scholarly journals Effects of diamines on ornithine decarboxylase activity in control and virally transformed mouse fibroblasts

1979 ◽  
Vol 180 (1) ◽  
pp. 87-94 ◽  
Author(s):  
D R Bethell ◽  
A E Pegg

1. The induction of ornithine decarboxylase activity in mouse 3T3 fibroblasts or an SV-40 transformed 3T3 cell line by serum was prevented by addition of the naturally occurring polyamines putrescine (butane-1,4-diamine) and spermidine. Much higher concentrations of these amines were required to fully suppress ornithine decarboxylase activity in the transformed SV-3T3 cells than in the 3T3 fibroblasts. 2. Synthetic alpha omega-diamines with 3–12 carbon atoms also prevented the increase in ornithine decarboxylase activity induced by serum in these cells. The longer chain diamines were somewhat more potent than propane-1,3-diamine in this effect, but the synthetic diamines were less active than putrescine in the 3T3 cells. There was little difference between the responses of 3T3 and SV-3T3 cells to the synthetic diamines propane-1,3-diamine and heptane-1,7-diamine. 3. These results are discussed in relation to the control of polyamine synthesis in mammalian cells.

1981 ◽  
Vol 194 (3) ◽  
pp. 975-982 ◽  
Author(s):  
R Lanz ◽  
K Brune

The phorbol ester 12-O-tetradecanoylphorbol 13-acetate induces tumour promotion, inflammation, cell proliferation and prostaglandin release. Recent reports suggest that the prostaglandins released by 12-O-tetradecanoylphorbol 13-acetate (TPA) initiate a cascade of events leading to polyamine synthesis and cell proliferation. In experiments designed to test this contention, it was found that addition of TPA (1 microM to 1 nM) to confluent mouse 3T3 fibroblasts successively caused the release of prostaglandins E2 and I2, induction of the enzyme ornithine decarboxylase (EC 4.1.1.17), stimulation of [3H]thymidine incorporation into DNA, and cell proliferation. Pretreatment of the cells with the anti-inflammatory steroid dexamethasone (1 microM) or the non-steroidal anti-inflammatory drug indomethacin (1 microM) inhibited TPA-induced prostaglandin release. However, dexamethasone enhanced the other effects of TPA, whereas indomethacin was ineffective. Addition of prostaglandin E2 to the cultures did not induce ornithine decarboxylase activity and cell proliferation. Pretreatment of the cells with 1,3-diaminopropane (1 mM) or alpha-methylornithine (5 mM), inhibitors of polyamine synthesis, decreased TPA-induced ornithine decarboxylase activity without affecting DNA synthesis. TPA stimulated [3H]thymidine incorporation into DNA, even when the ornithine decarboxylase activity was completely blocked. These data suggest that the proliferative effect of TPA on 3T3 cells is independent of prostaglandin release and polyamine synthesis.


1985 ◽  
Vol 127 (3) ◽  
pp. 843-848 ◽  
Author(s):  
Elisa Vicenzi ◽  
Marina Bianchi ◽  
Mario Salmona ◽  
Maria Benedetta Donati ◽  
Andreina Poggi ◽  
...  

1977 ◽  
Vol 162 (1) ◽  
pp. 87-97 ◽  
Author(s):  
E E K Takyi ◽  
D J M Fuller ◽  
L J Donaldson ◽  
G H Thomas

The relationship between polyamine synthesis, growth and secretion in vivo was examined in ventral prostates from: (a) intact rats aged 3-60 weeks; (b) animals castrated for 7 days before injection with 5 alpha-dihydrotestosterone (17 beta-hydroxy-5-alpha-androstan-3-one), testosterone and 5 alpha-androstane-3 beta, 17 beta-diol for up to 10 days; (c) rats injected with the 3 beta, 17 beta-diol immediately after castration. Ornithine decarboxylase activity and the concentrations of putrescine, spermidine and spermine were measured. DNA-synthetic activity was monitored by measuring [125I]iododoxyuridine incorporation. An enhanced spermidine/spermine molar ratio reflected increased activity of the prostate. The ratio was higher (greater than 2) in prostates from sexually immature animals, than in the intact adult (1.5), suggesting that the ratio was indicative of the proliferative activity of the tissue. However, in the androgen-stimulated castrated rat, enhanced spermidine/spermine ratios tended to correlate with hypertrophy and secretion. In both sets of experiments there was a linear relationship between protein and spermidine content. High spermidine/spermine molar ratios were the consequence of a relatively low rate of accumulation of spermine relative to spermidine and protein. The relationship between polyamine synthesis and DNA-synthetic activity was investigated in cultured prostate. A combination of insulin (3 mug/ml) and testosterone (0.1 muM caused a stimulatory response in the incorporation of [125I]iododeoxyuridine and in cell division, despite a depleted polyamine content and low ornithine decarboxylase activity in the cultured tissue.


Blood ◽  
1978 ◽  
Vol 51 (6) ◽  
pp. 1021-1029
Author(s):  
WH Evans ◽  
CK Grieshaber ◽  
WC Miller ◽  
SM Wilson ◽  
HA Hoffman

Enriched fractions of mature and immature neutrophil granulocytes, isolated from guinea pig bone marrow, were assayed for ornithine decarboxylase activity and polyamine content. The results show that immature granulocytes contain at least ten times more ornithine decarboxylase activity and two times more spermidine than mature granulocytes. The incorporation of 14C-ornithine into putrescine and spermidine of intact immature granulocytes was three to four times and ten times, respectively, that of mature granulocyte preparations. Six hours after an inflammatory stimulus, transient increases of 14-fold and 3-fold in the activities of ornithine decarboxylase and S-adenosyl- L-methionine decarboxylase, respectively, were observed in immature bone marrow granulocytes. At this time the incorporation of 14C- ornithine into putrescine and spermidine in bone marrow granulocytes from stimulated animals was 14 times that of cells from controls. A maximum increase in DNA synthesis in these cells during the inflammatory response occurred 6 hr after the maximum increase in the polyamine synthetic activity. Together these data suggest that polyamine synthesis in the granulocyte compartment of the bone marrow is associated chiefly with immature proliferating cells and that increased polyamine synthesis precedes increased granulocyte proliferation in the bone marrow following an inflammatory stimulus.


Blood ◽  
1978 ◽  
Vol 51 (6) ◽  
pp. 1021-1029 ◽  
Author(s):  
WH Evans ◽  
CK Grieshaber ◽  
WC Miller ◽  
SM Wilson ◽  
HA Hoffman

Abstract Enriched fractions of mature and immature neutrophil granulocytes, isolated from guinea pig bone marrow, were assayed for ornithine decarboxylase activity and polyamine content. The results show that immature granulocytes contain at least ten times more ornithine decarboxylase activity and two times more spermidine than mature granulocytes. The incorporation of 14C-ornithine into putrescine and spermidine of intact immature granulocytes was three to four times and ten times, respectively, that of mature granulocyte preparations. Six hours after an inflammatory stimulus, transient increases of 14-fold and 3-fold in the activities of ornithine decarboxylase and S-adenosyl- L-methionine decarboxylase, respectively, were observed in immature bone marrow granulocytes. At this time the incorporation of 14C- ornithine into putrescine and spermidine in bone marrow granulocytes from stimulated animals was 14 times that of cells from controls. A maximum increase in DNA synthesis in these cells during the inflammatory response occurred 6 hr after the maximum increase in the polyamine synthetic activity. Together these data suggest that polyamine synthesis in the granulocyte compartment of the bone marrow is associated chiefly with immature proliferating cells and that increased polyamine synthesis precedes increased granulocyte proliferation in the bone marrow following an inflammatory stimulus.


1983 ◽  
Vol 216 (3) ◽  
pp. 597-604 ◽  
Author(s):  
A A Neyfakh ◽  
K N Yarygin ◽  
S I Gorgolyuk

The activity of ornithine decarboxylase (ODC) (the key enzyme of polyamine synthesis) in different poikilothermic animals depends on the temperatures at which they were kept just before the enzyme assay. With an increase in temperature (within physiological limits) ODC activity rises 5-25-fold within several hours. With a decrease in temperature it falls at the same rate. This effect, studied on loach (Misgurnus fossilis) embryos in detail, was also shown for embryos, larvae and some adult tissues of many species. It is not, however, observed in homoiothermic animals (chick embryos and mammalian cells), nor in bacteria and plants. Changes in polyamine concentrations follow those in ODC activity, but more slowly and to a lesser extent. It is assumed that modulation of ODC activity changes as a result of its synthesis and degradation. We suggest that the temperature-dependence of ODC activity is a mechanism of adaptation which maintains the optimal cellular concentration of polyamines for each temperature.


1978 ◽  
Vol 170 (3) ◽  
pp. 651-660 ◽  
Author(s):  
A E Pegg ◽  
C Conover ◽  
A Wrona

Rat liver ornithine decarboxylase activity was decreased by administration of putrescine (1,4-diaminobutane) or other diamines, including 1,3-diaminopropane, 1,5-diaminopentane and 1,6-diaminohexane. This effect was seen in control rats and in rats in which hepatic ornithine decarboxylase activity had been increased by administration of growth hormone (somatotropin) or thioacetamide. Loss of activity was not dependent on the conversion of putrescine into polyamines and was short-lived. Within 6h after intraperitoneal administration of 0.8 mmol/kg body wt., ornithine decarboxylase activity had returned to normal values. This return correlated with the rapid loss of the diamines from the liver, and the decrease in activity could be slightly prolonged by treatment with aminoguanidine, a diamine oxidase inhibitor. A decrease in ornithine decarboxylase activity by these diamines was accompanied by the accumulation in the liver of a nondiffusible inhibitor that decreased the activity of a purified ornithine decarboxylase preparation. The possibility that administration of non-physiological diamines that are not converted into polyamines might be useful for the inhibition of polyamine synthesis is discussed.


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