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

---

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

We studied the effect of L-glutamine (Gln), the principal intestinal fuel, on proliferation of a porcine jejunal cell line, IPEC-J2. In cells synchronized by serum deprivation for 4 h, Gln stimulated ornithine decarboxylase (ODC; EC 4.1.1.17) in a dose- and time-dependent manner, with maximal effects at 10 mM in 3 h (P < 0.01). Similar effects were seen for the structurally related amino acid L-asparagine and serum. The Gln effect on ODC was specific, as isosmolar mannitol, glucose, methyl-beta-D-glucoside, L-phenylalanine, ammonia, and aminoisobutyric acid were ineffective. The alanine aminotransferase inhibitor aminooxyacetate (AO) inhibited the ODC stimulation by Gln in a dose-dependent manner (half-maximal inhibitory concentration = 0.5 mM). AO was not toxic to cells, as determined by propidium iodide uptake into nuclei. In addition, Gln stimulated a twofold increase of cellular 24-h [3H]thymidine incorporation above rates of control cells bathed in standard media (P < 0.01); this effect was also blocked by AO. Gln and phorbol 12-myristate 13-acetate stimulated ODC in a synergistic manner. The Na+/H+ exchange inhibitor methylisobutyl amiloride blocked the enhancement of ODC by Gln. Gln also induced the mRNA of the immediate-early gene c-jun. Gln stimulates proliferation in a porcine jejunal cell line through a mechanism requiring transamination and intact Na+/H+ exchange. This stimulation of enterocyte proliferation by Gln suggests that therapeutic Gln administration could facilitate epithelial recovery in the injured small intestine.
...
PMID:L-glutamine and L-asparagine stimulate ODC activity and proliferation in a porcine jejunal enterocyte line. 748 12

It has been shown that supraphysiological concentrations of asparagine and hypoosmotic shock stimulate ornithine decarboxylase activity in cultured cancer cells by increasing the synthesis and the half-life of the enzyme protein. Since extracellular Ca2+ is essential for the action of asparagine and is also important for cell volume regulation in certain cell types, aspects of Ca2+ physiology in asparagine-treated H-35 rat hepatoma cells were investigated. The initial rate of influx of 45Ca increased from 0.25 to 1.04 nmol/min/mg protein immediately after exposure to 10 mM asparagine. With a one-minute lag the efflux rate also increased 2.2-fold over a five minute period. Asparagine did not cause a net-gain in cellular Ca2+ as measured by 45Ca equilibration, nor did it have any effect on the cytosolic free Ca2+ as measured by Fura-2 fluorescence spectroscopy and Fluo-3 fluorescence confocal microscopy.
...
PMID:Membrane Ca2+ fluxes in rat hepatoma cells exposed to a supraphysiological concentration of asparagine. 749 52

Cimetidine has been shown to inhibit normal and carcinoma cell growth but the mechanism of the antiproliferative action is incompletely understood. The current study determined the influence of cimetidine on ornithine decarboxylase (ODC) activity, which is the initial rate-limiting enzyme in polyamine biosynthesis, in rat duodenal mucosa and IEC-6 cells (a line of normal rat intestinal crypt cells). Rats were fasted 22 hr before the various treatments and ODC activity was measured in scraped duodenal mucosa. Administration of pentagastrin and epidermal growth factor (EGF) and refeeding fasted rats significantly increased ODC activity in duodenal mucosa. Cimetidine completely inhibited increases in ODC activity in the mucosa stimulated by pentagastrin and EGF, but not by refeeding. Ranitidine and H1-receptor antagonist chlorpheniramine had similar inhibitory effects on ODC activity induced by gastrin. In cultured IEC-6 cells, cimetidine caused a linear and significant inhibition of the stimulation of ODC activity in response to pentagastrin, EGF, 5% dialyzed fetal bovine serum (FBS) and asparagine. ODC messenger RNA (mRNA) levels in IEC-6 cells were significantly increased after exposure to 5% dialyzed FBS and asparagine. Although cimetidine almost completely prevented the induction of ODC activity in IEC-6 cells exposed to serum or asparagine, the increases in ODC mRNA levels were not inhibited by the compound.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Inhibition of ornithine decarboxylase activity but not expression of the gene by cimetidine in intestinal mucosal cells. 761 40

We have previously shown that asparagine alone induces a 10-15-fold increase in ornithine decarboxylase (ODC) mRNA level in DF-40 mouse neuroblastoma cells. The induction is due to an accumulation of ODC mRNA through a post-transcriptional stabilization mechanism (Chen, Z.P. and Chen, K.Y. (1992) J. Biol. Chem., 267, 6946-6951). In the present study we showed that asparagine induced ODC gene expression in v-Ha-ras-transformed 3T3 (ras-3T3) cells but not in 3T3 cells. Other growth related genes including c-src, c-ras, and c-fos were not affected by asparagine in ras-3T3 cells. Southern blot analysis indicated that the pronounced asparagine effect was not due to ODC gene amplification in ras-3T3 cells. The effect of asparagine on the induction of ODC mRNA could account for the significant increases in the ODC activity in ras-3T3 cells. We also examined the effect of asparagine on ODC gene expression in human KD cells and their transformed counterparts. Our findings strongly suggest that the induction of ODC mRNA by asparagine may represent a component of an altered growth regulatory program associated most prominently with cell transformation.
...
PMID:Asparagine markedly induces the expression of ornithine decarboxylase gene in transformed mammalian cells but not in their untransformed counterparts. 795 61

Ornithine decarboxylase (ODC) catalyzes the first rate-limiting step in polyamine biosynthesis, and increased ODC activity is one of the earliest biochemical events associated with the induction of cellular proliferation. The current study examines the regulation of ODC activity in rat duodenal mucosa and IEC-6 cells (a line of normal rat intestinal crypt cells) in response to the trophic hormone, gastrin, and its inhibitor, secretin. Rats were fasted 22 h before the various treatments, and ODC activity was measured in scraped duodenal mucosa. Gastrin significantly increased ODC activity within 3 h to 4.3 times control levels. The effect of gastrin was totally inhibited by 5 micrograms/kg secretin. In doses of 5 or 10 micrograms/kg, secretin had no effect on basal ODC. Epidermal growth factor (EGF) and refeeding fasted rats also significantly increased ODC activity in duodenal mucosa, but the effects of EGF and refeeding were not prevented by secretin. In cultured IEC-6 cells, ODC activity was significantly increased after exposure to gastrin, 5% dialyzed fetal bovine serum (FBS), EGF, and asparagine. Secretin in doses ranging from 10(-10) to 10(-6) M caused a linear and significant inhibition of the stimulation of ODC activity by gastrin. No dose of secretin affected basal ODC activity or enzyme activity stimulated by 5% dialyzed FBS, EGF, or asparagine in IEC-6 cells. The ODC mRNA levels in IEC-6 cells were also increased after exposure to gastrin. Administration of secretin significantly prevented the stimulated expression of the ODC gene in cells treated with gastrin.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Secretin inhibits induction of ornithine decarboxylase activity by gastrin in duodenal mucosa and IEC-6 cells. 807 27

L-Glutamine (Gln) is a major respiratory fuel and substrate for nucleic acid synthesis in mammalian intestinal cells. The structurally related amino acid, L-asparagine (Asn), stimulates the proliferative enzyme ornithine decarboxylase in colonocytes, an effect that is blocked by the Na+-H+ exchange inhibitor amiloride. In an epithelial cell line derived from newborn piglet jejunum (IPEC-J2 cells), we determined intracellular pH (pHi) by computer-assisted microfluorimetry in single cells loaded with pH-sensitive dye 2',7'-bis(2-carboxyethyl)5-(6)- carboxyfluorescein. Resting pHi in N-2-hydroxyethylpiperazine-N'-2- ethanesulfonic acid-buffered NaCl Ringer was 7.06 +/- 0.02. Removal of external Na+ caused reversible acidification; recovery of pHi from NH+4-induced acid load was Na+ dependent, amiloride inhibitable, and Cl-independent. Asn and Gln had no measurable effect on resting pHi, but pretreatment with Asn or Gln induced a consistent twofold increase in pHi recovery from an acid challenge that was not seen with L-proline, D-glutamine, or L-phenylalanine. Inhibition of Gln metabolism by aminooxyacetate abolished the stimulatory effect of Gln on the exchanger. The tumor promotor phorbol 12-myristate 13-acetate (PMA) stimulated recovery rate from acid load and also increased resting pHi. The effects of PMA and Gln on Na+-H+ exchange from acid load were additive. Stimulation of Na+-H+ exchange by PMA, but not by Gln, was inhibited by protein kinase C (PKC) inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpeperazine. We conclude that Gln metabolism stimulates Na+-H+ exchange of acid-loaded porcine enterocytes by a mechanism not requiring activation of PKC.
...
PMID:L-glutamine and L-asparagine stimulate Na+ -H+ exchange in porcine jejunal enterocytes. 820 29

Ornithine decarboxylase (ODC) is the rate-limiting enzyme in polyamine synthesis and is regulated by both transcription-dependent and transcription-independent mechanisms. We compared the effects of asparagine, an amino acid previously shown to increase ODC activity in adult hippocampal slices, on ODC mRNA and activity in adult and neonatal hippocampal slices. In addition, we evaluated the effects of asparagine on ODC activity following seizure activity elicited by systemic administration of kainic acid (KA) in both adult and neonatal rats. Asparagine produced an increase in ODC gene expression and activity in both adult and neonatal hippocampal slices. The increase in ODC activity elicited by asparagine in hippocampal slices was the same in control animals as in animals sacrificed 16 h after KA-induced seizure activity. The asparagine-elicited increase in ODC activity in neonatal and adult hippocampal slices was blocked by the RNA synthesis inhibitor, actinomycin D. Finally, polyamines produced an inhibition of ODC activity in neonatal hippocampal slices. The results indicate that the regulation of the expression and activity of ODC is similar in neonatal and adult hippocampus.
...
PMID:Transcriptional activation of ornithine decarboxylase in adult and neonatal hippocampal slices. 840 82

During growth stimulation of cells, Ca2+ and amino acids of the A, ASC and N transport systems are important for the induction of ornithine decarboxylase (ODC, L-ornithine carboxylase, EC 4.1.1.17). In order to clarify the relationship between Ca2+ and amino acids, we studied the induction of ODC by asparagine under three different Ca2+ states in H-35 rat hepatoma cells. First, in normal cells, extracellular Ca2+ above 0.1 mM and 10 mM asparagine separately stimulated ODC activity and their effects were approximately additive. In these normal cells, asparagine could act in the absence of medium Ca2+. TMB-8, a sequestered-Ca2+ release antagonist, had no effect on ODC induction whilst the asparagine action is sensitive to treatment with W7, a Ca-calmodulin antagonist, or lanthanum, a Ca2+ antagonist. Secondly, in cells treated with 0.5 mM EGTA in Ca(2+)-free medium, the asparagine action on ODC induction was blocked but the inhibition could be reversed by the addition of Ca2+ to the medium. Thirdly, ionomycin treatment in the absence of medium Ca2+ did not block the asparagine effect. Furthermore, in ionomycin-treated cells, the presence of high levels of medium Ca2+ increased ODC activity, but this increase was additive to, and could not replace, the action of asparagine. Our results indicate that the asparagine action does not depend on an increase of intracellular free-Ca2+.
...
PMID:Independent actions of asparagine and high levels of free Ca2+ in the induction of ornithine decarboxylase. 843 91

Refeeding fasted rats significantly stimulates mucosal growth and ornithine decarboxylase (ODC), the rate-limiting enzyme in the biosynthesis of polyamines, but the exact mechanism responsible for induction of ODC at the molecular level is unknown. Of normal dietary constituents, the amino acid asparagine markedly increases ODC activity and mucosal growth when administered intragastrically. The current study examined the expression of the ODC gene in IEC-6 cells (a line of normal rat small intestinal crypt cells) after exposure to asparagine. Cells were grown in Dulbecco's minimal essential medium containing 5% dialyzed fetal bovine serum. They were deprived of serum for 24 h before experiments. Exposure to asparagine at the dose of 10 mM resulted in the rapid increase in ODC mRNA levels. The increased expression of the ODC gene began 1 h after and peaked between 3 and 5 h after treatment with asparagine. Maximum increases in ODC mRNA levels were approximately fivefold the normal value. Increased levels of ODC mRNA in cells exposed to asparagine were paralleled by increases in ODC protein and enzyme activity and cellular polyamine levels. The half-life of mRNA for ODC in unstimulated IEC-6 cells was approximately 30 min and increased to > 2 h in cells exposed to 10 mM asparagine. The half-life of ODC activity also was increased in asparagine-treated cells. When cellular protein synthesis was inhibited by cycloheximide, asparagine superinduced ODC mRNA levels. Furthermore, asparagine also significantly stimulated DNA synthesis in IEC-6 cells. These results indicate that 1) asparagine stimulates ODC in IEC-6 cells through multiple pathways and 2) increased ODC mRNA levels result partly from a delay in the rate of degradation. These findings suggest that luminal amino acids stimulate gut mucosal growth in association with their ability to regulate ODC gene expression.
...
PMID:Expression of the ornithine decarboxylase gene in response to asparagine in intestinal epithelial cells. 876 Jan 20

L-Asparagine stimulates bi-directional Ca(2+) flows and induces ornithine decarboxylase in Reuber H-35 hepatoma cells. Previously it has been shown that these effects are completely, but reversibly inhibited by lanthanum chloride. In this study we examined the role(s) of Ca(2+) flows using more specific Ca(2+) flow inhibitors. It was shown that ornithine decarboxylase induction was inhibited by CdCl(2) and verapamil at concentrations above 1 mu M and 100 mu M respectively, but was unaffected by as much as 300 mu M NiCl(2), 1 mM nifedipine, or 10 mu M omega-conotoxin. Enzyme induction was blocked by the Ca(2+)-ATPase pump antagonists vanadate and Compound 48/80 in a dose-dependent manner. These results, taken together with the observations that extracellular Ca(2+) is essential for enzyme induction but a substantial elevation of cytoplasmic [Ca(2+)] is not, suggest that Ca(2+) inflow independent of the receptor-activated Ca(2+) channels, and the Ca(2+)-ATPase mediated Ca(2+) out-flow, are both important factors in the action of L-asparagine.
...
PMID:Characterization of Ca(2+) flows essential in ornithine decarboxylase induction by L-asparagine in rat hepatoma cells using Ca(2+) flow inhibitors. 913 51


<< Previous 1 2 3 4 5 Next >>

---