Effects of amine oxidases in allergic and histamine-mediated conditions.

This review provides an update on histamine, on diamine oxidase (DAO) and on their implications in allergy and various conditions or affections, such as food histaminosis, ischemia and inflammatory bowel diseases (IBD). The review also presents, in brief, patent coverage on therapies for allergy and IBD with the focus on histamine-related treatments.

Zymographic assay of oxidases using peroxidase or hemin entrapped in polyacrylamide gel.

This chapter describes a zymographic assay of oxidases which is based on a coupled peroxidase or hemin reaction. The enzymatic activity of oxidases (i.e.

Carboxymethyl starch: Chitosan monolithic matrices containing diamine oxidase and catalase for intestinal delivery.

The capacity of carboxymethyl starch (CMS):Chitosan monolithic tablets to protect diamine oxidase and/or catalase therapeutic enzymes against simulated gastric fluid (SGF) and to control their delivery in simulated intestinal fluid (SIF) was investigated. Enzyme formulations loaded with grass pea seedlings diamine oxidase (PSDAO) vegetal extract, catalase, or PSDAO associated to catalase, were obtained by direct compression. The CMS:Chitosan (1:1) matrix afforded a good gastric protection to PSDAO and to catalase, when each enzyme was formulated separately.

Lathyrus cicera copper amine oxidase reactions with tryptamine.

Lathyrus cicera copper amine oxidase (LCAO) rapidly formed the typical Cu(I)-TPQ semiquinone UV-visible spectrum, identical to that formed by other substrates, upon O(2) exhaustion by turnover with excess tryptamine. A new band at 630 nm formed more slowly, with intensity dependent on aldehyde and H(2)O(2) concentrations. On prolonged incubation, all bands decayed in parallel, together with loss of enzymatic activity.

Zymographic assay of plant diamine oxidase on entrapped peroxidase polyacrylamide gel electrophoresis. A study of stability to proteolysis.

A zymographic assay of diamine oxidase (DAO, histaminase, EC 1.4.3.

Pea seedling histaminase as a novel therapeutic approach to anaphylactic and inflammatory disorders. A plant histaminase in allergic asthma and ischemic shock.

Amine oxidases (AOs) are ubiquitous enzymes involved in the metabolism of biogenic amines. Copper AOs (Cu-AOs) catalyze the oxidative deamination of primary amine groups of several biogenic amines, such as putrescine, cadaverine, and histamine. In the present review, the effects of a plant amine oxidase (Cu-AO, histaminase, EC1.

Inducible expression of maize polyamine oxidase in the nucleus of MCF-7 human breast cancer cells confers sensitivity to etoposide.

In this study, polyamine oxidase from maize (MPAO), which is involved in the terminal catabolism of spermidine and spermine to produce an aminoaldehyde, 1,3-diaminopropane and H(2)O(2), has been conditionally expressed at high levels in the nucleus of MCF-7 human breast cancer cells, with the aim to interfere with polyamine homeostasis and cell proliferation. Recombinant MPAO expression induced accumulation of a high amount of 1,3-diaminopropane, an increase of putrescine levels and no alteration in the cellular content of spermine and spermidine. Furthermore, recombinant MPAO expression did not interfere with cell growth of MCF-7 cells under normal conditions but it did confer higher growth sensitivity to etoposide, a DNA topoisomerase II inhibitor widely used as antineoplastic drug.

Catalase takes part in rat liver mitochondria oxidative stress defense.

Highly purified rat liver mitochondria (RLM) when exposed to tert-butylhydroperoxide undergo matrix swelling, membrane potential collapse, and oxidation of glutathione and pyridine nucleotides, all events attributable to the induction of mitochondrial permeability transition. Instead, RLM, if treated with the same or higher amounts of H2O2 or tyramine, are insensitive or only partially sensitive, respectively, to mitochondrial permeability transition. In addition, the block of respiration by antimycin A added to RLM respiring in state 4 conditions, or the addition of H2O2, results in O2 generation, which is blocked by the catalase inhibitors aminotriazole or KCN.

Substrate specificity of copper-containing plant amine oxidases.

The steady-state kinetic parameters of the amine oxidases purified from Lathyrus cicera (LCAO) and Pisum sativum (PSAO) seedling were measured on a series of common substrates, previously tested on bovine serum amine oxidase (BSAO). LCAO, as PSAO, was substantially more reactive than BSAO with aliphatic diamines and histamine. The k(cat) and k(cat)/Km for putrescine were four and six order of magnitude higher, respectively.

Beneficial effects of a plant histaminase in a rat model of splanchnic artery occlusion and reperfusion.

Splanchnic artery occlusion (SAO) followed by reperfusion causes endothelial injury and inflammation which contribute to the pathophysiology of shock. We investigated the effects of pea seedling (Latyrus cicera) histaminase, known to afford protection against the deleterious effects of cardiac ischemia/reperfusion, given to rats subjected to SAO/reperfusion-induced splanchnic injury. Histaminase (80 IU kg, 15 min before reperfusion) significantly reduced the drop of blood pressure and high mortality rate caused by SAO/reperfusion.

Amine oxidases in apoptosis and cancer.

Amine oxidases, the major enzymes of biogenic amines metabolism, are considered to be biological regulators, especially for cell growth and differentiation. A primary involvement of amine oxidases in cancer growth inhibition and progression, especially by means of aldehydes, H(2)O(2) and other reactive oxygen species, the amine oxidase-mediated products of biogenic amines oxidation, has been demonstrated. Amine oxidases are involved in cancer growth inhibition because of the higher content in tumour cells of biogenic amines in comparison to normal cells.

Effect of a plant histaminase on asthmalike reaction induced by inhaled antigen in sensitized guinea pig.

This study evaluates the effects of a copper amine oxidase (histaminase) purified from the pea seedling as a free or immobilized enzyme on asthmalike reactions to inhaled antigen in actively sensitized guinea pig in vivo. Male albino guinea pigs, sensitized with ovalbumin, were challenged with the antigen given by aerosol; free histaminase or CNBr-Sepharose immobilized histaminase was given intraperitoneally (20 microg, 3 or 24 h before antigen challenge) or by aerosol (4 microg, 30 min before or during ovalbumin aerosol). The following parameters were examined: latency time for the onset of respiratory abnormalities, cough severity score, and occurrence and duration of dyspnea.

Interaction of biologically active amines with mitochondria and their role in the mitochondrial-mediated pathway of apoptosis.

The natural polyamines spermine, spermidine and putrescine, polycationic molecules at physiological pH, interact with mitochondrial membranes at two specific binding sites exhibiting low affinity and high binding capacity. This binding represents the first step in the electrophoretic mechanism of polyamine transport into mitochondria. Spermine accumulated into the mitochondrial matrix is able to flow out by an electroneutral mechanism.

Biogenic amines and apoptosis: minireview article.

The programmed cell death is a very complex mechanism involving many factors, among them the intracellular concentration of biogenic amines (BA) appears to be important for apoptosis triggering. The mitochondrial damage is imputable to hydrogen peroxide and aldehydes, produced by amine oxidases (AO)-mediated oxidation of BA. On the other hands, the apoptosis protection observed by high BA concentration appears to be related to their scavenger effect of ROS and/or their interaction with membrane pores.

Synthesis and selective inhibitory activity of 1-acetyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazole derivatives against monoamine oxidase.

A novel series of 1-acetyl-3-(4-hydroxy- and 2,4-dihydroxyphenyl)-5-phenyl-4,5-dihydro-(1H)-pyrazole derivatives 1-12 have been synthesized and investigated for the ability to selectively inhibit the activity of the A and B isoforms of monoamine oxidase (MAO). The new synthesized compounds 1-12 proved to be more reversible, potent, and selective inhibitors of MAO-A than of MAO-B. Knowing that stereochemistry may be an important modulator of biological activity, we performed the semipreparative chromatographic enantioseparation of the most potent, selective, and chiral compounds, 6 and 11.

Some new functions of amine oxidases.

Two contrasting topics are examined in this account: the protective actions of amine oxidases (AOs) resulting from the elimination and/or modulation of the levels of polyamines and some biogenic amines, such as histamine, in anaphylactic shock and the cell damaging effect of AOs catabolic products. Other functions of the plasma copper-containing amine oxidase are considered; namely the modification of some proteins by oxidation of their free amino groups, the auto-regulation of the catalytic activity of AOs, the protective effect against free radicals, and the regulation of K(+)-channels.

Amine oxidases and tumors.

The physiological function in living organisms of amine oxidases, is not completely established but is certainly related to the biogenic amines metabolism and therefore involved in essential processes such as the cell growth and differentiation. A correlation between degree of tumor malignancy and level of AO activity has been reported. The catalytic products of oxidative deamination of amines (hydrogen peroxide and aminoaldehyde) exert a cytotoxic effect and are considered cell growth inhibitors.

Inactivation of copper-containing amine oxidases by turnover products.

For bovine serum amine oxidase, two different mechanisms of substrate-induced inactivation have been proposed. One consists of a slow oxidation by H2O2 of a conserved residue in the reduced enzyme after the fast turnover phase [Pietrangeli, P., Nocera, S.

L-Deprenyl as an inhibitor of menadione-induced permeability transition in liver mitochondria.

L-Deprenyl, an inhibitor of mitochondrial monoamine oxidase B (MAO B), inhibits the swelling of liver mitochondria induced by the pro-oxidant 2-methyl-1,4-naphtoquinone with a K(i) dependent on quinone concentration. L-Deprenyl also inhibits the collapse of membrane potential, cation efflux, pyridine nucleotide oxidation and cytochrome c release, all events which accompany the osmotic change and are typical of membrane permeability transition induction, thus emphasizing the inhibitory effect of the drug on this phenomenon. Results show that this inhibition is not due to the effect of L-deprenyl on monoamine oxidase activity but is most likely due to a direct interaction of the drug with the pore forming structures.

Protective effects of a plant histaminase in myocardial ischaemia and reperfusion injury in vivo.

Grass pea seedling histaminase (a copper-diamine oxidase) was found to exert a significant cardioprotection against post-ischaemic reperfusion damage. Electrocardiogram (ECG) recordings from the rats subjected in vivo to ischaemia and reperfusion showed ventricular tachycardia (VT) and ventricular fibrillations (VF) occurring in 9 out of 12 untreated rats whereas no ventricular arrhythmias were found under histaminase (80U/kg body weight) treatment (n=16 rats). Computer-assisted morphometry of the ischaemic reperfused hearts stained with nitroblue tetrazolium showed the extension of damaged myocardium (area at risk and infarct size) significantly reduced in rats treated with histaminase, in comparison with the non-treated rats, whereas no protection was found with the semicarbazide inactivated histaminase.

Is the catalytic mechanism of bacteria, plant, and mammal copper-TPQ amine oxidases identical?

This short review is mostly concerned with the work carried out in Rome on the copper amine oxidase from bovine serum (BSAO). The first target was the copper oxidation state and its relationship with the organic cofactor. It was found that copper is not reduced on reaction with amines under anaerobic conditions or along the catalytic cycle and that it is not within bonding distance of the quinone cofactor.

New perspectives on the role of amine oxidases in physiopathology.

In the paper here presented we summarize some results obtained in our laboratory in the last few years on new structural and functional aspects of some amine oxidases (AOs), which have to be taken into consideration in defining new strategies of controlling the cellular physiopathology. In particular, the ability of Cu-AO purified from vegetal sources or from bovine serum to bind different cellular targets inducing in them conformational as well as chemical modifications are described and the consequences of this interaction on cellular functions are discussed. This is the case of the protective effect of Cu-AO against the damage induced by free radicals, cell enrichment with Cu-AO, induction of cataract and the leukocyte-endothelia interaction.

Inhibition of amine oxidases activity by 1-acetyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazole derivatives.

A novel series of 1-acetyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazole derivatives have been synthesised and investigated for the ability to inhibit selectively monoamine oxidases, swine kidney oxidase, and bovine serum amine oxidase. The newly synthesised compounds 1-6 proved to be reversible and non-competitive inhibitors of all types of the assayed amine oxidases. Compounds inhibit monoamine oxidases potently, displaying low I(50) values of particular interest.

A plant histaminase modulates cardiac anaphylactic response in guinea pig.

The effect of a copper amine oxidase (histaminase) purified from the pea seedling as free or immobilized enzyme on the response to specific antigen was studied in isolated hearts from actively sensitized guinea pigs. In vitro challenge with the specific antigen of hearts from actively sensitized animals evokes a positive inotropic and chronotropic effect, a coronary constriction, followed by dilation and an increase in the amount of histamine and nitrites, the oxidation product of nitric oxide, in the perfusates. In the presence of both forms of histaminases, the positive inotropic and chronotropic responses as well as the coronary constriction and the release of histamine were fully blocked.

Tyramine and monoamine oxidase inhibitors as modulators of the mitochondrial membrane permeability transition.

Incubation of rat liver mitochondria with 100-500 mM tyramine, a substrate for monoamine oxidases A and B (MAOs), in the presence of 30 mM Ca2+ induces matrix swelling, accompanied by collapse of membrane potential, efflux of endogenous Mg2+ and accumulated Ca2+ and oxidation of endogenous pyridine nucleotides. These effects are completely abolished in the presence of cyclosporin A, ADP, dithioerythritol and N-ethylmaleimide, thus confirming the induction of the mitochondrial membrane permeability transition (MPT). The observed partial protective effect exerted by catalase indicates the involvement of both MAO-derived hydrogen peroxide and aldehyde.