Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:4.1.1.17 (ornithine decarboxylase)
6,351 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effects of DL-alpha-difluoromethylornithine (RMI 71782; DFMO) on the tumours induced in female rats by a single oral administration of 20 mg 7,12-dimethyl-benz[a]anthracene (DMBA) have been investigated. 2. Treatment with DFMO (2% aqueous solution as sole drinking fluid) starting 30 days after administration of DMBA resulted in markedly fewer animals with tumours and greater than 90% reduction in the total number of tumours. 3. In rats bearing at least one palpable tumour, treatment with DFMO (2% in the drinking water) slowed significantly the rate of appearance of new tumours but affected to only a minimal extent the growth of existing tumours. Tumour ornithine decarboxylase activities and putrescine concentrations were reduced by treatment with DFMO; the activity of S-adenosyl-L-methionine decarboxylase was increased and the concentration of spermine either remained unchanged or increased depending on the length of treatment. 4. Cyclophosphamide, 100 mg/kg, injected once then repeated after 10 days, altered neither the rate of appearance of new tumours nor the growth of the existing tumours. Combined treatment with DFMO plus cyclophosphamide resulted in regression of the majority of tumours existing at the start of treatment and a marked reduction in the rate of appearance of new tumours. 5. In conclusion, DFMO has clear antitumoral activity against the rat mammary tumour induced by DMBA. The effects are manifested principally as a decreased rate of tumour appearance but meaningful effects on tumour growth are observed if the drug is administered during early tumour development or in combination with cyclophosphamide.
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PMID:Effects of DL-alpha-difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase, on the rat mammary tumour induced by 7,12-dimethylbenz[a]anthracene. 681 56

Lymphocyte mitogenesis is generally assessed by measuring the incorporation of [(3)H]thymidine into DNA. By this criterion, small lymphocytes, which are activated by relatively low doses of concanavalin A, are either unresponsive to or inhibited by higher concentrations. Because lymphocytes begin to synthesize DNA about 24 hr after addition of mitogen, the response is far removed temporally from the initial stimulus. We have chosen to use the induction of S-adenosylmethionine decarboxylase (S-adenosyl-L-methionine carboxy-lyase, EC 4.1.1.50) to assess early activation events in bovine lymphocytes. Adenosylmethionine decarboxylase induction is bimodal, with an initial phase beginning 3 hr after addition of concanavalin A and a second wave coinciding with the onset of DNA synthesis. The initial accumulation of the decarboxylase (0-9 hr) in cultures treated with "nonmitogenic" levels of concanavalin A (108 mug/ml) was similar to that observed in cultures stimulated with optimally mitogenic doses (18 mug/ml). The early induction of ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) was also similar under these two culture conditions. However, the second phase of adenosylmethionine decarboxylase accumulation, the induction of thymidine kinase (ATP: thymidine 5'-phosphotransferase, EC 2.7.1.21), and DNA replication were blocked at the higher concentrations of concanavalin A. The inhibition of late events by high doses of concanavalin A was reversible. Cells treated with alpha-methyl-D-mannopyranoside 25 hr after addition of a high dose of lectin responded with a second period of adenosylmethionine decarboxylase accumulation, induction of thymidine kinase, and progression through S phase. These results suggest that initial lymphocyte activation occurs normally at high doses of concanavalin A, but that the cells are reversibly blocked prior to induction of "late" enzymes and progression through S phase.
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PMID:Activation of early enzyme production in small lymphocytes in response to high, nonmitogenic concentrations of concanavalin A. 693 33

The biphasic increase of ornithine decarboxylase activity in mouse mammary gland in organ culture occurs with a hormone-independent first peak and a hormone-dependent second peak. The data presented indicate that a change in the osmolarity of the cellular environment is the major contributing factor for the emergence of the hormone-independent ornithine decarboxylase activity in mammary explants. Thus, incubation of mammary explants for 3 h in a medium diluted 53% with distilled water results in approx. 1000-fold stimulation of enzyme activity over the initial level, whereas a similar dilution of the medium with 0.18 M NaCl or 0.3 M sucrose blocks the increase. The increase in enzyme activity is similarly affected by a reduction of the concentration of NaCl in the culture medium. The hypoosmotic stimulation of ornithine decarboxylase activity appears to be affected at a posttranscriptional level, and is enhanced further by the actions of insulin and prolactin. The hypoosmotic enhancement of ornithine decarboxylase activity produces a large increase in the intracellular concentration of putrescine in mammary explants. However, neither the concentration of spermidine and spermine nor the activity of S-adenosyl-L-methionine decarboxylase is affected. In addition, studies of putrescine transport in mammary explants show that hypotonicity causes an increase in the rate of influx and a decrease in efflux of putrescine with enhancement of intracellular putrescine accumulation. On the other hand, the uptake of spermidine, spermine, amino acids, sugar, and a lipophilic cation, triphenylmethylphosphonium is unaffected. These data suggest a possibility that osmotic alteration in cellular environment causes an incresed need for putrescine in mammary cells, resulting in stimulation of ornithine decarboxylase activity, which may represent a cellular mechanism for maintaining the homeostasis of the intracellular cationic environment.
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PMID:Regulation of ornithine decarboxylase in cultured mouse mammary gland by the osmolarity in the cellular environment. 698 7

The activity of S-adenosyl-L-methionine decarboxylase (S-adenosyl-L-methionine carboxy-lyase, EC 4.1.1.50) purified from mouse mammary gland can be stimulated by physiological concentrations of putrescine (Ka = 5 x 10(-7) M). In contrast, the elevation of the intracellular concentrations of putrescine in cultured mouse mammary tissue by exogenous addition of putrescine or by cultivation of the tissue in hypotonic medium results in the decrease in both the activity and the amount of the enzyme in tissue. Conversely, the addition of 1 mM alpha-methyl ornithine, an inhibitor of ornithine decarboxylase, causes augmentation of the activity and the amount of S-adenosyl-L-methionine decarboxylase, despite its inhibitory action on insulin-stimulated increase in the concentration of putrescine. These data suggest that putrescine can act as a 'negative' regulator of the enzyme in this system.
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PMID:Putrescine and the regulation of S-adenosyl-L-methionine decarboxylase in cultured mouse mammary gland. 699 34

The activity levels of L-ornithine carboxy-lyase (ODC) (E.C. 4.1.1.17) and S-adenosyl-L-methionine carboxy-lyase (SAM-D) (E.C.4.1.1.50) were determined in individual papillomas induced in mouse skin by a two-stage technique, and in normal mouse epidermis. Cycloheximide treatment abolished both enzyme activities. In normal epidermis the ODC activity was barely detectable, whereas the tumors exhibited high levels of ODC. Levels of SAM-D activity above those of normal epidermis were detected in some papillomas, but in contrast to ODC the SAM-D activity levels were not consistently increased in skin tumors. By pooling a great number of papillomas, the variations in ODC and SAM-D activities between different papillomas could be minimized so that reliable measurements of the biological half-lives of ODC and SAM-D in the tumors were obtained using cycloheximide treatment. The half-life of SAM-D in squamous papillomas was 45 min, almost identical to the 41 min half-life of the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced level of this enzyme in normal mouse epidermis. In contrast, the ODC activity of the mouse skin papillomas declined at a rate similar to that in TPA-treated epidermis for only the first 15-20 min after cycloheximide injection. Thereafter, at time points when protein synthesis was approximately 90% inhibited, the ODC activity reverted to high levels. These results show that the high level of ODC activity in squamous papillomas is stabilized. This observation is compatible with the hypothesis that the control mechanism of the ODC activity level in these tumors is severely deranged. This change in polyamine turnover pattern may be related to altered differentiation of the epidermal cells, which constitute the main bulk of cells in these tumors.
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PMID:Ornithine decarboxylase activity in chemically induced mouse skin papillomas. 708 70

A single topical application of 17 nmol 12-O-tetradecanoyl-phorbol-13-acetate (TPA) to the skin of hairless mice induces characteristic transient alterations in the epidermal cells turnover and maturation (0.96 h), associated in time with characteristic changes in the activities of L-ornithine carboxy-lyase (E.C. 4.1.1.17) (ODC) and S-adenosyl-L-methionine carboxy-lyase (E.C.4.1.1.50) (SAM-D) and in the accumulation of polyamines. The effects on these responses of local pretreatment of the skin with retinoic acid 1 h prior to TPA were investigated at selected time points. Retinoic acid inhibited the TPA-induced ODC activity and the ensuing accumulation of putrescine, but did not alter the TPA-induced SAM-D activity or the molar ratio of spermidine/spermine. This pretreatment also decreased in number of dividing basal cells in the first TPA-induced synchronized wave of proliferating cells. However, during the subsequent period of proliferation, the number of dividing cells in the retinoic acid pretreated group was comparatively increased. Hence, at four levels of retinoic acid (0.17, 1.70, 17.0 and 170 nmol), which all inhibited the TPA-induced ODC effectively, there was no change in the total number of basal cells that divided during 16-48 h after TPA-application. Theory is put forward the retinoic acid might exert its antitumorigenic effect during tumor promotion with TPA by interfering with the rate and/or quality of epidermal cell maturation, rather than by inhibiting cell proliferation.
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PMID:Effect of retinoic acid pretreatment on 12-O-tetradecanoylphorbol-13-acetate-induced cell population kinetics and polyamine biosynthesis in hairless mouse epidermis. 708 72

The concentrations of putrescine, spermidine and spermine and the activities of ornithine decarboxylase (ODC) and S-adenosyl-L-methionine decarboxylase (SAM-D) were investigated in fast muscle subjected to chronic low-frequency electrical stimulation. Both ODC and SAM-D activities increased markedly between 18 and 48 h of stimulation. Changes in enzyme activities were followed by phasic elevations in the concentrations of putrescine, spermidine and spermine. Peak levels were reached first by putrescine at 3-4 days, followed by spermidine at about 9 days and then by spermine at about 11 days. A possible relationship was sought between these events and changes produced in vitro in the phosphorylation pattern of cytoplasmic proteins and the total activity of cyclic AMP-dependent protein kinase. However, during the early stages of stimulation, no prominent changes were seen either in the phosphorylation pattern or in the activity of cyclic AMP-dependent protein kinase. These characteristics changed significantly at a later stage (by 12 days of stimulation) and became indistinguishable from those of slow muscle by 3 to 4 weeks of stimulation.
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PMID:Early events in the response of fast skeletal muscle to chronic low-frequency stimulation. Polyamine biosynthesis and protein phosphorylation. 715 Feb 42

The natural polyamines spermine and spermidine, and the diamine putrescine, were extracted from rooster testis cells separated by sedimentation at unit gravity, and from vas-deferens spermatozoa. The ratios spermine/DNA and spermidine/DNA were kept relatively constant throughout spermatogenesis, whereas the ratio putrescine/DNA rose in elongated spermatids. The cellular content of spermine, spermidine and putrescine decreased markedly in mature spermatozoa. Two rate-limiting enzymes in the biosynthetic pathway of polyamines, ornithine decarboxylase and S-adenosyl-L-methionine decarboxylase, showed their highest activities at the end of spermiogenesis and were not detectable in vas-deferens spermatozoa. A marked reduction in cell volume during spermiogenesis without a parallel decrease in the cellular content of polyamines suggests the possibility that the marked changes in chromatin composition and structure occurring in rooster late spermatids could take place in an ambience of high polyamine concentration.
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PMID:Cellular content and biosynthesis of polyamines during rooster spermatogenesis. 715 1

In vitro, 5-fluoropentane-1,4-diamine and 5,5-difluoropentane-1,4-diamine are potent enzyme-activated inhibitors of rat liver ornithine decarboxylase (EC 4.1.1.17). The two alpha-fluoromethyl derivatives of putrescine activate to different degrees S-adenosyl-L-methionine decarboxylase (EC 4.1.1.50). The difluoromethyl derivative differs from the monofluoromethyl derivative in that it is not a substrate of diamine oxidase (EC 1.4.3.6), but is a better substrate of mitochondrial monoamine oxidase (EC 1.4.3.4) than the monofluoromethyl derivative. In vivo, a single i.p. injection of 200 mg/kg of 5-fluoropentane-1,4-diamine to rats causes a marked decrease of the ornithine decarboxylase activity in the ventral prostate and to a lesser extent in the thymus, whereas 5,5-difluoropentane-1,4-diamine causes only a slight decrease of this enzyme activity in the prostate and does not affect it in the thymus. Both compounds produce a decrease of 4-aminobutyrate: 2-oxoglutarate aminotransferase (EC 2.6.1.19) activity in the brain. The differences observed between the biochemical properties of the two alpha-fluoromethyl derivatives of putrescine are discussed in relation to the pKa value of the alpha-amino group which decreases from 7.75 for 5-fluoropentane-1,4-diamine to 6.4 for 5,5-difluoropentane-1,4-diamine.
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PMID:alpha-Monofluoromethyl and alpha-difluoromethyl putrescine as ornithine decarboxylase inhibitors: in vitro and in vivo biochemical properties. 715 64

Mouse brain ornithine decarboxylase (ODC) activity is high at the time of birth, whereas S-adenosyl-L-methionine decarboxylase (SAM-DC) activity is low. ODC activity, and putrescine, spermidine and spermine concentrations decline rapidly during postnatal development to the low level characteristic of mature brains, while SAM-DC activity behaves in the opposite manner. The fluctuations in mouse brain polyamine metabolism are in accord with those found in the rat. The apparent Km values of ODC and SAM-DC for their substrates decline parallel with the decrease of substrate and product concentrations during ontogeny suggesting substrate and/or product dependent regulation of polyamine synthesis in the developing brain.
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PMID:Developmental changes in mouse brain polyamine metabolism. 717 63


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