Increase In On Ornithine Decarboxylase Activity Research Articles

Hexachlorobenzene-induced early changes in ornithine decarboxylase and protein tyrosine kinase activities, polyamines and c-Myc, c-Fos and c-Jun proto-oncogenes in rat liver.

Hexachlorobenzene (HCB) is a lipophilic chemical compound that is widely distributed in the environment. HCB is known to cause liver tumors in experimental animals. In the present study the in vivo effect of HCB treatment on ornithine decarboxylase (ODC) and protein tyrosine kinase (PTK) activities, free polyamine content, and c-Myc, c-Fos, and c-Jun protein levels in rat liver were investigated. HCB (1000 mg/kg body weight) increased hepatic immunodetectable c-Myc, c-Fos, and c-Jun levels after 6 h, and ODC activity and spermine and putrescine content after 18 and 24 h, while maximum stimulation of PTK activity occurred at 12 h. PTK and ODC activities varied in a dose-dependent manner. The time-course of c-Myc, c-Fos, and c-Jun protein levels was different for each proto-oncogene. They were all elevated at the second day of treatment, while only c-Fos and c-Jun remained elevated after 10 days of HCB exposure. These data jointly suggest that the increase in ODC activity may be the consequence of proto-oncogene induction. The alterations in PTK activity suggest that the growth factor signal transduction pathway may be involved in the regulation of the proto-oncogene levels or/and ODC activity. The decrease in PTK activity after the first day, even in the presence of alpha-D-Difluoromethylornithine (DFMO), an inhibitor of ODC activity, suggests that it is not regulated by polyamines. These results may be relevant to the early molecular events involved in HCB tumor promoter activity in rat liver.

Acute inhibitory effect of excess iodide on ornithine decarboxylase in the thyroid of propylthiouracil-treated rats.

Polyamines such as putrescine, spermidine and spermine have been thought to play an important role in thyroid growth induced by goitrogens. Reduced biosynthesis of these polyamines might play a role in the antigoitrogenic effects of excess iodide. This study was designed to examine the effect of potassium iodide (KI) on ornithine decarboxylase (ODC), a rate-limiting enzyme in the biosynthesis of polyamines. Thyroidal ODC activity, protein content and mRNA were increased in rats made hypothyroid by 10 days of propylthiouracil treatment. The increase in ODC activity was suppressed after subcutaneous injection of KI (13mg/kg body weight); the apparent half-life of ODC activity after the treatment was estimated to be 19 min and the maximum suppression (90%) was seen 60 min after the treatment. On the other hand, administration of iodine-containing compounds including L-thyroxine, L-di-iodotyrosine,amiodarone, iopanoic acid and erythrosine showed no significant effect on ODC activity. The inhibitory effect of excess iodide was not reversed by pretreatment with dibutyryl cAMP and theophylline. The amount of immunoreactive ODC protein was reduced by iodide treatment (40%). However, the decrease was not as great as the decrease in ODC activity (90%). No significant change in thyroidal ODC mRNA content was seen 1 and 3 h following KI treatment. These results suggest that excess iodide reduces ODC activity in the rat thyroid gland by a post-transcriptional mechanism.

Subdiaphragmatic vagotomy abolishes increase in ornithine decarboxylase activity of rat duodenal mucosa after ischemia-reperfusion in superior mesenteric artery.

In order to evaluate the systemic and neural factors on ornithine decarboxylase (ODC) activity of rat intestinal mucosa, ODC activity in duodenal mucosa, where blood flow did not decrease by superior mesenteric artery (SMA) occlusion, was compared to that of jejunal and ileal mucosa, where blood flow decreased to 90% of the initial value after SMA occlusion. Rats were allowed to recover after SMA occlusion before harvesting intestinal mucosa for measuring ODC activity. ODC activity in the jejunum and the ileum increased markedly 6 h after ischemia-reperfusion (I/R) and more than 72 h were required for ODC activity to return to normal. ODC activity in the duodenum did not change until 24 h after I/R, but the activity increased 48 h after I/R, and this increase continued for 2 days. Subdiaphragmatic vagotomy completely abolished the increase in ODC activity in the duodenum, whereas the same procedure had no influence on ODC activity in the jejunum or the ileum. These results indicate that a neural signal from the central nervous system via the efferent vagal nerve following I/R was an important factor in the increase in ODC activity of duodenal mucosa, where blood flow was not influenced by SMA occlusion.

Superinduction of ornithine decarboxylase by halogenated ribofuranosylbenzimidazoles

1. 1. The effect of dichlororibofuranosylbenzimidazole (DiCl-RB), an inhibitor of hnRNA synthesis and casein kinase-2 activity, on ornithine decarboxylase (ODC) was investigated in a difluoromethylornithine (DFMO) resistant, ODC overproducing cell line. 2. 2. In cells growing in the absence of DFMO, DiCl-RB provoked a marked, but transient increase in ODC activity and immunoreactive ODC content. 3. 3. The ODC response to DiCl-RB was prevented by cycloheximide and was not due to stabilization of the enzyme. 4. 4. The dibromo derivative analogue (DiBr-RB) exerted similar effects on ODC, but was effective at lower concentrations. 5. 5. The halogenated ribofuranosylbenzimidazoles were ineffective in cells growing in the presence of DFMO and containing higher levels of ODC protein.

Induction of Ornithine Decarboxylase in Cerebral Cortex by Excitotoxin Lesion of Nucleus Basalis: Association with Postsynaptic Responsiveness and N‐Methyl‐d‐Aspartate Receptor Activation

The major cholinergic innervation of the rat cerebral cortex arises from the nucleus basalis in the basal forebrain. Introduction of the excitotoxins kainate or ibotenate into the nucleus basalis by stereotaxic injection results in degeneration of the cholinergic cells. We have investigated the effect of this excitotoxic action on ornithine decarboxylase (ODC) activity and cholinergic responsiveness in the cerebral cortex. A massive and rapid induction of ODC activity was seen in ipsilateral cortex after injection of excitotoxin. A maximal increase in ODC activity of 268 times the control value was seen in ipsilateral cerebral cortex 8 h after lesioning. Thereafter, ODC activity declined but remained significantly greater than control levels for 32 h. Pretreatment of animals with the irreversible ODC inhibitor difluoromethylornithine prevented the induction of ODC by kainate. Tissue content of the ODC product putrescine showed a marked increase in cerebral cortex ipsilateral to the lesion, increasing sevenfold at 24 h, the maximal concentration reached. After 24 h, the level of putrescine decreased but remained significantly elevated above control values for 5 days. Levels of the polyamines spermidine and spermine were unaffected by lesioning. Increases on ODC activity of much smaller magnitude were also seen in brain regions not directly innervated from the ipsilateral nucleus basalis. However, the response in ipsilateral cortex was found to be dependent on an intact projection from nucleus basalis to cortex. The induction of ODC was shown to be prevented by treatment of rats with MK-801, a result indicating the involvement of N-methyl-D-aspartate (NMDA) receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Histamine H 2-receptor mediated activation of neonatal rat brain ornithine decarboxylase in vivo

The effect of histamine (HA) administered via intracerebroventricular injection on ornithine decarboxylase (ODC) activity was studied in neonatal rat brain. The HA effect was dose and time dependent. Maximal increase in ODC activity was achieved 2 hr after administration of 10 μg HA (38% over control levels). Impromidine (HA H 2-agonist) mimicked the effect of HA on ODC and ranitidine (HA H 2-antagonist) inhibited the response to HA. Neither 2-thiazolylethylamine (HA H 1-agonist) nor mepyramine (HA H 1-antagonist) modified control ODC activity. The HA-releasers, compound 48/80 and polymixin B sulfate, elicited an increase in brain ODC activity of 35% and 32%, respectively, over the control value.

Ornithine decarboxylase activity during rat spermatogenesis in vivo and in vitro: selective effect of hormones and growth factors.

We have established the patterns of ornithine decarboxylase activity (an enzyme related to cell growth, differentiation, and proliferation) during rat testicular development and studied the effect of epidermal growth factor (EGF), platelet-derived growth factor (PDGF), transforming growth factor-type beta (TGF-beta), and a serum-free, hormone/growth factor-supplemented medium (TKM) on ornithine decarboxylase (ODC) activity in Sertoli-spermatogenic cell cocultures and cultured seminiferous peritubular cells prepared from sexually immature rats (20-22 days old). Results were correlated with timing of ODC activities during rat testicular development. We have found that: (1) although EGF, alone or combined with PDGF and TGF-beta, and TKM stimulated ODC activity in Sertoli-spermatogenic cell cocultures after 6 and 24 h of stimulation, PDGF exerted an inhibitory effect, and (2) cultured peritubular cells stimulated with EGF, PDGF, TGF-beta (and their combinations), and TKM displayed an increase in ODC activity after 6 h of stimulation, but ODC activities for most of these treatments declined considerably 24 h after stimulation. Light microscopic autoradiographic studies of [3H]thymidine labeled samples demonstrated that (1) clones of spermatogenic cells traverse S phase synchronously, (2) Sertoli cells are not significantly radiolabeled, probably because of contact inhibition achieved by high cell plating density, and (3) peritubular cells are significantly [3H]thymidine labeled in the presence of TKM, a culture medium that facilitates spermatogenic cell long-term viability and differentiation. We conclude that TKM and EGF have stimulatory effects on the biochemical pathway that precedes synchronous DNA synthesis in spermatogonia and preleptotene spermatocytes, and that ODC activity is a sensitive marker for monitoring these events.

Hyperthermia and polyamine biosynthesis: Decreased ornithine decarboxylase induction in skin and kidney after heat shock

The effect of hyperthermia treatments on ornithine decarboxylase (ODC) induction in mouse tissue was determined both ` in ` vitro and ` in ` vivo . ` In ` vitro , the addition of 12-O-tetradecanoylphorbol-13-acetate (TPA) to adult mouse skin pieces incubated at 37°C in serum-free MEM led to a dramatic increase in epidermal ODC activity 5 hours following treatment. In contrast, incubation temperatures of 40°C for the entire 5 hour incubation period rendered the skin pieces unresponsive to TPA for ODC induction. This inhibition of ODC induction was not the result of thermal skin kill, inactivation of TPA, or a general effect on epidermal protein synthesis. The inhibition of ODC induction could be reversed by switching the incubation temperature back to 37°C. ` In ` vivo , raising the core body temperature in male mice to 41°C for 1 hour resulted in a 78% decrease in kidney ODC activity. The kidney DNA synthesis and protein synthesis remained unaltered following the whole body hyperthermia treatments.

Relationships among uterine growth, ornithine decarboxylase activity and polyamine levels: studies with estradiol and antiestrogens

We have examined the effects of estradiol (E 2) and antiestrogen (AE) on ornithine decarboxylase (ODC) activity and uterine polyamine concentrations as an aid to understanding the dissimilar effects of E 2 and AE on uterine growth. ODC activity rises rapidly from very low levels in immature (day 20–23) rat uteri, showing two markedly (~ 500-fold) increased peaks of activity at 5 h and 16 h after E 2 (2 μg) injection. After AE (50 μg CI628 or U23469) treatment, the temporal increase in ODC activity is slow and only one major peak is found at 24 h. Daily injections of E 2 over a 3-day period evoke continued stimulation of uterine ODC activity; however, the same daily treatment regimen with AE results in stimulation of ODC activity only during the first day. After pretreatment with AE, E 2 can still elicit the early (5 h) peak of ODC activity, but the later (16 h) peak of ODC activity is blocked. Quantitation of uterine polyamines by high performance liquid chromatography reveals a 1.5–2-fold increase in the concentration of spermidine after 1 day of E 2 or AE exposure, with little change in putrescine or spermine levels. After 3 days of E 2, AE, or E 2 plus AE treatment, spermidine concentrations are elevated 2–2.5-fold and spermine concentrations are elevated 1.5-fold. Putrescine concentrations are unchanged. Hence, regardless of the different degree to which the uterus is stimulated to grow in response to E 2 and/or AE, there are corresponding changes in uterine ODC activity, such that polyamine concentrations are elevated to a similar extent in the E 2- or AE-treated uterus.

Amine synthesis in regenerating rat liver: effect of hypophysectomy and growth hormone on ornithine decarboxylase.

The effect of hypophysectomy and subsequent hormone therapy on ornithine decarboxylase (ORD) activity was examined in regenerating rat liver. Enzyme activity was determined by measuring the liberation of 14CO2 from carboxyl-labeled ornithine. In rats with intact pituitaries, ORD activity 4 hr after hepatectomy was 10 times that of sham-operated controls. Hypophysectomized rats failed to show an increase in ORD activity 4 hr after hepatectomy. A time course study showed that hypophysectomy resulted in a delayed increase and an early decline of ORD activity after partial hepatectomy. After the removal of thyroids, adrenals, ovaries, or testes, the increase in ORD activity 4 hr after hepatectomy was the same as in control animals. Treating hypophysectomized animals with triiodothyronine piior to hepatectomy produced a small but significant increase in enzyme activity. Growth hormone treatment produced a greater enhancement, although enzyme levels were still lower than those of control rats. Combined treatmen...