Detection of Ornithine Decarboxylase Antizyme in Mouse Brain

Abstract

Ornithine decarboxylase, the rate-limiting enzyme in polyamine synthesis, is known to be regulated by a macromolecular inhibitor, termed antizyme, in a number of cellular systems. The present results show that the antizyme is also a functional component of polyamine metabolism in the brain. It could be demonstrated both in normal randomly selected mice and in animals which had been subjected either to intracerebroventricular injection of saline, which is known to cause a transient activation of ornithine decarboxylase, or to 1,3-diamino-2-propanol, an antizyme-inducing agent. When compared to tissues or cell systems studied so far, the cytosol fraction from mouse brain homogenate appeared to contain an exceptionally high amount of antizyme, that was bound to some material other than active ornithine decarboxylase. This feature was seen in all the animal groups studied, being most prominent after saline injection, when the amount of dissociable antizyme exceeded 14-fold the corresponding released ornithine decarboxylase activity. In untreated animals the excess was about eightfold and after 1,3-diamino-2-propanol about fivefold.

The existence of ornithine decarboxylase‐antizyme complex in germinated barley seeds

“…Occurrenee of ODC-Az eomplex as a normal eomponent was deseribed for rat liver and Hj, cells (Heller et al, 1977), and eonfirmed for mouse brain (Hietala 1983) and hepatoma eells (MeCann et al 1977). In RK,, kidney cells the ODC-Az complex exists in a partieulate fraction (Murakatni et al 1986).…”

Activation of rat brain ornithine decarboxylase by GTP

“…It is unlikely that GTP is a limiting factor in vivo, and thus the brain ODC may always be in an active state, when/if it is dissociated from the ODC-antizyme complex. It has been reported that, in the mouse brain, a large amount of ODC is bound to the antizyme as an inactive complex, representing the storage form of the enzyme, which can be rapidly activated by dissociation for local needs [7,9]. To our knowledge there is no information about the histological localization of ODC or antizyme in brain.…”

“…Ornithine decarboxylase (ODC; EC 4.1.1.17) is a rate-limiting enzyme in the biosynthesis of polyamines in mammalian cells [1][2][3][4]. Its activity in the adult mouse brain is very low compared with that in other tissues [5][6][7][8]. However, brain contains a high amount of immunoreactive enzyme protein [9].…”

“…However, brain contains a high amount of immunoreactive enzyme protein [9]. This apparent contradiction can be explained by the fact that the brain cytosol fraction is rich in ODC-antizyme complex [7], which also displays antigenicity [9,10]. The antizyme inhibits the enzyme by noncovalent binding [11] and mediates polyamine-induced acceleration of ODC degradation [12][13][14][15][16][17].…”

“…The antizyme inhibits the enzyme by noncovalent binding [11] and mediates polyamine-induced acceleration of ODC degradation [12][13][14][15][16][17]. The ODC-antizyme complex can be dissociated by treatment with high salt concentrations, and at least part of the enzyme is released as catalytically active [7,[18][19][20][21][22].…”