Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.1.17 (ornithine decarboxylase)
 6,351 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Histamine and putrescine (a precursor of polyamines) are formed by histidine decarboxylase (HDC) and ornithine decarboxylase (ODC), respectively. Within a few hours after injection of a lipopolysaccharide (LPS) into mice, HDC is induced in the liver, spleen, lung and bone marrow, and ODC is induced in the liver, spleen and bone marrow. Since LPS is known to stimulate the production of various cytokines, the abilities of various cytokines to induce HDC and ODC in the tissues of mice were examined. IL-2, IL-6, IL-8, IFN gamma and M-CSF were ineffective. IL-1 alpha, IL-1 beta, TNF alpha and TNF beta induced HDC and ODC, as does LPS. On the other hand, GM-CSF and G-CSF induced HDC and ODC only in the spleen and bone marrow within a few hours after their injection. These results suggest that, in addition to their roles in inflammation or immune responses, HDC and ODC are also involved in an early stage of hematopoiesis.
 ...
PMID:GM-CSF and G-CSF stimulate the synthesis of histamine and putrescine in the hematopoietic organs in vivo. 138 20

The subclone M-07e, derived from the interleukin-3 (IL-3)-responsive human myeloid cell line M-07, is strictly dependent on either IL-3 or granulocyte-macrophage-colony-stimulating factor (GM-CSF) for its growth and survival. This cell line may be regarded as a candidate model to investigate the poorly understood events triggered by growth factors binding to human hemopoietic cells. Both IL-3 and GM-CSF induce in M-07e cells an increase of ornithine decarboxylase (ODC) activity, which reaches its maximum at 24-30 h and fully depends on de novo protein synthesis. The growth factors do not elicit translocation of protein kinase C to the membrane; thus a role of the kinase in ODC induction is ruled out. An amiloride-inhibitable Na+/H+ exchanger is present in the membrane of M-07e cells; its apparent Km for extracellular Na+ is 47.77 mM; and its activity is greatly enhanced when the cytoplasm is acidified. Growth-factor-evoked ODC activation and DNA synthesis are blocked in a dose- and time-dependent manner when M-07e cells are incubated with ethylisopropylamiloride, a specific inhibitor of Na+/H+ exchanger. The exchanger does not appear to be directly activated by IL-3 or GM-CSF, but its operation is strictly required for the biological effects of these growth factors on M-07e cell line.
 ...
PMID:Evidence for a role of the Na+/H+ exchanger in the colony-stimulating-factor-induced ornithine decarboxylase activity and proliferation of the human cell line M-07e. 217 Apr 28

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.
 ...
PMID:Characterization of lipopolysaccharide-induced macrophage gene expression. 245 94

Colony-stimulating factors (CSFs) stimulate the activation and steady-state mRNA accumulation of an important regulatory enzyme for macromolecular synthesis, ornithine decarboxylase (ODC). Cloned murine CSF-dependent cell lines exhibited a rapid activation of ODC enzyme activity, detectable within ten minutes of stimulations with either interleukin-3 (IL-3), GM-CSF, or G-CSF. This early phase of enzyme activation did not require early protein or mRNA synthesis. The subsequent protracted rise in ODC activity occurring four to six hours after CSF treatment was dependent on increases in steady-state ODC mRNA accumulation and de novo protein synthesis. CSF, therefore, modulates both posttranslational activation of preexisting ODC and stabilization and accumulation of ODC mRNA. Antiproliferative signals, such as cAMP or interferon-gamma (IFN-gamma), effectively inhibited the CSF-directed increase in steady-state ODC mRNA. Cotreatment of the murine NSF 60.8 cell line with IFN-gamma and GM-CSF decreased steady-state ODC mRNA greater than 80% as compared with GM-CSF-treated cells alone. IFN treatment did not cause any appreciable destabilization of mature ODC mRNA, suggesting that its major effect may be at the level of ODC mRNA transcription or posttranscriptional processing. These data indicate that the ODC gene-protein system is an important molecular locus of the effects of myeloid proliferative and antiproliferation signals.
 ...
PMID:Myeloid growth factor(s) regulation of ornithine decarboxylase: effects of antiproliferative signals interferon-gamma and cAMP. 246 92

The polypeptide hormones governing the proliferation and differentiation of the mature immune system and hematopoiesis are collectively referred to as lymphokines. We have examined a number of biochemical and molecular events stimulated by several unique lymphokines which exhibit proliferative activity on lymphoid and myeloid cell lines. Interleukin-2 (IL-2) and several members of the colony-stimulating factors (IL-3, G-CSF, and GM-CSF) stimulate similar patterns of cellular phosphorylation including the prominent phosphorylation of a 68-kDa substrate present in numerous distinct lineage cell lines. The 68-kDa substrate is phosphorylated by protein kinase C on threonine residues and is primarily cytosolic. Another kinase system activated by either physiological ligand or synthetic diacylglycerol phosphorylated the 40S ribosomal protein in a dose-dependent manner. The increased phosphorylation of S6 protein was associated with enhanced chain elongation in vitro. The kinase responsible for the in situ phosphorylation, however, was not protein kinase-C (PK-C) but another physicochemically distinct Mg2+-dependent enzyme (termed S6 kinase). These studies suggested that, although PK-C was activated by diacylglycerol, another kinase, S6 kinase, was the effector enzyme involved in the phosphorylation of the 40S protein. IL-2 and all other CSFs tested stimulated the transcription of the nuclear protooncogenes c-fos, c-myc, and c-myb. In addition, ornithine decarboxylase mRNA accumulation was also stimulated. Phorbol esters also stimulated similar gene expression; however, cyclic AMP analog inhibited phorbol ester or ligand-induced c-myc expression and ODC mRNA accumulation. Cyclic AMP agonists are antiproliferative to all the growth factors tested. We have constructed complementary oligonucleotides, "antisense", against c-fos, c-myc, and other structural genes induced by the growth factors. Such antisense oligomers were capable of selectively deleting protein expression of the respective gene products and inhibited the biological action of the growth factors.
 ...
PMID:The molecular basis of immune cytokine action. 265 49

Haemopoietic growth factors stimulate a number of consensus biochemical and molecular events regardless of the specificity detailed by unique ligand and receptor structures. Analysis of three distinct colony stimulating factors, CSFs (IL-3, G-CSF, GM-CSF) and the lymphocytotropic growth factor IL-2 reveal remarkable similar distal subcellular biochemical signals although initial membrane 'signal transduction' may differ significantly. Both early progenitor cell growth factors, such as IL-3, and late acting factors such as CSF-1, stimulate tyrosine and serine-threonine substrate phosphorylations. One substrate (p68) is phosphorylated by many CSF stimulants, including IL-2, suggesting a highly conserved role in many unique receptor(s) signal transduction processes. The proliferative CSFs and IL-2 also stimulate the expression of many of the same genes including proto-oncogenes, ornithine decarboxylase and members of the ancient family of stress response genes. Although initial membrane events may differ among the respective proliferative stimulants, biochemical and molecular convergence on highly conserved cellular substrates and the programme of gene expression is seen.
 ...
PMID:Molecular events associated with the action of haemopoietic growth factors. 327 Apr 54