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)

Functional development of the sympathetic nervous system was examined in inbred Dahl salt-sensitive (S/JR) and salt-resistant (R/JR) rats by assessing cardiac and adrenal medullary responses to insulin-induced hypoglycemia at 2, 4, 8, 12, and 16 days of age. Heart ornithine decarboxylase (ODC) activity and adrenal catecholamine content were measured in pups of the two strains 3 hours after administration of either saline or insulin. The centrally mediated increase in sympathetic outflow caused by insulin-induced hypoglycemia was attended by induction of heart ODC activity and depletion of adrenal epinephrine (EPI). No significant differences were found overall between R/JR and S/JR strains with regard to either heart ODC activity or adrenal epinephrine. This was true for basal values obtained from saline-injected pups as well as for measures from insulin-injected pups. Functional innervation of the heart was present in pups of both strains as early as 2 days of age, while in the adrenal medulla a significant response to stimulation was not detected until 8 days of age. While the susceptibility for hypertension in the salt-sensitive animals may well be linked to increased sympathetic tone, the present findings indicate that S/JR rats do not have an accelerated development or a hyperresponsiveness of sympathetic input to either the heart or the adrenal medulla during the pre-weanling period.
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PMID:Sympathetic responses of the heart and adrenal medulla in developing Dahl hypertensive rats. 360 26

Relatively short-term treatment (8 weeks) of rats with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in the drinking water (100 mg/l) was shown to adequately initiate gastric carcinogenesis when 10% NaCl was simultaneously administered in the diet. Utilizing this MNNG plus high salt diet as the initiation stage of a two-step protocol, it was also established that subsequent dietary administration of NaCl (10% of the diet) for 32 weeks tended to enhance tumor development in the glandular stomach. Similar tumor promoting activity was demonstrated for other mucosal damaging agents, such as potassium metabisulfite and formaldehyde. Biological changes of the gastric mucosa were examined after chronic administration or a single oral intubation of NaCl. Morphological lesions observed included diffuse mild erosions, atrophy of the glands, and hyperplasia of the foveolar epithelium when given 10% NaCl diet chronically. After a single oral intubation of NaCl, increased tritiated thymidine labeling index and ornithine decarboxylase (ODC) activity were observed in both pyloric and fundic mucosa. No remarkable effects of NaCl were observed on the forestomach or duodenal mucosa. These results suggest that NaCl exerts an enhancing effect at both initiation and promotion steps within the two stage model system of the gastric carcinogenesis, and that these effects of NaCl are possibly related to its mucosal damaging activity.
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PMID:Enhancing effects of dietary salt on both initiation and promotion stages of rat gastric carcinogenesis. 391 94

Ornithine decarboxylase isolated from HTC cells was separated into two distinct charged states by salt-gradient elution from DEAE-Sepharose columns. This charge difference between the enzyme forms was maintained in partially purified preparations, but enzyme form II was observed to change to form I in a time-dependent polyamine-stimulated fashion in crude cell homogenates. The enzyme modification that produces this charge diversity between the alternative enzyme states was further investigated for its role in enzyme activity induction, protein stability and rapid turnover. Inhibition of new protein synthesis by cycloheximide resulted in a much more rapid loss of form I enzyme than of form II, suggesting that during normal enzyme turnover the latter enzyme state may be derived from the former. Culture conditions that favour the stabilization of this usually labile enzyme generally induced an increased proportion of the enzyme in the form II charge state. In particular, inhibitors of synthesis of spermidine and spermine induced the stabilization of cellular ornithine decarboxylase and promoted a marked accumulation in form II. Conversely, polyamines added to the cells in culture induced a very rapid loss in both forms of the enzyme, an effect that could not be attributed merely to an inhibition of new enzyme synthesis. It appears that the polyamines, but not putrescine, may be an essential part of the rapid ornithine decarboxylase inactivation process and that they may function in part by stimulating the conversion of the more stable enzyme form II into the less stable enzyme state, form I.
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PMID:Ornithine decarboxylase modification and polyamine-stimulated enzyme inactivation in HTC cells. 392 40

Antizyme reversibly inhibits ornithine decarboxylase activity by direct binding to the enzyme. The velocity of the reaction between ornithine decarboxylase and antizyme was markedly accelerated as the concentration of sodium chloride in the medium was increased and as the temperature of incubation was lowered. The equilibrium constant (binding constant) of the reaction between ornithine decarboxylase and antizyme was a little increased by decreasing salt concentrations in the medium and by decreasing the temperature of incubation.
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PMID:The velocity of the reaction between ornithine decarboxylase and antizyme highly depends on the presence of salt and temperature. 401 67

Prostaglandin E2 (PGE2) and several other prostaglandins synthesized by colon suppress the proliferative activity of colonic epithelium. However, bile salts stimulate colonic epithelial proliferation despite the actions of bile salts to enhance the release of arachidonate and consequent colonic synthesis of PGE2. The current study was conducted to assess whether bile salt-induced increases in colonic formation of arachidonate metabolites other than PGE2 were linked to the stimulation of the proliferative activity of colonic epithelium. Within 10 min of addition, deoxycholate markedly stimulated the in vitro release of [14C]arachidonate from prelabeled rat colon. When given in vivo by intracolonic instillation deoxycholate (10 mumol) increased colonic accumulation of immunoreactive prostaglandin E (PGE), thromboxane B2 (TXB2), and the lipoxygenase product 12-hydroxyeicosatetraenoic acid (12-HETE) by two to fourfold over control in 30 min. This effect of intracolonic deoxycholate was followed by a ninefold increase in mucosal ornithine decarboxylase activity (4 h), and a subsequent two to threefold increase in [3H]thymidine [( 3H]Thd) incorporation into DNA of either mucosal scrapings or isolated pools of proliferative colonic epithelial cells (24 h). Intracolonic instillation of indomethacin (50 mumol) suppressed to low or undetectable levels both basal colonic accumulation of PGE and TXB2 and the increases in each parameter induced by subsequent instillation of deoxycholate. By contrast, indomethacin enhanced accumulation of 12-HETE in both control colons and those subsequently exposed to deoxycholate. The increases in 12-HETE induced by indomethacin alone were correlated with stimulation of mucosal ornithine decarboxylase activity and [3H]Thd incorporation into mucosal DNA. Indomethacin also enhanced the increases in these parameters induced by deoxycholate. Intracolonic instillation of phenidone (25-100 mumol) suppressed accumulation of PGE, TXB2, and 12-HETE in control colons and the increases in these parameters induced by a subsequent instillation of deoxycholate. Phenidone alone did not alter mucosal ornithine decarboxylase activity or [3H]thymidine incorporation into mucosal DNA. However, phenidone suppressed or abolished increases in these parameters induced by a subsequent instillation of deoxycholate. 4-(2-[IH-imidazol-1-yl]ethoxy) benzoic acid hydrochloride UK 37,248, which selectively reduced colonic TXB2 to undetectable levels without altering PGE or 12-HETE, had no effect on control or deoxycholate-induced increases in mucosal ornithine decarboxylase activity or [3H]Thd incorporation into DNA. Neither indomethacin nor phenidone altered the increases in [(14)C]arachidonate release induced in vitro by deoxycholate. Chenodeoxycholate and cholate also stimulated [(14)C]arachidonate release from colon in vitro within 10 min, and increased colonic 12-HETE (30 min) and mucosal ornithine decarboxylase activity (4 h) upon intracolonic installation. Prior installation of phenidone inhibited the increases in both 12-HETE and ornithine decarboxylase activity induced by these bile salts. The results support a role for bile salt-induced increases in colonic accumulation of lipoxygenase products, as reflected by 12-HETE, in the subsequent stimulation of the proliferative activity of colonic epithelium.
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PMID:Bile salt stimulation of colonic epithelial proliferation. Evidence for involvement of lipoxygenase products. 643 53

The interferon (IFN)-mediated protein kinase activity in extracts from mouse L-929 cells is manifested by the phosphorylation of an endogenous 67 kD molecular weight (mw) protein in the presence of double-stranded (ds) RNA. This protein kinase activity can also be assayed after partial purification on poly(I) X poly(C)-Sepharose under phosphatase-free conditions. By the use of this latter technique, here we investigated the distribution of the protein kinase activity in different cellular compartments. Most of the protein kinase activity is found in the post-ribosomal supernatant (S100) fraction, while a small portion of it is associated with the ribosomal salt wash (RSW: 0.5 M KCl eluate of ribosomal pellet) and nuclear fractions. These results are in contrast to several observations in the literature in which the protein kinase activity is thought to be associated with the ribosomal pellet. This controversy results from the conditions used for assay of the protein kinase activity. In fact, when the kinase is assayed in crude extracts supplemented with dsRNA, very little kinase activity is detectable in the S100 fraction compared to the RSW fraction. The S100 fraction contains a high level of phosphatase(s) activity which interferes with the protein kinase assay and might account for the misinterpretation observed in the literature. Some recent results have implicated a correlation between the dsRNA-dependent protein kinase responsible for the phosphorylation of the 67 kD protein and a polyamine-dependent protein kinase which phosphorylates a similar molecular weight protein, subunit of ornithine decarboxylase (Orn Dcase). Here, we show that Orn Dcase does not bind to poly(I) X poly(C)-Sepharose and polyamines do not substitute the requirement of dsRNA for the phosphorylation of the 67 kD protein.
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PMID:Interferon-mediated protein kinase activity in different fractions of mouse L-929 cells. 650 41

(E)-Dehydro analogues of alpha-(fluoromethyl)putrescine and -ornithine derivatives were synthesized and evaluated in vitro as irreversible inhibitors of a preparation of ornithine decarboxylase (ODC, EC 4.1.1.17) obtained from rat liver. The key step in the synthesis of (E)-alpha-(fluoromethyl)dehydroornithine (17) and -putrescine (14) was the addition of propenylmagnesium bromide to fluoroacetonitrile. The resulting unstable conjugated imine salt was reduced regioselectively in situ with NaBH4 or was quenched with a solution of NaCN to give the corresponding unsaturated alpha-(fluoromethyl) amine and alpha-amino nitrile, respectively. These were transformed into 17 and 14 via a four-step sequence involving (a) phthaloyation of the amine function; (b) allylic bromination of the methyl group; (c) Gabriel reaction; and (d) hydrolytic cleavage of the protective groups. (E)-alpha-(Difluoromethyl)dehydroornithine (10) and -putrescine (7) were prepared from ethyl tert-butyl 2-(difluoromethyl)-2-(2-propenyl)malonate and di-tert-butyl 2-(difluoromethyl)-2-(2-propenyl)malonate, respectively, via a sequence similar to that reported previously for the synthesis of the saturated analogues. Compounds 17, 14, 10, and 7 proved to be much more potent enzyme-activated irreversible inhibitors of ODC than the corresponding saturated analogues. The increase in potency is particularly marked in the alpha-fluoromethyl series. The apparent dissociation constants (KI) and the times of half-inactivation of enzyme (tau 50) at infinite concentration of inhibitors are 2.7 microM and 2.6 min for 17 and 42 microM and 0.2 min for 14. The KI and tau 50 of the corresponding saturated analogues are 75 microM and 1.6 min for the ornithine derivative and 56 microM and 4.4 min for the putrescine derivative.
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PMID:alpha-(Fluoromethyl)dehydroornithine and alpha-(fluoromethyl)dehydroputrescine analogues as irreversible inhibitors of ornithine decarboxylase. 663 13

The activity of ornithine decarboxylase (EC 4.1.1.17) increased in confluent cultures of glioma C6BU-1 cells 3 h after adding a complete serum-containing medium, and was maximal 5 h later. The activity of S-adenoxyl-L-methionine decarboxylase (EC 4.1.1.50) increased soon after addition of the complete medium to the cells, and reached its peak after 11 h. The activity of diamine oxidase (EC 1.4.3.6) also increased soon after adding complete medium and was maximal 8h later, when the activity of ornithine decarboxylase reached its peak. The increase in the activity of S-adenosyl-L-methionine decarboxylase was accompanied by changes in cellular spermidine and spermine concentrations, whereas the increase in the activity of diamine oxidase was followed by the accumulation of gamma-aminobutyric acid, which was detected both in the cells and in the medium. Asparagine enhanced the utilization of radioactive putrescine by glioma cells suspended in buffered-salt/glucose solution and increased intracellular and extracellular gamma-aminobutyric acid concentrations. Radioactive putrescine was converted into spermidine and spermine by glioma cells after addition of a serum-containing medium, but not after adding buffered--salt/glucose solutions, in the presence or absence of asparagine. The kinetics of ornithine decarboxylase 'induction' and the half-life of the enzyme differed in cells incubated with buffered asparagine solutions and serum-containing media.
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PMID:Metabolism of polyamines by cultured glioma cells. Effect of asparagine on gamma-aminobutyric acid concentrations. 677 65

The responses of male noninbred rat colonic epithelial ornithine decarboxylase (EC 4.1.1.17) (ODC) and S-adenosyl-L-methionine decarboxylase (EC 4.1.1.50) (SAMD) activities following topical administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or bile salts were studied. A single intrarectal installation of 13 mumol of MNNG resulted in a significant (p < 0.001) 20-fold peak ODC activity after 4 hr, with a prompt return to control levels by 12 hr. Stimulation of SAMD activity was less pronounced but significant (p < 0.01), with a broad 2-fold peak over controls. No significant responses of colonic epithelial enzyme activities were detected following a single intrarectal instillation of N-methyl-N'-nitroguanidine, a noncarcinogenic and nonmutagenic metabolite of MNNG, at a dose equimolar to that of MNNG. Bile salts significantly (p < 0.001) induced ODC with almost the same kinetic pattern as that observed after MNNG administration in the following order: sodium deoxycholate > sodium chenodeoxycholate > sodium cholate. Activations of SAMD were similar for these 3 bile salts. Glycine- or taurine-conjugated deoxycholate showed ODC and SAMD enzyme activations similar to that of nonconjugated deoxycholate. No significant enzyme response was seen after sodium dehydrocholate treatment. Stimulation of activities of both enzymes was directly dependent on bile salt dose. Induced ODC and SAMD activities were principally localized in colonic epithelium. Deoxycholate-stimulated enzyme activities were significantly inhibited by cycloheximide. Enzyme stimulations by active compounds were accompanied by morphological changes such as mucosal cell degeneration, mucus depletion, submucosal congestion, and punctate hemorrhage, followed by submucosal leukocytic cellular infiltration. These data support the concept that initiating and promoting events may be involved in colon carcinogenesis.
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PMID:Early induction of rat colonic epithelial ornithine and S-adenosyl-L-methionine decarboxylase activities by N-methyl-N'-nitro-N-nitrosoguanidine or bile salts. 744 10

We have studied the role of mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) on salt appetite developed by deoxycorticosterone acetate (DOCA) treated rats. To this end, we measured the effects of DOCA given on alternate days on (1) salt intake; (2) MR and GR in hippocampus (HIPPO), amygdala (AMYG), and hypothalamus (HT); (3) the activity of ornithine decarboxylase (ODC), a GR-mediated response, and (4) the salt intake after treatment with the antiglucocorticoid RU 486 or the antimineralocorticoid ZK 91587. First, we demonstrated that 10 but not 1 mg DOCA induced natriogenesis. Forty-eight hours after adrenalectomy and 24 h after the last DOCA injection, 10 but not 1 mg hormone reduced binding to GR in HIPPO, AMYG, and HT. Both doses of DOCA also reduced the binding to MR in HIPPO, without changes in AMYG; in HT the 1-mg dose was without effect, but the natriogenic dose (10 mg) highly increased binding of [3H]-corticosterone to MR. Scatchard analysis demonstrated increased Bmax and Kd values in the HT of DOCA-treated rats. Occupation of GR by DOCA did not stimulate the ODC activity, in contrast to the four-fold increment effected by the glucocorticoid dexamethasone. Also, administration of RU 486 did not inhibit the sale intake promoted by DOCA, in contrast to ZK 91587 which partly delayed the natriogenic effect of DOCA. It is suggested that brain MR are involved in the natriogenic effect of DOCA, whereas the role of GR is inconclusive.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Further studies in deoxycorticosterone acetate treated rats: brain content of mineralocorticoid and glucocorticoid receptors and effect of steroid antagonists on salt intake. 775 31


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