Disease relevance of PAOX

• The human colon carcinoma-derived cell line CaCo-2 was used as a model to study the toxicity of N(1) OSSpm as a function of polyamine oxidase (PAO) activity and differentiation [1].
• Inhibition of polyamine oxidase enhances the cytotoxicity of polyamine oxidase substrates. A model study with N(1)-(n-octanesulfonyl)spermine and human colon cancer cells [1].
• Transfection of A549 human lung cancer cells with an hPAO-expressing plasmid leads to a profound decrease in sensitivity to those analogues which act as substrates, confirming its potential to alter drug response [2].
• Polyamine oxidase and acrolein as novel biochemical markers for diagnosis of cerebral stroke [3].
• Serum polyamine-oxidase activity in spontaneous abortion [4].

Psychiatry related information on PAOX

• Activity levels of platelet monoamine oxidase (MAO), plasma amine oxidase (PAO), erythrocyte catechol-o-methyltransferase, and dopamine-beta-hydroxylase were measured in 24 drug-free patients with Tourette's syndrome (TS) and in 24 normal control subjects matched for age and sex [5].
• Neuropsychological tests and [99mTc]-HM PAO SPECT in the diagnosis of Alzheimer's dementia [6].

High impact information on PAOX

• The mechanism of spermine-mediated cytokine suppression was posttranscriptional and independent of polyamine oxidase activity [7].
• This effect of PAO inhibition is monocyte mediated [8].
• Cerebral ischemia stimulates increased activity of polyamine oxidase, a ubiquitous enzyme that catabolizes polyamines to produce 3-aminopropanal [9].
• In contrast, the coaddition of catalase or PAO inhibitor has no effect on reducing HMW DNA fragmentation induced by N1-ethyl-N11-[(cycloheptyl)methyl]-4,8,-diazaundecane, which does not induce SSAT and does not deplete intracellular polyamines [10].
• The catalysis of polyamines by the SSAT/polyamine oxidase (PAO) pathway produces H2O2 as one product, suggesting that PCD produced by CPENSpm may be, in part, due to oxidative stress as a result of H2O2 production [10].

Chemical compound and disease context of PAOX

• These data suggest that MDL 72527 has a target unrelated to PAO, which is responsible for the enhancement of N(1)OSSpm (and spermine) toxicity [11].
• Effect of the polyamine oxidase inactivator MDL 72527 on N(1)-(n-octanesulfonyl)spermine toxicity [11].
• In order to investigate the basis of functional diversity among the pyridine nucleotide-oxidoreductases the gor gene from Pseudomonas aeruginosa PAO, which encodes glutathione reductase, was analysed [12].
• During the postoperative period, after twenty days, six months and one year, respectively, we analyzed the following data: body weight, signs of gastroesophageal reflux, subjective discomfort, early postoperative complications, gastroduodenoscopic findings, basal acid output (BAO), and maximal acid output stimulated by pentagastrin (PAO) [13].
• The role of Pseudomonas aeruginosa exotoxin A was studied in acute and chronic pyelonephritis models employing an exotoxin A-producing strain PAO, and its toxin deficient mutant PAOT1 [14].

Biological context of PAOX

• It has been shown that in the presence of certain aldehydes, the substrate specificity of PAO and the kinetics of the reaction are changed to favor spermine and spermidine as substrates [15].
• Potentiation of apple procyanidin-triggered apoptosis by the polyamine oxidase inactivator MDL 72527 in human colon cancer-derived metastatic cells [16].
• The recent cloning of the mammalian gene coding for N(1)-acetylpolyamine oxidase (PAO) provides the opportunity to directly examine the role of human PAO (hPAO) in polyamine homeostasis as well as its potential role in determining cellular response to antitumor polyamine analogues [2].
• We found that polyamine oxidase activity suppresses both anti-CD3-induced IL-2 production and protein tyrosine phosphorylation [17].
• In accordance with the oxidation dependence of this suppressive mechanism, N-acetylcysteine (NAC; an antioxidant) significantly reversed the polyamine oxidase effects on lymphokine production and signal transduction [17].

Anatomical context of PAOX

• Polyamine biosynthesis by mononuclear cells (MNC) appears to regulate T cell activity since 1) inhibition of polyamine biosynthesis increases IL-2 production and 2) H2O2 (a product of polyamine oxidase, PAO), suppresses lymphocyte proliferation [18].
• Products of polyamine oxidase activity, at micromolar levels and during a period of 2 to 3 days, down-regulate IL-2 mRNA levels and activity in human lymphocytes [17].
• Immunogold ultrastructural analysis in epidermal cells revealed the association of PAO with the secretory pathway and the cell walls [19].
• The PAO inhibitor, in combination with CHENSpm, caused a significant increase in intracellular CHENSpm levels and increased growth inhibition and cell damage in CHO cells but not in HCT116 cells [20].
• This cell line-specific difference in CHENSpm toxicity was not attributable to differences in analogue uptake, because intracellular levels of the drug were similar in CHO and HCT116 cells treated with equivalent concentrations of CHENSpm in the presence of MDL 72,527, a specific inhibitor of PAO [20].

Associations of PAOX with chemical compounds

• PAO displayed the same stereospecificity with both singly and doubly alpha-methylated spermine derivatives when supplemented with the same aldehydes [15].
• DFMO treatment for 12 h caused reductions of only 11 and 4% in SSAT and PAO, respectively, despite polyamine reductions of 94, 96, and 90% for putrescine, spermidine, and spermine, respectively [21].
• FAD-dependent polyamine oxidase (PAO; EC 1.5.3.11) is one of the key enzymes in the catabolism of polyamines spermidine and spermine [15].
• Here we report that PAO, which normally metabolizes achiral substrates, oxidized (R)-isomer of 1-amino-8-acetamido-5-azanonane and N1-acetylspermidine as efficiently while (S)-1-amino-8-acetamido-5-azanonane was a much less preferred substrate [15].
• PAO supplemented with benzaldehyde predominantly catalyzed the cleavage of (R)-isomer of alpha-methylspermidine, whereas in the presence of pyridoxal the (S)-alpha-methylspermidine was preferred [15].

Analytical, diagnostic and therapeutic context of PAOX

• To test this, the responses of the polyamine catabolic enzymes spermidine/spermine acetyltransferase (SSAT) and polyamine oxidase (PAO) were determined using a new high-performance liquid chromatography assay to measure the products of these enzymes [21].
• In Northern blot analysis, PAO mRNA was much less abundant in HEK-293 cells than SMO or SSAT mRNA, and all three were differentially induced in a similar manner by selected polyamine analogues [22].
• The monoclonal antibody and the IgE from the purified fraction were tested on two glycoproteins, polyamine oxidase and ascorbate oxidase, adsorbed on the ELISA plates [23].
• Crystallization and preliminary X-ray analysis of polyamine oxidase from Zea mays L [24].
• The implication of these observations is that immunosuppression is mediated by oxidative products issued from an interaction between polyamine and polyamine oxidase in the syncytiotrophoblast cytosol [25].

References