Disease relevance of Ada

• These results should facilitate the development of gene therapy protocols for the treatment of severe combined immunodeficiency caused by a lack of functional ADA [1].
• Bradycardia and vasodilation in response to AR agonism (2-chloroadenosine) were unaltered by ADA deficiency, while A1AR deficiency eliminated the heart rate response [2].
• These data suggest that disturbances in purinergic signaling mediate the lung inflammation and damage seen in ADA-deficient mice [3].
• Lowering adenosine and 2'-deoxyadenosine levels using ADA enzyme therapy decreased the pulmonary eosinophilia and resolved many of the lung histopathologies [3].
• Metabolic consequences of adenosine deaminase deficiency in mice are associated with defects in alveogenesis, pulmonary inflammation, and airway obstruction [3].

Psychiatry related information on Ada

• Agents which inhibit the transport of adenosine (dipyridamole, dilazep, papaverine) depressed locomotor activity, as did erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA, an inhibitor of adenosine deaminase [4].

High impact information on Ada

• Base conversion in the channel-coding region of GluR-B directed by base paired sequences may be executed by a ubiquitous nuclear adenosine deaminase specific for double-stranded RNA [5].
• The members of the ADAR (adenosine deaminase acting on RNA) gene family are involved in site-selective RNA editing that changes adenosine residues of target substrate RNAs to inosine [6].
• The crystal structure of a murine adenosine deaminase complexed with 6-hydroxyl-1,6-dihydropurine ribonucleoside, a nearly ideal transition-state analog, has been determined and refined at 2.4 angstrom resolution [7].
• Adenosine deaminase (ADA) is a purine catabolic enzyme that manages levels of the biologically active purines adenosine and 2'-deoxyadenosine in tissues and cells [3].
• The inflammatory changes found in the lungs of ADA-deficient mice included an accumulation of activated alveolar macrophages and eosinophils [3].

Chemical compound and disease context of Ada

• In addition, genetically restoring ADA to the forestomach of otherwise ADA-deficient mice prevented adenine metabolic disturbances as well as lung inflammation and damage [3].
• The simultaneous administration of 3'-deoxyadenosine N1-oxide (3'-dANO) and the adenosine deaminase inhibitors erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) or 2'-deoxycoformycin (2'-dCF) to mice bearing Ehrlich ascites tumor cells resistant to 3'-dANO resulted in 80%-90% inhibition of tumor growth in vivo [8].
• Synergistic effect of 3'-deoxyadenosine N1-oxide and adenosine deaminase inhibitors on growth of Ehrlich ascites tumor cells in vivo [8].
• Deoxyadenosine, a cytotoxic purine nucleoside, is excreted in large amounts by patients with severe combined immunodeficiency disease associated with deficiency of adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4) [9].
• 2'-Deoxycoformycin (2'-dCF), a potent inhibitor of adenosine deaminase, was tested in combination with 9-beta-D-arabinofuranosyladenine (ara-A) and 9-beta-D-arabinofuranosyladenine 5'-formate for cytotoxic activity against mouse leukemia L1210 in culture [10].

Biological context of Ada

• Regulation of murine Ada gene expression in the placenta by transcription factor RUNX1 [11].
• A 770bp fragment of the mouse Ada 5' flanking region is capable of directing trophoblast cell-specific expression in a transgenic model system [11].
• Ada is highly expressed in trophoblast cells of the placenta and is critical for embryo development [11].
• The findings reported here indicate that the RUNX1 transcription factor plays a significant role in regulating Ada gene expression in the trophoblast cell lineage [11].
• Adenosine deaminase, Ada, is in mouse chromosome 2H3, and is not allelic with wasted, wst [12].

Anatomical context of Ada

• Factors affecting the transduction of pluripotent hematopoietic stem cells: long-term expression of a human adenosine deaminase gene in mice [1].
• An amphotropic retroviral vector, LgAL(delta Mo + PyF101) containing a human adenosine deaminase (ADA) cDNA was used to optimize procedures for the lasting genetic modification of the hematopoietic system of mice [1].
• In spleen T lymphocytes, ADA and deoxyCRK activities were lower and PNP activity was about 2.5-fold higher than in the thymocytes [13].
• In the adult mouse, Ada is highly expressed in the terminally differentiated epithelial layer of upper gastrointestinal tract tissues [14].
• Neither ADA nor DMPX affected leukocyte accumulation in the inflamed pouches of animals treated with either saline or the potent antiinflammatory steroid dexamethasone [15].

Associations of Ada with chemical compounds

• Analysis of embryo cultures suggests that AP-2 gamma is also implicated in the regulation of the adenosine deaminase (ADA) gene, a gene involved in purine metabolism found expressed at the maternal-fetal interface [16].
• Elimination of endogenous adenosine with adenosine deaminase (ADA) markedly suppressed IL-2-dependent proliferation of these cells [17].
• A23187 (100 nM) and phorbol 12,13 dibutyrate (10 nM), but not 4 alpha-phorbol (10 nM), were able to restore IL-2-dependent CTLL-2 proliferation in the presence of ADA [17].
• Adenosine efflux increased 10- to 20-fold with ADA deficiency (at the expense of inosine) [2].
• In the presence of 10 microM erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) to block intracellular adenosine deaminase (ADA) activity, 2'-deoxyformycin A and dAdo both gave IC50's of 5-10 microM [18].

Regulatory relationships of Ada

• Adenosine kinase inhibition promotes survival of fetal adenosine deaminase-deficient thymocytes by blocking dATP accumulation [19].
• Deletion of ADA also enhanced tolerance in A1AR deficient hearts, though effects on diastolic pressure were eliminated [2].
• Transcription factor AP-2gamma regulates murine adenosine deaminase gene expression during placental development [20].

Other interactions of Ada

• From the current data Ada can be taken as the proximal, and Ra as the distal gene marker of the imprinting region on the linkage map [21].
• Chromosomal mapping of enzyme loci in the domestic cat: GSR to C2, ADA and ITPA to A3, and LDHA-ACP2 to D1 [22].
• Deletion of ADA improved outcome from 25 min ischaemia, reducing ventricular diastolic pressure (by 45%; 21+/-4 vs. 38+/-3mm Hg) and lactate dehydrogenase (LDH) efflux (by 40%; 0.12+/-0.01 vs. 0.21+/-0.02 U/g/min ischaemia), and enhancing pressure development (by 35%; 89+/-6 vs. 66+/-5mm Hg) [2].
• Fibroblasts were engineered to release adenosine by inactivating the adenosine-metabolizing enzymes adenosine kinase and adenosine deaminase [23].
• In cotransfection assays, increased mGPBP expression transactivated the murine Ada gene's promoter [24].

Analytical, diagnostic and therapeutic context of Ada

• METHODS: Normoxic function and responses to 20 or 25 min ischaemia and 45 min reperfusion were studied in isolated hearts from wild-type mice and from mice deficient in ADA and/or A1ARs [2].
• The adenosine deaminase locus (Ada) in the mouse has been localized by in situ hybridization to band 2H3 [12].
• Molecular cloning of the murine adenosine deaminase gene from a genetically enriched source: identification and characterization of the promoter region [25].
• Further differentiation of murine double-positive thymocytes is inhibited in adenosine deaminase-deficient murine fetal thymic organ culture [26].
• Adenosine deaminase-deficient mice generated using a two-stage genetic engineering strategy exhibit a combined immunodeficiency [27].

References