Disease relevance of Dao1

• METHODS: In HTC rat hepatoma cells, oxidative stress was produced by exposure to H(2)O(2) or D-alanine plus D-amino acid oxidase (40 U/mL) [1].
• A clonal line of 9L glioma cells stably transfected with this construct (9Ldaao17) was found to synthesize active R. gracilis DAAO [2].
• Induction of cytotoxic oxidative stress by D-alanine in brain tumor cells expressing Rhodotorula gracilis D-amino acid oxidase: a cancer gene therapy strategy [2].
• However, injection of d-propargylglycine into LEA/SENDAI rats did not cause any glucosuria or polyuria, indicating that D-amino-acid oxidase is definitely not functional in these rats [3].
• Application of D-amino acid oxidase, an enzyme that degrades D-serine, markedly inhibited neuronal damage by NMDA and simulated ischemia, which was reversed by addition of excess D-serine or glycine [4].

High impact information on Dao1

• This study was designed to determine whether a provocative test for increasing the level of plasma DAO activity by heparin administration could be used to monitor the extent and severity of acute, severe, small intestinal mucosal injury [5].
• Diamine oxidase (DAO; EC 1.4.3.6) is an enzyme found in high activity in the mature cells of the upper villus of rat small intestinal mucosa and in very much lower activity in all other tissues in the nonpregnant rat [5].
• Po were labeled cytochemically for either catalase, which stains them all uniformly, or for D-amino acid oxidase (DAA-OX), which gives a heterogeneous reaction with lightly and darkly stained PO [6].
• The interconnections between Po with differing DAA-OX activities suggest that they originate from the same parent organelle [6].
• Peroxisomal enzyme activities change to approximately 165%, 50%, 30%, and 0% of the controls for catalase, urate oxidase, L-alpha-hydroxy acid oxidase, and D-amino acid oxidase, respectively [7].

Chemical compound and disease context of Dao1

• The metabolism of D-serine by D-amino acid oxidase (D-AAO) may be involved in the mechanism of toxicity [8].
• We suggest that DAO, through elimination of histamine from the bloodstream, is important for the recovery from histamine-induced hypotension, and that the duration of histamine-induced pressure drop is influenced by formation of nitric oxide [9].
• Therefore, the protective effect of Oxo on 5-FU-induced GI tract toxicity was clarified by measuring plasma DAO activity in rats [10].
• 1) Vitamin B2-butyrate (100 mg/kg) and nicomol (lg/Kg) increased carnitine acetyltransferase and D-amino acid oxidase activities, respectively, while these drugs had no influence on body weight, liver weight, serum and liver triglyceride, and serum and liver cholesterol levels [11].

Biological context of Dao1

• Role of renal D-amino-acid oxidase in pharmacokinetics of D-leucine [12].
• These results demonstrate that expression of R. gracilis DAAO in tumor cells confers chemosensitivity to D-alanine that could be exploited as a novel cancer gene therapy paradigm [2].
• Hydrogen peroxide (H2O2) is a reactive oxygen species (ROS) generated in the stereoselective deamination of D-amino acids catalyzed by D-amino acid oxidase (DAAO) [2].
• Heparin releases diamine oxidase (DAO) of enterocytic origin from binding sites located on small bowel microvascular endothelium [13].
• Gene expression of D-amino acid oxidase in cultured rat astrocytes: regional and cell type specific expression [14].

Anatomical context of Dao1

• The decrease in plasma PHD activity closely reflected the length of intestinal mucosa injured (n = 128, r = 0.86, P less than 0.001), and it was much more sensitive (threshold limit of detection = 13% of total length, range = 67 U/ml for 100% length of injury) than unstimulated basal levels of plasma DAO (threshold = 40%, range = 2.1 U/ml) [5].
• Whereas all segments of this reticulum stained homogeneously for catalase, they exhibited a marked difference in the intensity of the DAA-OX reaction [6].
• Ornithine decarboxylase and DAO were assayed in the proximal and distal small bowel mucosa of 55 rats, starved for four days and then refed [15].
• These data confirm the prominence of ODC in the replication processes and suggest that intestinal DAO may not play a major role in enterocyte replication [15].
• These observations demonstrate the capability of mammalian peroxisomes to oxidize pipecolic acid and suggest that the absence or deficiency of peroxisomal D-amino acid oxidase may be implicated in the pathogenesis of hyperpipecolatemia in Zellweger's CHRS [16].

Associations of Dao1 with chemical compounds

• This drop of D-serine in adult stages corresponded to an increasing expression of D-AAO at mature stages [17].
• Application of d-amino acid oxidase, which degrades d-serine, reduced the magnitude of NMDA receptor-mediated currents, raising the possibility that endogenous d-serine serves as a ligand for setting the sensitivity of NMDA receptors under physiological conditions [18].
• Localizations of D-serine immunoreactivity correlate closely with those of D-serine binding to the glycine modulatory site of the N-methyl-D-aspartate (NMDA) receptor as visualized by autoradiography and are inversely correlated to the presence of D-amino acid oxidase [19].
• A commercially available crystalline suspension of D-amino acid oxidase from porcine kidney also oxidized the pipecolic acid with the following rates 54:36:1 respectively for D-:,D,L-:L-isomers [16].
• To study the presence of diamine oxidase (DAO) activity in any tissue with putrescine as the substrate, it is necessary to use inhibitors to block all pathways that could further metabolize gamma-aminobutyraldehyde, which is the product of enzyme reaction [20].

Other interactions of Dao1

• In this study we show that D-serine is present in the VN and we analyzed its distribution and the levels of expression of serine racemase and D-amino acid oxidase (D-AAO) at different stages of postnatal (P) development [17].
• In the brain of adult zitter rats which show degenerative changes, significantly enhanced activities of SOD and D-AAO were obtained, whereas activity of catalase was lower than that of the SD/J rats [21].
• We now show that selective degradation of d-serine with D-amino acid oxidase greatly attenuates NMDA receptor-mediated neurotransmission as assessed by using whole-cell patch-clamp recordings or indirectly by using biochemical assays of the sequelae of NMDA receptor-mediated calcium flux [22].
• The activities of the peroxisomal H2O2-producing oxidases, D-amino acid oxidase and acyl-coenzyme A oxidase, and of the extraperoxisomal superoxide dismutase are decreased in renal homogenate [23].
• Acyl-CoA oxidase, D-amino acid oxidase, L-pipecolic acid oxidase, and dihydroxyacetone phosphate acyltransferase activities and activities for the oxidation of very long chain fatty acid (lignoceric acid) were almost exclusively associated with catalase activity (a marker enzyme for peroxisomes) in the gradient [24].

Analytical, diagnostic and therapeutic context of Dao1

• We studied the distribution of D-serine and its synthesizing and degrading enzymes, serine racemase and d-amino acid oxidase in the rat vestibular sensory epithelium using immunocytochemistry [25].
• Expression of DAO mRNA in the antrum is demonstrated by reverse transcriptase polymerase chain reaction (RT-PCR) [26].
• Western blotting analysis of antrum and colon demonstrate that both antisera react with a single band of 85 kD, consistent with the predicted molecular weight of DAO [26].
• The localization of D-amino acid oxidase in this small area of the peroxisomal matrix was confirmed by immunoelectron microscopy on freeze-substituted tissues processed without chemical fixation [27].
• Semi-thin sections were stained for DAO by the immunoenzyme technique after removal of epoxy resin for LM, and ultra-thin sections of Lowicryl-embedded material were labeled for DAO by the protein A-gold technique for EM [28].

References