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)

The regulation of ornithine decarboxylase (ODC) was examined in an intestinal epithelial crypt cell line (IEC-6). Addition of fetal bovine serum or growth factors to quiescent preconfluent cells resulted in a 20- to 30-fold increase in the specific activity of ODC, which was maximal at approximately 4 h. In contrast, ODC mRNA levels either did not change or increased only twofold over the time period examined. The increased enzymatic activity was blocked by cycloheximide, putrescine, and the calmodulin antagonist N-(6-aminohexyl)-5-chloro-1-napthalinesulfonamide (W-7). Cycloheximide alone increased mRNA levels and potentiated the induction in response to serum, suggesting that protein synthesis is not required for the increase in mRNA accumulation. In contrast to its effect on ODC activity, W-7 was without effect on the serum-stimulated increase in ODC or c-fos mRNA levels. Putrescine decreased ODC activity, but not mRNA content, in a dose-dependent manner with an IC50 between 0.1 and 1.0 microM. Also, serum stimulation resulted in a threefold increase in the stability of the enzyme in the presence of cycloheximide; this effect was blocked by pretreatment with W-7. Enzymatic activity was paralleled by ODC protein content as determined by [3H] difluoromethylornithine binding. Finally, the induction of enzyme activity was due entirely to an increase in Vmax as no detectable change in Km for ornithine was detected. These results suggest that ODC is regulated at multiple levels by independent signaling pathways in cultured intestinal epithelial cells. Increased levels of active ODC protein and enzymatic activity are sensitive to W-7 and putrescine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Multiple pathways for the regulation of ornithine decarboxylase in intestinal epithelial cells. 210 56

Steady-state levels of messenger RNA (mRNA) for different members of the heat-shock protein 70 gene family were studied in rat livers reperfused after non-necrogenic ischemia. The expression of constitutive hsc 73 gene decreases during ischemia, returns to normal upon reperfusion, and increases 4 hr after restoration of blood flow. Reperfusion induces the expression of another hsp 70 gene family member (the so-called inducible hsp 70 gene), which remains at high levels for at least 7 hr. The induction of hsp 70 family genes is preceded by activation of the cellular oncogene c-fos, the most prompt change in gene expression detected in reperfused liver. Run-on experiments demonstrate that the increased expression of these genes is largely dependent on activation of transcription. Changes in the amount of c-myc and ornithine decarboxylase mRNA are not evident, while the level of the mRNA for glucose-regulated protein GRP 78 increases later, concurrent with the onset of the acute phase response to surgical trauma. Analysis of polysomal and nonpolysomal fractions from sucrose gradients indicates that in postischemic liver, hsp 70 and hsc 73 mRNA are rapidly engaged on light polysomal or nonpolysomal complexes and are later shifted to polysomes. Albumin mRNA displays the same behavior, indicating that hsp 70 mRNA are not preferentially translated and that increased transcription is the major mechanism for enhanced hsp synthesis in postischemic liver. Damage by active oxygen species, pressure overload, and derangements of protein synthesis is likely to include the causative factors of increased expression of c-fos and the hsp 70 gene family in postischemic reperfused liver.
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PMID:Reprogramming of gene expression in postischemic rat liver: induction of proto-oncogenes and hsp 70 gene family. 210 73

Genes of higher eucaryotic cells are considered to show only a limited response to nutritional stress. Here we show, however, that omission of a single essential amino acid from the medium caused a marked rise in the mRNA levels of c-myc, c-jun, junB and c-fos oncogenes and ornithine decarboxylase (ODC) in CHO cells. There was no general accumulation of mRNAs in amino acid-starved cells, since the gamma-actin, beta-tubulin, protein kinase C, RNA polymerase II, and glyceraldehyde-3-phosphate dehydrogenase mRNAs and the total poly(A)+ mRNA were not increased. The levels of c-myc, ODC, and c-jun mRNAs were elevated more by amino acid starvation than by inhibition of protein synthesis with cycloheximide, which is known to increase the levels of these mRNAs. Importantly, however, cycloheximide present during amino acid starvation reduced the rise in the levels of the mRNAs down to the level obtained with cycloheximide alone. This implies that protein synthesis is required for the accumulation of c-myc, ODC, and c-jun mRNAs in amino acid-deprived cells. The junB and c-fos mRNAs, instead, were increased to the same extent or less by amino acid starvation than by cycloheximide treatment. The accumulation of the c-myc mRNA in amino acid-starved cells was due to both stabilization of the mRNA and increase of its transcription. The rise in the c-jun mRNA level seemed to be caused merely by stabilization of the mRNA. Further, despite the inhibition of general protein synthesis, amino acid starvation led to an increase in the synthesis of c-myc polypeptide. The results suggest that mammalian cells have a specific mechanism for registering shortages of amino acids in order to make adjustments compatible with cellular growth.
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PMID:Deprivation of a single amino acid induces protein synthesis-dependent increases in c-jun, c-myc, and ornithine decarboxylase mRNAs in Chinese hamster ovary cells. 212 33

A single electroconvulsive shock (ECS) resulted in a major induction of cerebral ornithine decarboxylase (ODC) mRNA and a rapid and transient elevation of ODC enzyme activity. The proto-oncogene c-fos was also transiently induced under the same conditions. Following a rapid rise in mRNA levels, the messages for these proteins take different courses. The c-fos mRNA fell to below control levels by 1 h, while the ODC mRNA remained elevated beyond 24 h. The ECS-induced elevation of ODC enzyme activity was not abolished by adrenalectomy but was attenuated significantly by the anti-convulsant MK-801. These results imply that the induction of cerebral ODC may be neuronal activity dependent, and suggest that the ODC/polyamine system may be linked to the proposed third messenger cascade, involving c-fos, which couples cell stimulation to gene expression, resulting in long-term adaptive responses.
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PMID:Electrically stimulated rapid gene expression in the brain: ornithine decarboxylase and c-fos. 215 84

The rat pheochromocytoma cell line (PC-12) offers a powerful in vitro model to study the mechanism of growth factor-induced differentiation and proliferation. Within minutes of addition, agents such as nerve growth factor (NGF), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) and dibutyryl cyclic AMP (db cAMP) rapidly activate cellular immediate early genes such as c-fos, c-jun, jun-B, and egr-1. fra-1, a member of the immediate early gene family, follows a distinctly later time course of induction than c-fos, c-jun, jun-B, and egr-1, suggesting that fra-1 may attenuate the action of genes induced earlier. We demonstrate that constitutive expression of fra-1 in PC-12 cells results in pronounced inhibition of NGF-induced differentiation. Transcriptional activation of c-fos, c-jun, jun-B, and egr-1 by NGF, EGF, and db cAMP was down-regulated to a varying extent whereas NGF-induced ornithine decarboxylase (ODC) was not affected. Expression of jun-D was not affected in PC-12 fra-1 cells. Transfection of fos and egr-1 promoter-chloramphenicol acetyl transferase (CAT) plasmid into these stable fra-1-expressing PC-12 cells revealed that repression of fos and egr-1 was exerted at the promoter level. Thus deregulated fra-1 expression may inhibit PC-12 cell differentiation by altering the patterns of immediate early gene expression.
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PMID:Inhibition of PC-12 cell differentiation by the immediate early gene fra-1. 217 37

The G0S19 genes are members of the "small inducible" family of genes, which have similar exon-intron organizations and encode secreted proteins with similar dispositions of cysteine and proline residues. G0S19-1 mRNA is increased shortly after the addition of lectin or cycloheximide to cultured human blood mononuclear cells. The cDNA sequence is homologous to that of a murine gene encoding an inhibitory cytokine (MIP1 alpha/SCI), which decreases hemopoietic stem cell proliferation. The homology extends to the 3' noncoding region, which contains two conserved elements: (i) GGGACTCTTC, a potential transcription factor NF chi B-binding site, and (ii) TTTTGTAATTTATTTT, which is found in some related genes (e.g., that encoding the immediate early protein ornithine decarboxylase). A similar but complementary sequence is present in human immunodeficiency virus. Two of the three human genes that hybridize to G0S19-1 cDNA were sequenced. G0S19-1 has 5' AP1-like recognition elements as found in some other phorbol ester-responsive genes (e.g., c-fos). G0S19-2 has a 5' Alu sequence, but is likely to be expressed because of the conservation of sections of the gene believed to be important for function. The 5' flanks of both genes contain the nucleotide motifs CK-2 and SRE, indicating cytokine-like genes with the potential to respond to growth factors. G0S19-1 is the main G0S19 gene expressed in adult T lymphocytes and may encode a homeostatic negative regulator of the size of cell populations (or subpopulations) which are derived ultimately from marrow stem cells. As such, it is a potential antioncogene.
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PMID:Three human homologs of a murine gene encoding an inhibitor of stem cell proliferation. 227 Nov 20

A temperature-sensitive cell-cycle mutant, tsJT16, which has been isolated from Fischer rat fibroblasts, was defective in the function(s) that operated soon after growth stimulation. When G0-arrested tsJT16 was stimulated to proliferate, it entered the S phase after 12-15 h at 34 degrees C but failed to do so at 40 degrees C. The function mutated in tsJT16 was required to be normal for the first 4 h or less for cells to transit from the G0 to S phase. The induction of cell-cycle-dependent genes such as c-fos, c-myc and ornithine decarboxylase was observed at both temperatures after growth stimulation. Although an increase in total protein synthesis occurred at both temperatures after growth stimulation, synthesis of one protein (p70) (pI 7.8 and Mr 70,000) was inhibited at 40 degrees C. Synthesis of p70 was negligible in G0-arrested cells and blocked by actinomycin D in serum-stimulated cells at 34 degrees C. These results suggest that tsJT16 has a ts defect in one of the signal transduction processes to induce gene activation. tsJT16 was also defective in progression of the G1 phase of growing cells, consistent with the previous results in which growth stimuli were required at G1 for continuation of proliferation.
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PMID:A temperature-sensitive cell-cycle mutant of mammalian cells, tsJT16, is defective in a function operating soon after growth stimulation. 234 May 88

The mechanisms responsible for ethanol-associated inhibition of liver regeneration are poorly understood but may involve the modulation of protooncogene expression. To test this hypothesis, the steady-state messenger RNA levels of several protooncogenes involved in cellular proliferation were measured in livers obtained from ethanol-fed rats and isocalorically maintained controls before and during surgically-induced liver regeneration. Regeneration was significantly inhibited in ethanol-fed rats as evidenced by delayed induction of ornithine decarboxylase activity and reduced thymidine incorporation, mitotic index, and restoration of liver mass after partial hepatectomy. As previously reported, partial hepatectomy induced the time-dependent expression of mRNA for c-fos, c-myc, and c-Ha-ras. However, the transcript levels of these protooncogenes were indistinguishable in ethanol and control livers at various time points between 0-72 hours after partial hepatectomy. Although regeneration after partial hepatectomy is significantly delayed in ethanol-fed rats, the transcription of certain protooncogenes, which encode for both DNA-binding and signal-transducing proteins, appears to proceed normally. Consequently, ethanol-associated impairment of liver regeneration cannot be explained by altered transcription of these protooncogenes. The results suggest that either the expression of these protooncogenes alone may not be sufficient to trigger liver regeneration or that ethanol inhibits protooncogene-mediated events at posttranscriptional levels.
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PMID:Ethanol inhibits liver regeneration in rats without reducing transcripts of key protooncogenes. 239 31

The G0/G1 to S transition in quiescent BALB/c 3T3 cells stimulated by serum growth factors can be specifically blocked by the administration of interferon (IFN) to the system. In the present communication, we studied whether IFN inhibits the early events in the G0/G1 phase that are initiated by the platelet-derived growth factor (PDGF). The results show that IFN inhibits most of the PDGF-mediated increase of c-myc, ornithine decarboxylase, and beta-actin mRNAs measured 3 hr after stimulation. c-fos mRNA levels are reduced by IFN as early as 20 min after exposure of the quiescent cells to PDGF. The expression of several genes that belong to the competence gene family is, therefore, inhibited by IFN and this could account for the failure of the IFN-treated cells to enter into the S phase when growth factors present in the platelet-poor plasma are added. We also report that the PDGF-mediated increase in the uptake of deoxyglucose is not impaired by IFN, thus suggesting that the early effects of IFN on gene expression do not result from inhibition of binding of PDGF to its cell-surface receptors. Unlike the direct stimulatory effect of PDGF, which is not sensitive to cycloheximide, the inhibitory effect of IFN on c-myc mRNA levels depends in part on protein synthesis. We propose that a putative product of one of the IFN-induced genes could mediate the decrease in expression of the PDGF-regulated gene family.
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PMID:Inhibitory effects of interferon on the expression of genes regulated by platelet-derived growth factor. 241 66

A cDNA library from LPS-treated murine peritoneal macrophages has been screened by differential hybridization with radiolabeled cDNA from untreated and LPS-treated macrophages. Six clones hybridizing with mRNA sequences present in LPS-treated cells but not in controls were selected for further characterization. When the recombinant bacteriophage DNA from each clone was used as a probe in Northern analysis of total RNA from LPS-treated macrophages, inducible mRNA ranging from 1.45 to 6.4 kb were seen. In five of six cases, the mRNA expression was undetectable in untreated macrophage cultures. All but one clone identified mRNA that were inducible even in the presence of cycloheximide, indicating the independence of such gene expression from protein synthesis; none of the genes were superinduced by this treatment. The time course of expression differed among the individual genes. Four were induced transiently, whereas two showed stable increasing accumulation through an 8-h period after stimulation. In addition, four of the genes were seen within 30 min of stimulation, whereas two were seen only after 2 to 4 h. Two genes were induced only by treatment with LPS, whereas four were also induced in response to other agents, including IFN-gamma, macrophage CSF, and PMA. The insert sequences from these recombinant clones did not hybridize with a set of cDNA encoding other inducible gene products, including TNF, IL-1, ornithine decarboxylase, c-myc, c-fos, JE, or KC. Thus, these six cDNA appear to encode inducible macrophage genes that are distinct from one another as well as from a selection of previously described early genes. Although their functional identity remains indeterminate, they may encode previously described early proteins induced in macrophages treated with LPS.
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PMID:Characterization of lipopolysaccharide-induced macrophage gene expression. 245 94


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