Publications

• Cloning and characterization of multiple human polyamine oxidase splice variants that code for isoenzymes with different biochemical characteristics.

  Murray-Stewart T., Wang Y., Devereux W., Casero R.A. Jr.

  The recently cloned and characterized human polyamine oxidase (PAOh1) potentially represents a new class of catabolic enzymes in the mammalian polyamine metabolic pathway capable of the efficient oxidation of polyamines. Here the discovery of three additional human PAO splice variants is reported, ... >> More

  The recently cloned and characterized human polyamine oxidase (PAOh1) potentially represents a new class of catabolic enzymes in the mammalian polyamine metabolic pathway capable of the efficient oxidation of polyamines. Here the discovery of three additional human PAO splice variants is reported, and the data support the fact that the human PAO gene codes for at least four isoenzymes, each of which exhibit distinctive biochemical characteristics, suggesting the existence of additional levels of complexity in polyamine catabolism. << Less

  Biochem. J. 368:673-677(2002) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• Yeast Fms1 is a FAD-utilizing polyamine oxidase.

  Landry J., Sternglanz R.

  In this report we show that recombinant Saccharomyces cerevisiae Fms1 protein is a polyamine oxidase that binds FAD with an FAD:Fms1 stoichiometry of 1:1. Biochemical characterization of Fms1 shows that it can oxidize spermine, N(1)-acetylspermine, N(1)-acetylspermidine, and N(8)-acetylspermidine, ... >> More

  In this report we show that recombinant Saccharomyces cerevisiae Fms1 protein is a polyamine oxidase that binds FAD with an FAD:Fms1 stoichiometry of 1:1. Biochemical characterization of Fms1 shows that it can oxidize spermine, N(1)-acetylspermine, N(1)-acetylspermidine, and N(8)-acetylspermidine, but not spermidine. The products of spermine oxidation are spermidine and 3-aminopropanal. A kinetic analysis revealed that spermine, N(1)-acetylspermine, and N(1)-acetylspermidine are oxidized with similar efficiencies, while N(8)-acetylspermidine is a poor substrate. The data support a previous report, suggesting that Fms1 is responsible for the production of beta-alanine from spermine for the synthesis of pantothenic acid. << Less

  Biochem. Biophys. Res. Commun. 303:771-776(2003) [PubMed] [EuropePMC]

  This publication is cited by 5 other entries.

• Purification and characterization of polyamine oxidase from Ascaris suum.

  Muller S., Walter R.D.

  The interconversion of polyamines in the parasite nematode Ascaris suum by a novel type of polyamine oxidase was demonstrated. The nematode enzyme was clearly distinguishable from monoamine and diamine oxidases as well as from the mammalian polyamine oxidase, as shown by the use of the specific in ... >> More

  The interconversion of polyamines in the parasite nematode Ascaris suum by a novel type of polyamine oxidase was demonstrated. The nematode enzyme was clearly distinguishable from monoamine and diamine oxidases as well as from the mammalian polyamine oxidase, as shown by the use of the specific inhibitors pargyline, aminoguanidine and MDL 72527 respectively. All three inhibitors had no effect on the parasite polyamine oxidase, and the enzyme did not accept diamines such as putrescine, cadaverine or histamine as substrates. The parasite polyamine oxidase selectively oxidizes spermine and spermidine but not N-acetylated polyamines, whereas the mammalian tissue-type polyamine oxidase shows preference for the N-acetylated polyamines. These results suggest a regulatory function of the nematode polyamine oxidase in the degradation and interconversion of polyamines in parasite nematodes. The enzyme was purified to homogeneity by gel filtration, preparative isoelectric focusing and subsequent affinity chromatography on spermine- and berenil-Sepharose 4B. With respect to reaction type, the prosthetic group FAD, the molecular mass (66 kDa) and the contents of thiol and carbonyl groups, the polyamine oxidase from A. suum is similar to the isofunctional enzyme of mammalian tissue. << Less

  Biochem J 283:75-80(1992) [PubMed] [EuropePMC]

  This publication is cited by 3 other entries.

• Bridging the gap between plant and mammalian polyamine catabolism: a novel peroxisomal polyamine oxidase responsible for a full back-conversion pathway in Arabidopsis thaliana.

  Moschou P.N., Sanmartin M., Andriopoulou A.H., Rojo E., Sanchez-Serrano J.J., Roubelakis-Angelakis K.A.

  In contrast to animals, where polyamine (PA) catabolism efficiently converts spermine (Spm) to putrescine (Put), plants have been considered to possess a PA catabolic pathway producing 1,3-diaminopropane, Delta(1)-pyrroline, the corresponding aldehyde, and hydrogen peroxide but unable to back-conv ... >> More

  In contrast to animals, where polyamine (PA) catabolism efficiently converts spermine (Spm) to putrescine (Put), plants have been considered to possess a PA catabolic pathway producing 1,3-diaminopropane, Delta(1)-pyrroline, the corresponding aldehyde, and hydrogen peroxide but unable to back-convert Spm to Put. Arabidopsis (Arabidopsis thaliana) genome contains at least five putative PA oxidase (PAO) members with yet-unknown localization and physiological role(s). AtPAO1 was recently identified as an enzyme similar to the mammalian Spm oxidase, which converts Spm to spermidine (Spd). In this work, we have performed in silico analysis of the five Arabidopsis genes and have identified PAO3 (AtPAO3) as a nontypical PAO, in terms of homology, compared to other known PAOs. We have expressed the gene AtPAO3 and have purified a protein corresponding to it using the inducible heterologous expression system of Escherichia coli. AtPAO3 catalyzed the sequential conversion/oxidation of Spm to Spd, and of Spd to Put, thus exhibiting functional homology to the mammalian PAOs. The best substrate for this pathway was Spd, whereas the N(1)-acetyl-derivatives of Spm and Spd were oxidized less efficiently. On the other hand, no activity was detected when diamines (agmatine, cadaverine, and Put) were used as substrates. Moreover, although AtPAO3 does not exhibit significant similarity to the other known PAOs, it is efficiently inhibited by guazatine, a potent PAO inhibitor. AtPAO3 contains a peroxisomal targeting motif at the C terminus, and it targets green fluorescence protein to peroxisomes when fused at the N terminus but not at the C terminus. These results reveal that AtPAO3 is a peroxisomal protein and that the C terminus of the protein contains the sorting information. The overall data reinforce the view that plants and mammals possess a similar PA oxidation system, concerning both the subcellular localization and the mode of its action. << Less

  Plant Physiol. 147:1845-1857(2008) [PubMed] [EuropePMC]

  This publication is cited by 4 other entries.

• Cloning and characterization of a human polyamine oxidase that is inducible by polyamine analogue exposure.

  Wang Y., Devereux W., Woster P.M., Murray-Stewart T., Hacker A., Casero R.A. Jr.

  Mammalian polyamine catabolism is under the control of two enzymes, spermidine/spermine N1-acetyltransferase and the flavin adenine dinucleotide-dependent polyamine oxidase (PAO). In this study, the cloning and initial characterization of human PAO is reported. A 1894-bp cDNA with an open reading ... >> More

  Mammalian polyamine catabolism is under the control of two enzymes, spermidine/spermine N1-acetyltransferase and the flavin adenine dinucleotide-dependent polyamine oxidase (PAO). In this study, the cloning and initial characterization of human PAO is reported. A 1894-bp cDNA with an open reading frame of 1668-bp codes for a protein of 555 amino acids. In vitro transcription/translation of this cDNA clone produces the expected M(r) 61,900 protein with PAO activity. The PAO activity of this clone is inhibited by MDL 72,527, a specific inhibitor of mammalian PAO. However, neither pargyline, a specific monoamine oxidase inhibitor, nor semicarbazide, a specific diamine oxidase inhibitor, inhibits the PAO activity of this clone. PAO has been referred to as being constitutively expressed. However, 24-h exposure of a non-small cell lung carcinoma cell line, NCI H157, to 10 microM of N1,N"-bis(ethyl)norspermine results in approximately 5-fold induction of PAO mRNA and a >3-fold induction of PAO activity. These results demonstrate that in at least one cell type, PAO is up-regulated in response to polyamine analogue exposure. The PAO clone described here should provide a useful tool, which will facilitate the dissection of the role of polyamine catabolism in normal growth and in response to the antitumor polyamine analogues. << Less

  Cancer Res. 61:5370-5373(2001) [PubMed] [EuropePMC]

• Identification and characterization of a novel flavin-containing spermine oxidase of mammalian cell origin.

  Vujcic S., Diegelman P., Bacchi C.J., Kramer D.L., Porter C.W.

  During polyamine catabolism, spermine and spermidine are first acetylated by spermidine/spermine N(1)-acetyltransferase (SSAT) and subsequently oxidized by polyamine oxidase (PAO) to produce spermidine and putrescine, respectively. In attempting to clone the PAO involved in this back-conversion pa ... >> More

  During polyamine catabolism, spermine and spermidine are first acetylated by spermidine/spermine N(1)-acetyltransferase (SSAT) and subsequently oxidized by polyamine oxidase (PAO) to produce spermidine and putrescine, respectively. In attempting to clone the PAO involved in this back-conversion pathway, we encountered an oxidase that preferentially cleaves spermine in the absence of prior acetylation by SSAT. A BLAST search using maize PAO sequences identified homologous mammalian cDNAs derived from human hepatoma and mouse mammary carcinoma: the encoded proteins differed by 20 amino acids. When either cDNA was transiently transfected into HEK-293 cells, intracellular spermine pools decreased by 75% while spermidine and N (1)-acetylspermidine pools increased, suggesting that spermine was selectively and directly oxidized by the enzyme. Substrate specificity using lysates of oxidase-transfected HEK-293 cells revealed that the newly identified oxidase strongly favoured spermine over N (1)-acetylspermine and that it failed to act on N (1)-acetylspermidine, spermidine or the preferred PAO substrate, N (1), N (12)-diacetylspermine. The PAO inhibitor, MDL-72,527, only partially blocked oxidation of spermine while a previously reported PAO substrate, N (1)-( n -octanesulphonyl)spermine, potently inhibited the reaction. Overall, the data indicate that the enzyme represents a novel mammalian oxidase which, on the basis of substrate specificity, we have designated spermine oxidase in order to distinguish it from the PAO involved in polyamine back-conversion. The identification of an enzyme capable of directly oxidizing spermine to spermidine has important implications for understanding polyamine homoeostasis and for interpreting metabolic and cellular responses to clinically relevant polyamine analogues and inhibitors. << Less

  Biochem. J. 367:665-675(2002) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.