Increase In ODC Activity Research Articles

Changes in ornithine decarboxylase during early implantation in the rat.

Ornithine decarboxylase activity was compared in the right and left horns of unilaterally ovariectomized rats on Days 4 and 5 of pregnancy. It was found that enzyme activity in the pregnant horn was significantly increased over that of the contralateral empty horn by 0400 h on Day 5 before implantation of the blastocyst occurred and reached maximum levels by 0900 h. Similar changes were not observed in the intact horns of uteri from unilaterally ovariectomized rats mated with vasectomized males even though eggs were present. However, intraluminal injection of arachis oil at 1000 h on Day 5 into those horns, a treatment producing massive deciduomas, led to large increases in ODC activity in the treated horn within 5 h. Similar increases were not induced by laparotomy. The data indicates that the decidual response induced by the blastocyst has already commenced by 0400 h on Day 5, in agreement with previous conclusions based on studies of RNA synthesis.

The regulation of ornithine decarboxylase in Neurospora crassa

The regulation of ornithine decarboxylase (ODC; l -ornithine carboxylase, EC 4.1.1.17) in Neurospora crassa was investigated. Putrescine, spermidine, and spermine inhibited the enzyme in vitro and caused in vivo repression. Of the three polyamines, putrescine was the strongest inhibitor. Mg 2+ reversed the in vitro inhibition of ODC by putrescine. Growth of cultures of wildtype 74A and the arginaseless mutant aga on arginine-supplemented medium caused 4- and 100 fold increases in ODC activity, respectively. Treatment of cultures with cycloheximide abolished the arginine-mediated increase in ODC activity. Differences in total enzymatic activity, coenzyme requirement, and temperature stability of ODC grown on minimal and arginine-supplemented media suggest that Neurospora possesses two forms of the enzyme.

Nerve growth factor-mediated selective induction of ornithine decarboxylase in rat pheochromocytoma; a cyclic amp-independent process

Nerve growth factor (NGF) is a protein indispensible for the normal development, survival and maintenance of function of peripheral sympathetic neurons throughout life, and of spinal sensory neurons during a brief period of their development [ 1,2] . Beyond the general promotion of growth and the stimulation of fiber outgrowth from sympathetic neurons [l] , the selective induction of tyrosine hydroxylase (TH) and dopamine fi-hydroxylase (DBH) is one of the most characteristic biochemical effects of NGF on adrenergic neurons and adrenal chromaffm cells [3,4] . Recently, a clonal cell line (PC1 2) was established from a transplantable rat adrenal pheochromocytoma [ 51. This cell line shows a high degree of differentiation, involving synthesis, storage, release and uptake of the adrenergic transmitter [5,6], reflecting functional properties of adrenergic neurons. Moreover, as a further characteristic property of adrenergic neurons, PC 12 cells respond with fiber outgrowth to NGF [S] , although they lack a selective induction of TH, another characteristic response to NGF [7] . So far, neuronal fiber outgrowth is the only common response of all target cells to NGF, whereas a corresponding common biochemical response has not yet been described. Since PC12 cells respond to NGF with fiber outgrowth but not with selective TH induction, they seemed to be suitable for study of the biochemical responses to physiological levels of NGF which are common to all target cells of NGF. We report that NGF produces a specific increase in the activity of ornithine decarboxylase (EC 4.1 .l .17, L-ornithine carboxy-lyase) (ODC), the rate-limiting enzyme in polyamine biosynthesis [8] , This increase of ODC can be abolished by cycloheximide indicating that the rise ln ODC activity is protein synthesisdependent. In addition, we report that NGF-mediated increase in ODC activity is a cyclic AMP independent process.

Ovine placental lactogen stimulation of ornithine decarboxylase activity in brain and liver of neonatal rats

Ovine placental lactogen (oPL), growth hormone (oGH), prolactin (oPRL) and human placental lactogen (hPL) were administered intracisternally (ic) or intraperitoneally (ip) to 17 day old rats and brain and liver ODC activities determined four hours later. When given ic, oPL, oGH and oPRL caused significant increases in brain ODC activity, while hPL had no significant effect. After ip administration, oPL and oGH also caused a significant increase in brain as well as liver ODC activity but oPRL and hPL were without significant effect. The stimulation of polyamine metabolism by oPL together with earlier reports of its potent somatotropic effects and its high concentration in the fetus supports the hypothesis that oPL may be important in the regulation of fetal growth.

Effect of α-methyl ornithine on ornithine decarboxylase activity of rat hepatoma cells in culture

DL-α-methyl ornithine (α-MeOrn), a potent competitive inhibitor of ornithine decarboxylase (L-ornithine carboxy-lyase EC 4.1.1.7) (ODC), caused an increase of ODC activity of rat hepatoma tissue culture cells cultured in the presence of the compound. The effect was seen only when there was newly synthesized ODC present. The α-MeOrn mediated increase of ODC activity was independent of RNA synthesis and was expressed at a post-transcriptional level. ODC half-life, measured after cycloheximide treatment, was increased by a factor of three in the presence of α-MeOrn, suggesting the compound slowed enzyme degradation perhaps by its ability to enter the active site.

Mechanism of allopurinol-mediated inhibition and stabilization of human orotate phosphoribosyltransferase and orotidine phosphate decarboxylase

Allopurinol ribonucleotide and oxipurinol-7-ribonucleotide appeared to be strong inhibitors of orotidine phosphate decarboxylase in human hemolysates. The enzyme exhibited bimodal kinetics. The ribonucleotides of allopurinol and oxipurinol caused an inhibition of orotate phosphoribosyltransferase, which appeared to be due to accumulation of OMP. Inhibition by OMP was competitive with respect to phosphoribosylpyrophosphate with a K i value of 11 μM. The inhibition of ODC and OPRT activity may cause the increased urinary excretion of orotidine and orotic acid, respectively, observed after allopurinol therapy. Values measured for OPRT activity in intact erythrocytes and in hemolysates agreed very well. Therefore OPRT activity does not decrease during cell lysis and extraction. Hypoxanthine-guanine phosphoribosyltransferase deficiency as well as allopurinol therapy led to a marked increase in OPRT and ODC activities in human hemolysates. In lysates from leukocytes only a slight increase of ODC activity was observed, while OPRT activity did not differ significantly from the controls. In vitro incubations of hemolysates demonstrated a considerable increase of the stability of OPRT by addition of OMP or PRPP and of ODC by addition of OMP, PRPP, UMP and the ribonucleotides of allopurinol and oxipurinol. These findings suggest that the apparent increase of OPRT and ODC activity after allopurinol therapy is due to stabilization of the enzymes during the life span of the erythrocytes.

The inhibition of the induction of ornithine decarboxylase by cations

L1210 cells reinitiate growth after dilution with fresh medium; during this time there occurs a transient increase in ornithine decarboxylase (EC4.1.1.17) (ODC) activity. The addition of 10 to 20 mM Na +, K + or Mg ++ completely inhibits this induction of ODC activity with no effect on cell growth. These cations also inhibit the increase of ODC activity in neuroblastoma cells and in H-35 cells which is induced by prostaglandin E 1 plus 3-isobutyl-1-methyl-xanthine and by 15% fetal calf serum respectively. This inhibitory effect of low levels of cations on the induction of ODC activity in different cell lines suggests that the intracellular function of ODC, and of the products of the reaction it catalyzes (putrescine, spermidine and spermine), may be intimately involved with changes in cation pools.

Effect of growth conditions on the activity of ornithine decarboxylase in cultured hepatoma cells. II. Effect of serum and insulin.

AbstractHTC cells incubated in the absence of serum for more than 14 hours have very low levels of ornithine decarboxylase, the first enzyme on the pathway of polyamine synthesis. Readdition of serum causes an increase in the activity of ODC, reaching a maximum on average 17 times above the basal level after five hours. This increase is due in part to a decrease in the apparent rate of degradation of ODC, and also to a stimulation of its synthesis. Within the first two hours the serum induction of ODC is resistant to Actinomycin D. Insulin at 5 μm/ml alsocauses an increase in ODC activity but only after a delay of two hours, in contrast to its more rapid stimulation of tyrosine transaminase activity.