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:3.5.4.17 (adenosine deaminase)
5,206 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

By virtue of its immediate contact with the circulating blood, the endothelium provides an attractive target for retroviral vector transduction for the purpose of gene therapy. To see whether efficient gene transfer and expression was feasible, rabbit aortic endothelial cells were infected with three Moloney murine leukemia virus-derived retroviral vectors. Two of these vectors carry genes encoding products that are not secreted: N2, containing only the selectable marker gene neoR, and SAX, containing both neoR gene and an SV40-promoted adenosine deaminase (ADA) gene. The third vector, G2N, contains a secretory rat growth hormone (rGH) gene and an SV40-promoted neoR gene. Infection with all three vectors resulted in expression of the respective genes. A high level of human ADA expression was observed in infected endothelial cell populations both before and after selection in G418. G2N-infected rabbit aortic endothelial cells that were grown on a synthetic vascular graft continued to secrete rGH into the culture medium. These studies suggest that endothelial cells may serve as vehicles for the introduction in vivo of functioning recombinant genes.
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PMID:High-level recombinant gene expression in rabbit endothelial cells transduced by retroviral vectors. 291 35

Patients with tumors secreting vasoactive intestinal peptide (VIP) often develop hyperglycemia and glucose intolerance. Although VIP has been reported to increase glucose output by the liver, the concentration required for this effect greatly exceeds that observed clinically. We therefore investigated the effects of VIP on insulin-stimulated glucose transport in isolated adipocytes. Inhibition of insulin action was observed at a concentration of 1 ng/ml VIP with half-maximal inhibition at approximately 20 ng/ml. 125I-VIP bound to specific high-affinity sites on the adipocytes. Fifty percent inhibition of binding occurred at a concentration of unlabeled VIP of approximately 10 ng/ml and was not affected by insulin, glucagon, or growth hormone. As we have observed previously with glucagon and catecholamines, inhibition of insulin action by VIP was observed only when accumulation of adenosine in the incubation medium was prevented by addition of adenosine deaminase. Under these conditions VIP markedly increased cellular cAMP levels. A good correlation was observed among VIP binding, inhibition of insulin-stimulated glucose transport, and cellular concentrations of cAMP. The results suggest that inhibition of insulin action in adipose tissue contributes to the hyperglycemic effect of VIP. Together, with our published findings on glucagon and catecholamines, these results support the hypothesis that counterregulatory hormones inhibit insulin action by increasing cellular concentrations of cAMP.
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PMID:Vasoactive intestinal peptide inhibits insulin-stimulated glucose transport in rat adipocytes. 300 79

Interspecific somatic cell hybrid clones have been isolated and characterized in order to study growth hormone (GH) and prolactin (PRL) gene expression. Rat pituitary tumor cells (GH3, 69 chromosomes) secreting rat GH and PRL were grown for 48 h together with nonhormone secreting, aminopterin-sensitive murine fibroblast cells (LMTK-, 55 chromosomes) and fused using polyethylene glycol. Resultant heterokaryons were selected in hypoxanthine-aminopterin-thymidine (HAT) medium and cloned. Five clones produced rat GH and PRL. Hormone-producing hybrids morphologically resembled the mouse parent fibroblast. Hybrids grew in monolayers and contained 80-142 chromosomes, and marker chromosomes for both rat (small submetacentric) and mouse (bi-armed and large true metacentric) were identified. The interspecific nature of the hybrids was further confirmed by the presence of both rat and mouse adenosine deaminase and superoxide dismutase isozymes. Using specific antisera and indirect immunoperoxidase staining, both hybrid clones and GH3 rat parental cells stained positively for rat GH and PRL, while the murine fibroblast parental cells were negative. Hormone production by the hybrids has been sustained for over twenty subcultures; secretion rates were initially 150 ng PRL and 321 ng GH/10(6) cells/24 h and are currently 100 ng PRL and 90 ng GH/10(6) cells/24 h. Parental GH3 rat cells secreted 720 ng PRL and 660 ng GH/10(6) cells/24 h. Exposure of hybrids to KCl (50 mM) resulted in acute stimulation of rat PRL, but not rat GH release, and long-term incubation with thyrotropin-releasing hormone (TRH, 80 nM) stimulated PRL secretion. Hormone-dependent modulation of PRL secretion was transferred to the hybrid cell thus enabling the model to be used in studying regulation of PRL gene expression.
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PMID:Isolation and characterization of rat-mouse somatic cell hybrids secreting growth hormone and prolactin. 351 Aug 81

A rapid, sustained lipolytic response to growth hormone (GH; 20 microgram/ml) was observed in experiments using the perifused fat cell system. No lipolytic response to this agent was observed when fat cells were incubated by the traditional flask incubation method, although isoproterenol stimulated lipolysis in this preparation. In experiments using flask incubated fat cells, isoproterenol increased cyclic AMP content while GH had no effect. However, in the presence of theophylline, isoproterenol and GH significantly increased cyclic AMP levels. In perifused fat cells, both isoproterenol and GH significantly increased cyclic AMP levels in the absence of theophylline. The presence of adenosine deaminase resulted in significant increases in the lipolytic response to isoproterenol and unmasked a lipolytic response to GH when the flask-incubated fat cell system was used. The antilipolytic action of adenosine was determined in perifused fat cells. It was found that the lipolytic response to GH was at least 10 times as sensitive to the inhibitory action of adenosine as was the lipolytic response to isoproterenol. It is concluded that the lipolytic response to GH in the flask-incubation method is prevented by the accumulation of adenosine. This rapid lipolytic response is unmasked in the perifused fat cell system because adenosine fails to accumulate as it is washed from the cell population by the constantly flowing buffer.
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PMID:Growth hormone stimulation of lipolysis and cyclic AMP levels in perifused fat cells. 625 27

Ovine growth hormone ( oGH ) was tested for its effects on lipolysis of rat and ovine adipose tissue in vitro. Ovine growth hormone at 1, 5 and 25 micrograms/ml stimulated lipolysis (P less than .05) of chopped rat adipose tissue and isolated rat adipocytes incubated in the presence of 100 mU/ml adenosine deaminase and .2 micrograms/ml dexamethasone, but had no effect on lipolysis of chopped ovine adipose tissue or isolated ovine adipocytes. Isoproterenol, a beta-adrenergic agonist, stimulated lipolysis (P less than .05) of both rat and ovine adipose tissue. Contaminants of the oGH preparation used were examined for lipolytic effects. Thyroid-stimulating hormone (TSH), luteinizing hormone (LH) and adrenocorticotropic hormone (ACTH) content in oGH were measured by radioimmunoassay. When quantities of these hormones contaminating 5 and 25 micrograms oGH were tested for lipolysis in rat adipose tissue, the TSH contamination could account for some (30%) of the lipolysis observed with oGH , while the other hormones had no effect. Also, preincubation of oGH with anti-GH, but not with anti-TSH or anti-LH, removed the principle in oGH responsible for the lipolytic effect on rat adipose tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of ovine growth hormone and other anterior pituitary hormones on lipolysis of rat and ovine adipose tissue in vitro. 633 17

The lipolytic activities of porcine pituitary fractions and purified growth hormone (GH) from human (h), porcine (p), ovine (o) and rabbit (Rb) origin as well as ovine placental lactogen (oPL), were compared to that of ACTH on rabbit adipocytes. All the GH preparations and oPL were equivalent in inhibiting the binding of labelled oGH to liver plasma membranes from pregnant rabbits. ACTH, and to a lesser extent porcine pituitary fractions and hGH, stimulated free fatty acid production by isolated adipocytes. The sensitivity of the adipocytes to these factors was increased when adenosine deaminase was added to the incubation medium. But, RbGH, pGH, oGH and oPL had no effect. We conclude that GH is not directly involved in the control of lipolysis in rabbit adipocytes and that the effect of hGH is rather due to a contamination of this preparation by other pituitary factors.
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PMID:Reevaluation of lipolytic activity of growth hormone in rabbit adipocytes. 633 44

In vitro lipolysis by chicken adipose explants was stimulated by growth hormone (GH) or glucagon. Adenosine or the adenosine agonist, N6-phenylisopropyladenosine (PIA), inhibited GH stimulated lipolysis, the effect of adenosine not being observed in the presence or adenosine deaminase. Glucagon induced lipolysis was also reduced by PIA. It is suggested that adenosine may act by Gi linked to either adenylate cyclase (for glucagon) or the signal transduction mechanism for GH. Lipolysis was not stimulated by GH in the presence of phenylephrine (alpha 1 adrenergic agonist), isoproterenol (beta adrenergic agonist), adrenaline or glucagon. Although the presence of p-amino clonidine (alpha 2 adrenergic agonist) depressed basal lipolysis, a response to GH was still present. Either glucagon or beta-adrenergic agonists (isoproterenol, adrenaline) stimulated lipolysis. In both cases, GH attenuated the lipolytic response to these hormones, which act via a cyclic adenosine monophosphate signal transduction mechanism.
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PMID:Influence of adenosine or adrenergic agonists on growth hormone stimulated lipolysis by chicken adipose tissue in vitro. 774 92

The possible modification of the in vitro lipolytic action of rat growth hormone (rGH) or a mixed beta-adrenergic agonist (metaproterenol) on rat adipose tissue after a previous acute treatment with these compounds was assessed by measuring glycerol release from adipocytes. The involvement of adenosine deaminase (ADA) and dexamethasone, was also considered. The results showed that the previous acute treatment with rGH or the beta-adrenergic agonist did not alter the in vitro rGH or metaproterenol lipolytic response. The presence of ADA at a non-lipolytic concentration per se (0.02 U/ml) potentiated the lipolytic response of both compounds. Also, the addition of non-lipolytic concentrations of dexamethasone (0.5 microM) or beta-adrenergic agonist (10(-7)M) to the incubation medium potentiated the rGH lipolytic response, while the metaproterenol-induced glycerol release was not affected by the simultaneous addition of a rGH concentration (2 x 10(-7) M) which had no lipolytic effect per se.
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PMID:Analysis of the interactions between growth hormone and metaproterenol on lipid mobilization. 860 92

Current human gene therapy relies on genetic modification of the patient's own cells. An alternate non-autologous approach is to use universal cell lines engineered to secrete therapeutic products. Protection with immuno-isolation devices would allow the same recombinant cell line to be used for different patients, thus potentially lowering the cost of treatment. The feasibility of this idea has now been demonstrated in vitro and in vivo. Recombinant gene products with potential therapeutic applications (human growth hormone, factor IX, lysosomal enzymes, adenosine deaminase) have been expressed from genetically modified cells after encapsulation with alginate-poly-L-lysine-alginate or hydroxyethyl methacrylate-methyl methacrylate. We have also demonstrated the feasibility of this idea in vivo. After intraperitoneal implantation, genetically modified mouse Ltk- fibroblasts or C2C12 myoblasts encapsulated in alginate-poly-L-lysine-alginate could deliver recombinant gene products (human growth hormone, human factor IX) to the systemic circulation of mice. The clinical efficacy of this novel approach to gene therapy has now been shown in murine models of human diseases. In the Snell dwarf mice deficient in growth hormone production, implantation of encapsulated mouse myoblasts engineered to secrete mouse growth hormone resulted in increases in body weight, length and organ sizes, some to > 25% above those of the controls. In the Gus/Gus mice suffering from the lysosomal storage disease mucopolysaccharidosis type VII due to deficient beta-glucuronidase, implantation of encapsulated mouse fibroblasts engineered to secrete mouse beta-glucuronidase resulted in delivery of normal levels of the enzyme in the plasma and significant correction of the organ histopathology. Hence, delivery of recombinant gene products through bioartificial devices appears to be a promising strategy for the treatment of genetic diseases.
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PMID:Microcapsules as bio-organs for somatic gene therapy. 961 35

Direct effects of recombinant ovine leptin on adipose metabolism in sheep were investigated. Lipolytic and lipogenic rates were assessed following preincubation of subcutaneous adipose tissue explants with recombinant ovine leptin. Leptin had no consistent effect on the basal (unstimulated) lipolytic rate in adipose tissue from wethers. Lipolytic rate measured in the presence of combinations of adenosine deaminase, isoprenaline, and N6-phenylisopropyl adenosine was unaffected by pretreatment with leptin. In lactating ewes, there was no relationship between increasing concentrations of leptin and basal lipolytic rate. Leptin had no effect on basal (unstimulated) lipogenesis, or on insulin-stimulation or growth hormone inhibition of lipogenesis in adipose tissue from wethers. Lipogenesis in adipose tissue from lactating ewes was also unaffected by preincubation with leptin; however, at supraphysiological concentrations of leptin, there was a small reduction in the rate of insulin-stimulated lipogenesis. Leptin failed to induce phosphorylation of the signal transducers and activators of transcription, STAT 3 and STAT 5, in sheep adipocytes. These results suggest that leptin does not have a direct physiological effect on subcutaneous adipose tissue metabolism in sheep.
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PMID:Effects of recombinant ovine leptin on in vitro lipolysis and lipogenesis in subcutaneous adipose tissue from lactating and nonlactating sheep. 1121 54


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