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01-06-2013 | Neurology and Preclinical Neurological Studies - Original Article

New tools for studying old questions: antibodies for human diamine oxidase

Authors: Hubert G. Schwelberger, Johannes Feurle, Gunnar Houen

Published in: Journal of Neural Transmission | Issue 6/2013

Abstract

Diamine oxidase (DAO) oxidatively deaminates histamine and other diamines. Due to the lack of antibodies for human DAO, many findings on this enzyme had not been confirmed in man. Therefore, we produced a series of monoclonal antibodies by immunizing mice with human DAO protein fragments expressed in vitro. Five different monoclonal antibodies specific for human DAO were obtained that do not recognize any other human protein and can detect DAO with 100-fold greater sensitivity than the most sensitive enzymatic assays currently available. Using these antibodies allowed confirming the expression and cellular localization of DAO in various human tissues such as kidney, intestine and placenta where the presence of the enzyme had previously been deduced from activity measurement and DAO mRNA analysis. Due to the high sensitivity of the novel monoclonal antibodies, DAO was also detected at sites that previously evaded unequivocal proof of DAO enzymatic activity such as the urine. On the other hand, with these antibodies it was possible to show that DAO is normally not present in human liver and blood serum. The new monoclonal antibodies not only allow a comprehensive quantitative evaluation of the expression of DAO at the cellular level in man but will also facilitate sensitive analyses of disease-associated alterations of this enzyme.

Abella A, Garcia-Vicente S, Viguerie N, Ros-Baró A, Camps M, Palacín M, Zorzano A, Marti L (2004) Adipocytes release a soluble form of VAP-1/SSAO by a metalloprotease-dependent process and in a regulated manner. Diabetologia 47:429–438PubMedCrossRef

Barbry P, Champe M, Chassande O, Munemitsu S, Champigny G, Lingueglia E, Maes P, Frelin C, Tartar A, Ullrich A, Lazdunski M (1990) Human kidney amiloride-binding protein: cDNA structure and functional expression. Proc Natl Acad Sci USA 87:7347–7351PubMedCrossRef

Bardsley WG, Crabbe MJC, Scott IV (1974) The amine oxidases of human placenta and pregnancy plasma. Biochem J 139:169–181

Bradford MM (1976) A rapid and sensitive method for quantitation of microgram quantities of protein utilizing the principle of protein dye binding. Anal Biochem 72:248–254PubMedCrossRef

Chassande O, Renard S, Barbry P, Lazdunski M (1994) The human gene for diamine oxidase, an amiloride binding protein. Molecular cloning, sequencing, and characterization of the promoter. J Biol Chem 269:14484–14489PubMed

Hansson R, Holmberg CG, Tibbling S, Tryding N, Westling H, Wetterqvist H (1966) Heparin-induced diamine oxidase increase in human blood plasma. Acta Med Scand 180:533–536PubMedCrossRef

Houen G (1999) Mammalian Cu-containing amine oxidases (CAOs): new methods of analysis, structural relationships, and possible functions. APMIS 107(Suppl 96):1–46

Klocker J, Drasche A, Sattler J, Bodner E, Schwelberger HG (2000) Postheparin plasma diamine oxidase activity and the anticoagulant effect of heparin. Inflamm Res 49(Suppl 1):S53–S54PubMedCrossRef

Köhler G, Milstein C (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256:495–497PubMedCrossRef

Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685PubMedCrossRef

McGrath AP, Hilmer KM, Collyer CA, Shepard EM, Elmore BO, Brown DE, Dooley DM, Guss JM (2009) Structure and inhibition of human diamine oxidase. Biochemistry 48:9810–9822PubMedCrossRef

Novotny WF, Chassande O, Baker M, Lazdunski M, Barbry P (1994) Diamine oxidase is the amiloride-binding protein and is inhibited by amiloride analogues. J Biol Chem 269:9921–9925PubMed

Rajtar S, Feurle J, Schwelberger HG, Irman-Florjanc T (2006) Expression of histamine degrading enzymes in guinea pig tissues. Inflamm Res 55(Suppl 1):S61–S62PubMedCrossRef

Schwelberger HG (2004) Diamine oxidase (DAO) enzyme and gene. In: Falus A (ed) Histamine: biology and medical aspects. SpringMed Publishing, Budapest, pp 43–52

Schwelberger HG (2007) The origin of mammalian plasma amine oxidases. J Neural Transm 114:757–762PubMedCrossRef

Schwelberger HG, Bodner E (1997) Purification and characterization of diamine oxidase from porcine kidney and intestine. Biochim Biophys Acta 1340:152–164PubMedCrossRef

Schwelberger HG, Klocker J, Sattler J, Bodner E (1995) Determination of the activity of diamine oxidase in extremely small tissue samples. Inflamm Res 44(Suppl 1):S94–S95PubMedCrossRef

Schwelberger HG, Hittmair A, Kohlwein SD (1998a) Analysis of tissue and subcellular localization of mammalian diamine oxidase by confocal laser scanning fluorescence microscopy. Inflamm Res 47(Suppl 1):S60–S61PubMedCrossRef

Schwelberger HG, Stalzer B, Maier H, Bodner E (1998b) Expression and cellular localisation of diamine oxidase in the gastrointestinal tract of pigs. Inflamm Res 47(Suppl 1):S62–S63PubMedCrossRef

Stolen CM, Yegutkin GG, Kurkijärvi R, Bono P, Alitalo K, Jalkanen S (2004) Origins of serum semicarbazide-sensitive amine oxidase. Circ Res 95:50–57PubMedCrossRef

Towbin H, Staehelin T, Gordon J (1979) Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci USA 76:4350–4354PubMedCrossRef

Wilflingseder D, Sørensen BK, Houen G, Schwelberger HG (2002) Complex formation of human placental diamine oxidase. Inflamm Res 51(Suppl 1):S89–S90PubMed

Title: New tools for studying old questions: antibodies for human diamine oxidase
Authors: Hubert G. Schwelberger
Johannes Feurle
Gunnar Houen
Publication date: 01-06-2013
Publisher: Springer Vienna
Published in: Journal of Neural Transmission / Issue 6/2013
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-012-0936-2

At a glance: The STEP trials

Springer Medicine

New tools for studying old questions: antibodies for human diamine oxidase

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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