpression of eNOS on vascular function, we incubated common carotid arteries from rabbits in organ culture with AdRSVeNOS or AdRSV beta gal encoding beta-galactosidase. Transgene expression and responses to vasoactive agents were examined 1 day after transduction. Histochemical staining of beta-galactosidase and immunohistochemistry for eNOS indicated transgene expression in endothelium and adventitial cells. After precontraction with phenylephrine, vessels treated with AdRSVeNOS demonstrated greater relaxation to acetylcholine than vessels treated with vehicle or AdRSV beta gal. Relaxation to calcium ionophore A-23187 was much greater in vessels treated with AdRSVeNOS than in vessels treated with vehicle or AdRSV beta gal. Augmented relaxation in response to A-23187 was also observed after denudation of endothelium in vessels treated with AdRSVeNOS and was inhibited by N omega-nitro-L-arginine. Thus vasorelaxation in response to stimuli that release nitric oxide is augmented after adenovirus-mediated overexpression of eNOS. Transgene expression in adventitial cells appears to be sufficient to alter vasomotor function.
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PMID:Altered vascular function after adenovirus-mediated overexpression of endothelial nitric oxide synthase. 924 99

Nitric oxide (NO), synthesized from L-arginine by NO synthases (NOS), plays an essential role in the regulation of cerebrovascular tone. Adenoviral vectors have been widely used to transfer recombinant genes to different vascular beds. To determine whether the recombinant endothelial NOS (eNOS) gene can be delivered in vivo to the adventitia of cerebral arteries and functionally expressed, a replication-incompetent adenoviral vector encoding eNOS gene (AdCMVNOS) or beta-galactosidase reporter gene (AdCMVLacZ) was injected into canine cerebrospinal fluid (CSF) via the cisterna magna (final viral titer in CSF, 10(9) pfu/ml). Adventitial transgene expression was demonstrated 24 h later by beta-galactosidase histochemistry and quantification, eNOS immunohistochemistry, and Western blot analysis of recombinant eNOS. Electron microscopy immunogold labeling indicated that recombinant eNOS protein was expressed in adventitial fibroblasts. In AdCMVNOS-transduced arteries, basal cGMP production and bradykinin-induced relaxations were significantly augmented when compared with AdCMVLacZ-transduced vessels (P < 0.05). The increased receptor-mediated relaxations and cGMP production were inhibited by eNOS inhibitors. In addition, the increase in cGMP production was reversed in the absence of calcium, suggesting that the increased NO production did not result from inducible NOS expression. The present study demonstrates the successful in vivo transfer and functional expression of recombinant eNOS gene in large cerebral arteries. It also suggests that perivascular eNOS gene delivery via the CSF is a feasible approach that does not require interruption of cerebral blood flow.
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PMID:Effects of in vivo adventitial expression of recombinant endothelial nitric oxide synthase gene in cerebral arteries. 935 90

Thickening of the arterial intima and smooth muscle cell (SMC) proliferation remain major problems after vascular surgery and other types of vascular manipulations. We studied the effect of endothelial cell (EC)-specific vascular endothelial growth factor (VEGF) gene transfer on the thickening of the intima using a silicone collar inserted around carotid arteries that acted both as the agent that caused intimal SMC growth and as a reservoir for the transfected gene. The model preserved EC integrity and permitted direct extravascular gene transfer without any intravascular manipulation. Compared to beta-galactosidase (lacZ)-transfected control arteries, plasmid/liposome-mediated VEGF gene transfer significantly reduced intimal thickening 1 week after the gene transfer. Administration to the experimental animals of the nitric oxide (NO) synthase inhibitor L-NAME abolished the difference in intimal thickening between VEGF and lacZ-transfected arteries. Furthermore, VEGF caused NO release from cultured human umbilical vein EC. It is concluded that extravascular VEGF gene transfer attenuates intimal growth and could be useful for the prevention of intimal thickening during vascular surgery. Our results further suggest that VEGF may reduce SMC proliferation via a mechanism that involves VEGF-induced NO production from the endothelium.
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PMID:VEGF gene transfer reduces intimal thickening via increased production of nitric oxide in carotid arteries. 935 23

2-Methoxyestradiol (2ME) is an endogenous metabolite of estradiol (E2) and is known to inhibit tumor angiogenesis. In the present study, the direct effects of 2ME on the vascular endothelial cells were examined. 2ME enhanced apoptosis and beta-galactosidase expression in bovine vascular endothelial cells. A nitric oxide (NO) donor S-nitroso-N-acetyl penicillamin (SNAP) also enhanced beta-galactosidase expression, suggesting a possible role of NO in mediating the action of 2ME. 2ME increased the cellular content of nitric oxide synthase (NOS) and the production of NO. In addition, 2ME altered the membrane localization pattern of NOS. These suggest that the effects of 2ME on apoptosis and senescence of vascular endothelial cells were mediated, at least partly, by NOS and NO.
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PMID:2-Methoxyestradiol, an endogenous metabolite of estrogen, enhances apoptosis and beta-galactosidase expression in vascular endothelial cells. 967 76

TNP470, a derivative of fumagillin, suppressed in vivo growth of human PLC/PRF/5 hepatoma and ameliorated cachexia of hepatoma-bearing mice. These in vivo effects were associated with reductions in microvessel and macrophage counts. In in vitro experiments, TNP470 inhibited the growth and migration of human hepatoma and bovine vascular endothelial (VE) cells. TNP470 did not inhibit the production of VE growth factor by the hepatoma, which suggests that this compound acts directly on VE cells in vivo. In contrast, TNP470 inhibited the production of leukemia inhibitory factor, which may be related to the amelioration of cancer cachexia. TNP470 induced apoptosis and enhanced the expression of beta-galactosidase, a biomarker of senescence, which was partly mimicked by a nitric oxide (NO) donor S-nitroso-N-acetyl penicillamin. TNP470 inhibited myristoylation and membrane translocation of NO synthase and increased the cellular content of NO synthase and production of NO. Therefore, it is suggested that the actions of TNP470 are mediated, at least in part, through the inhibition of membrane translocation of biologically active proteins.
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PMID:Suppression of hepatoma growth and angiogenesis by a fumagillin derivative TNP470: possible involvement of nitric oxide synthase. 972 89

Gene transfer with replication-deficient adenovirus is a useful tool to study vascular biology. We have reported that overexpression of endothelial nitric oxide (NO) in carotid arteries from normal rabbits augments vasorelaxation mediated by NO. In this study, we tested the hypothesis that adenovirus-mediated gene transfer of endothelial nitric oxide synthase (eNOS) improves impaired relaxation of atherosclerotic vessels. We used 2 replication-deficient adenoviruses: AdeNOS, which carries cDNA for eNOS, and Adbetagal, which expresses beta-galactosidase. Common carotid arteries from 10 New Zealand White (NZW; plasma cholesterol, 79+/-13 mg/dL) and 10 Watanabe heritable hyperlipidemic (WHHL; plasma cholesterol, 452+/-39 mg/dL) rabbits were incubated in organ culture with AdeNOS, Adbetagal, or vehicle alone. Carotid arteries from WHHL rabbits had mild to moderate atherosclerotic lesions. Histochemical staining for beta-galactosidase and immunohistochemistry for eNOS indicated transgene expression in the endothelium and adventitia in both NZW and WHHL rabbits. Expression of eNOS determined with Western blot analysis after incubation with AdeNOS tended to be higher in vessels from WHHL rabbits than NZW rabbits. Effects of transgene expression on vascular function were examined by recording isometric tension 1 day after transduction. After precontraction with phenylephrine, acetylcholine produced significantly less relaxation in vessels from WHHL rabbits than in vessels from NZW rabbits. Relaxation in response to acetylcholine was greater in carotid arteries from both NZW and WHHL rabbits that were transfected with AdeNOS than in vessels treated with vehicle or Adbetagal. Vasorelaxation in response to acetylcholine was inhibited by Nomega-nitro-L-arginine. Responses to sodium nitroprusside were similar after treatment with vehicle alone, Adbetagal, or AdeNOS in both groups of rabbits. Thus, overexpression of eNOS with an adenoviral vector improves impaired NO-mediated relaxation in atherosclerotic arteries.
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PMID:Improvement of relaxation in an atherosclerotic artery by gene transfer of endothelial nitric oxide synthase. 981 14


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