title: Transgenic mice overexpressing ornithine and S-adenosylmethionine decarboxylases maintain a physiological polyamine homoeostasis in their tissues.
abstract: Recent work has shown that transgenic mice overexpressing human ornithine decarboxylase display no marked changes in the tissue concentrations of spermidine or spermine in spite of a dramatic increase in putrescine levels. In the tissues of transgenic mice carrying the human spermidine synthase gene and in those of hybrid mice overexpressing both ornithine decarboxylase and spermidine synthase, spermidine and spermine levels remain within normal limits. To test whether the amount of the propylamine group donor, decarboxylated S-adenosylmethionine, limits the conversion of putrescine into the higher polyamines, we have produced transgenic mouse lines harbouring the rat S-adenosylmethionine decarboxylase gene in their genome. However, neither these mice nor the hybrid mice overexpressing both ornithine decarboxylase and S-adenosylmethionine decarboxylase displayed significant changes in their spermidine and spermine tissue levels. To study the mechanism by which cells maintain the constancy of the polyamine concentrations, we have determined the metabolic flux of polyamines in transgenic primary fibroblasts using pulse labelling. The results indicate that the polyamine flow is faster in transgenic primary fibroblasts than in non-transgenic fibroblasts and that the intracellular homoeostasis of higher polyamines is maintained at least partly by the acetylation of spermidine and spermine and their secretion into the medium.
authors.affiliation: Biocenter and Department of Biochemistry, University of Oulu, P.O. Box 400, FIN-90571 Oulu, Finland,
authors.forename: R
authors.initials: R
authors.lastname: Heljasvaara
authors.forename: I
authors.initials: I
authors.lastname: Veress
authors.forename: M
authors.initials: M
authors.lastname: Halmekytö
authors.forename: L
authors.initials: L
authors.lastname: Alhonen
authors.forename: J
authors.initials: J
authors.lastname: Jänne
authors.forename: P
authors.initials: P
authors.lastname: Laajala
authors.forename: A
authors.initials: A
authors.lastname: Pajunen
mesh_terms: D012437:Adenosylmethionine Decarboxylase / Q000378:metabolism*; D000818:Animals; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008099:Liver / Q000201:enzymology; D051379:Mice; D008822:Mice, Transgenic; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D011073:Polyamines / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D051381:Rats
chemical_list: D011073:Polyamines; D012313:RNA; D009955:Ornithine Decarboxylase; D012437:Adenosylmethionine Decarboxylase