Changes in ornithine decarboxylase and antizyme activities in developing mouse brain

Abstract

A macromolecular inhibitor to ornithine decarboxylase (ODC) present in mouse brain was identified as ODC antizyme [Fong, Heller & Canellakis (1976) Biochim. Biophys. Acta 428, 456-465; Heller, Fong & Canellakis (1976) Proc. Natl. Acad. Sci. U.S.A. 73, 1858-1862] on the basis of kinetic properties, Mr and reversal of its inhibition by antizyme inhibitor. The brain antizyme, however, did not cross-react immunochemically with any of seven monoclonal antibodies to rat liver antizyme. ODC activity in mouse brain rapidly decreased after birth, in parallel with putrescine content, and almost disappeared by 3 weeks of age. Free antizyme activity appeared shortly after birth and increased gradually, whereas ODC-antizyme complex already existed at birth and then gradually decreased. Thus total amount of antizyme remained about the same throughout the developmental period in mouse brain. In addition to ODC-antizyme complex, inactive ODC protein was detected by radioimmunoassay in about the same level as the complex at 3 weeks of age. Upon cycloheximide treatment, both free ODC activity and ODC-antizyme complex rapidly disappeared, although free antizyme and the inactive ODC protein were both quite stable.

Expression of the Genes Coding for Ornithine Decarboxylase and Its Regulatory Protein Antizyme in the Developing Rat Brain

“…In the whole mouse brain, ODC catalytic activity is highest at birth and declines rapidly to a low adult level by postnatal day 21, while free AZ activity increases after birth [24], These results indicate that AZ may play an important role in the regulation of ODC activity and polyamine levels in the developing brain. Expression of ODC mRNA in developing mouse whole brain [25] and in rat cortex and cerebellum [20] has been described but there has been no study of the region-specific ontogenic pattern of ODC and particularly its relationship to antizyme gene expression.…”

“…An inverse relationship between ODC and antizyme activity during development has been reported in the brain [24]. Antizyme activity is low at birth but increases about 7-fold by 4 weeks.…”

Expression of a Novel Human Ornithine Decarboxylase-like Protein in the Central Nervous System and Testes

“…The authors proposed that the physiological ODC activity in these organs is repressed by distal silencer elements that were not included in the transgene construct. The expression of AZ also varies in different parts of the adult brain largely paralleling the expression of ODC (9,13). A third variant of AZ, antizyme 3 (AZ3), was recently cloned and found to be exclusively expressed in the testes (14).…”

Expression of ODC and its regulatory protein antizyme in the adult rat brain

“…After cerebral ischemia ODC is up-regulated also in regions where no cellular damage usually occurs (Keinänen et al, 1997). In mammalian brain, ODC activity is highest at birth and thereafter declines during the first weeks or months to a low adult level (Laitinen et al, 1982;Onoue et al, 1988;Morrison et al, 1998), although the amount of immunoreactive enzyme is still relatively high (Laitinen et al, 1985). In the adult brain a large amount of ODC is bound to the Az as an inactive complex and it has been suggested that the bound ODC represents the storage form of the enzyme that can be rapidly activated by dissociation for local needs (Laitinen et al, 1985(Laitinen et al, , 1986.…”