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)

CD45 is a transmembrane tyrosine-specific phosphatase which participates in lymphoid cell signal transduction during T cell activation, as well as in intrathymic negative and positive selection. In mammals, this molecule exhibits a variety of isoforms of different molecular weight, whose roles have still to be fully elucidated. We report here that apoptosis of rat thymocytes after in vitro dexamethasone and heat shock treatment was accompanied by an early significative increase of cells expressing CD45RC, the high molecular weight isoform of CD45 molecule. The same phenomenon was observed in thymocytes derived from in vivo dexamethasone-treated rats. However, the increase of CD45RC+ cells was not apparently characteristic of cells undergoing apoptosis, as the same phenomenon was also observed in rat thymocytes induced to proliferate by Concanavalin A. On the whole, these results suggest that CD45 modulation can be added to the list of early molecular events, such as the increased expression of genes (ornithine decarboxylase), proto-oncogenes (c-fos, c-jun, c-myc) and activation of transcription factors (AP-1, NFkB), we previously demonstrated in the same experimental model to occur and to be shared by these two apparently opposite biological processes, i.e., cell proliferation and apoptosis, both likely depending on a complex balance of protein phosphorylation and dephosphorylation.
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PMID:Involvement of CD45 in dexamethasone- and heat shock-induced apoptosis of rat thymocytes. 757 67

Ornithine decarboxylase (ODC), the first and rate-limiting enzyme of polyamine metabolism, has been shown to be required for entry into and progression through the cell cycle. However, the role of ODC and polyamines in apoptosis remains to be determined. We have examined ODC expression and polyamine levels in thymocytes activated to undergo apoptosis by dexamethasone treatment. We have demonstrated a rapid and reversible induction of ODC (mRNA and activity), as previously reported for the mRNA expression of other "early" genes, c-fos, c-jun, and c-myc, in the same experimental model. Surprisingly, polyamine levels diminished progressively starting at 2-4 h after dexamethasone treatment, and spermine was depleted at 8-12 h. This seemed to be relevant since increasing the intracellular polyamine levels by exogenous spermine administration prevented the DNA "laddering" (2-4 h) and the DNA loss from the nucleus (8-18 h) due to dexamethasone treatment. Moreover, the activities of spermidine/spermine N1-acetyltransferase, which controls the cytosolic polyamine interconversion pathway, and of spermidine N8-acetyltransferase, which regulates the nuclear pool and functions of polyamines, were measured in apoptotic cells. Spermidine/spermine N1-acetyltransferase activity progressively increased and might be responsible for spermidine and spermine excretion as acetyl derivatives. In contrast, spermidine N8-acetyltransferase activity remained unchanged. A completely different scenario was observed in proliferating concanavalin A-treated thymocytes, studied for comparison. In this case, polyamine levels increased, remaining at high values until 12 h. This is likely a consequence of the rapid and prolonged induction of ODC (mRNA and activity), accompanied by that of spermidine/spermine N1-acetyltransferase (mRNA and activity).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Involvement of ornithine decarboxylase and polyamines in glucocorticoid-induced apoptosis of rat thymocytes. 764 33

The AP-1 consensus sequences (TGAGTCA) are the major 12-O-tetradecanoylphorbol113-acetate (TPA) responsive elements shared by several TPA inducible genes, such as c-sis, c-fos, c-myc, collagenase, stromelysin, hMTIIA and SV40. However, the role of AP-1 binding sites, which are present in the introns 3, 5, and 11 of ODC gene, in the regulation of TPA-induced ornithine decarboxylase (ODC) gene transcription are unknown. We determined the TPA responsiveness of the AP-1 sequences in the introns of ODC gene in CV-1 cells which induce ODC activity and mRNA in response to TPA treatment. ODC introns containing AP-1 sequences were inserted into the chloramphenicol acetyltransferase (CAT) reporter gene. Transient transfection of CV-1 cells with the intron-CAT constructs followed by TPA treatment did not induce CAT activity. However, when flanking regions of the AP-1 site in intron 3 were narrowed down to 74 bp, TPA induced CAT activity by 5- to 7-fold. The TPA-inducibility could be eliminated by mutation of the AP-1 site (TGAGTCA-->TGATGCCA or TGATGA) in 74 bp of intron 3. These results indicate that the AP-1 sequences in the intact ODC introns may not be responsive to TPA. The flanking sequences of the AP-1 site may be crucial to determine whether the AP-1 site is accessible to the TPA-induced transcriptional factor(s).
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PMID:Lack of 12-O-tetradecanoylphorbol-13-acetate responsiveness of ornithine decarboxylase introns which have AP-1 consensus sequences. 765 80

Neurotransmitters act as trophic factors during brain development, regulating expression of genes that control cellular differentiation. One example of this trophism is the beta adrenergic signaling cascade: activation of beta receptors leads sequentially to increased cyclic AMP (cAMP), augmented expression of the nuclear transcription factor, c-fos, and induction of ornithine decarboxylase (ODC), an enzyme obligatory for neuronal development. After neonatal lesioning of noradrenergic nerves with 6-hydroxydopamine (6-OHDA), beta receptors become uncoupled from ODC induction in the cerebellum, a region that undergoes its peak of cell replication/differentiation postnatally. The present study investigates the mechanism for uncoupling of beta receptors from response elements. In the cerebellum, 6-OHDA had minor effects on beta receptor binding capabilities and caused slight supersensitivity of the beta adrenergic response of adenylate cyclase; the latter reflected increased expression of cyclase catalytic subunits, rather than a specific effect on beta receptor coupling. In contrast, the linkage of cAMP to cerebellar c-fos expression showed marked deficiencies in lesioned animals and a corresponding loss of the ability of beta receptors to induce c-fos; accordingly, this is a likely point at which beta adrenergic control of ODC is programmed by neuronal input. A critical period exists for neurotrophic influence: the alterations persisted past the point at which cerebellar norepinephrine levels recovered, and comparable effects did not occur in earlier-developing regions. In the forebrain, for example, neonatal lesions produced receptor upregulation and supersensitivity of c-fos to cAMP stimulation. These results suggest that presynaptic input is vital in programming beta adrenergic responsiveness during a critical period of development, and that interruption of transsynaptic events occurring at this time can lead to lasting alterations in neuronal differentiation and responsiveness.
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PMID:Role of presynaptic input in the ontogeny of adrenergic cell signaling in rat brain: beta receptors, adenylate cyclase and c-fos protooncogene expression. 771 97

PRL has been shown to induce a number of genes after the stimulation of quiescent Nb2 T-cells, including c-fos, c-myc, ornithine decarboxylase, interferon regulatory factor-1, and others. One of these genes, LHRH, has not previously been reported to respond in this manner, although we and others have reported its presence in rat and human T- and B-cells. Furthermore, recent evidence suggests that LHRH functions as an immunoregulator in a cytokine-like manner. Using the rat immature T-cell line Nb2, we present data showing for the first time that 1) the LHRH gene is regulated by PRL at various times during the cell cycle; 2) an alternatively spliced LHRH messenger RNA exists in Nb2 cells and may produce a new truncated GnRH-associated peptide (alternatively called PIF for PRL-inhibiting factor); 3) the LHRH receptor is expressed in lymphocytes in a manner similar to the LHRH gene after PRL addition, and its complementary DNA sequence is identical to that of the pituitary receptor; 5) the SH gene, found on the opposite strand of the LHRH gene, is expressed in lymphocytes at the same time and in the same manner as the LHRH gene; 6) the LHRH messenger RNA has a very short half-life in these cells; and 7) the lymphocyte LHRH transcription start site is essentially the same as the hypothalamic site. These data strengthen the relationship between PRL and LHRH expression in the immune system and further support our contention that LHRH is an important immunoregulator, on par with other known cytokines.
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PMID:Coordinate gene expression of luteinizing hormone-releasing hormone (LHRH) and the LHRH-receptor after prolactin stimulation in the rat Nb2 T-cell line: implications for a role in immunomodulation and cell cycle gene expression. 776 Aug 50

Nerve growth factor (NGF) induced differentiation of primary and permanent neuronal cell cultures is accompanied by a rapid and transient induction of ornithine decarboxylase (ODC) mRNA and enzymatic activity; a similar ODC induction accompanies mitogenic effectors in many additional cell types. In an effort to assess the role of ODC activity in neuronal cell biology, we have used the ODC suicide substrate inhibitor difluoromethylornithine (DFMO) to select PC12 cell variants with altered ODC expression patterns and characterized the resulting phenotypes. The variants fall into three distinct classes based upon their patterns of ODC mRNA and ODC activity levels; however, all are severely compromised in their ability to respond properly to NGF treatment. Following NGF treatment, none of the variants exhibits any morphological differentiation. In addition, none of the variants is capable of properly inducing either c-fos mRNA (an "immediate early" response) or GAP-43 mRNA (a "late" response) following NGF treatment. Our data suggest that altered ODC metabolism can lead to inactivation of element(s) active very early in the normal NGF signal transduction cascade.
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PMID:PC12 variants with altered ornithine decarboxylase expression patterns exhibit altered signal transduction capabilities. 781 37

This study was undertaken to assess the effects of a single or two sequential topical applications of 12-O-tetradecanoylphorbol-13-acetate (TPA) on the expression of c-fos, c-jun, junB, c-myc, and ornithine decarboxylase (ODC) in promotion-sensitive SSIN mice and the relatively promotion-resistant C57BL/6 strain. Northern blot analysis demonstrated that a single promoting dose of TPA induced ODC mRNA expression 10- to 15-fold in both strains. Treatment of each strain with a second dose of TPA, 48 h (in C57BL/6 mice) or 72 h (in SSIN mice) after the first, led to hyperinduction of ODC activity. Although this involved transcription of new ODC mRNA, the hyperinduction of ODC enzyme activity was primarily posttranscriptional. Induction of c-fos mRNA or protein was maximal about 3 h after a single treatment in either strain but was sustained for at least 6 h in C57BL/6 mice. In contrast, two treatments of SSIN mice with TPA caused a rapid, strong c-fos induction 1-2 h after treatment, whereas C57BL/6 mice responded no more strongly than after a single treatment. c-jun mRNA and protein were induced only slightly in either strain, but junB was induced about fivefold in SSIN mice and tenfold in C57BL/6 mice. Although c-myc was induced to comparable levels in both strains, the response was more prolonged in C57BL/6 mice. Compared with SSIN mice, C57BL/6 mice responded to TPA treatment, in general, with changes in proto-oncogene mRNA to a higher level or for longer or both. Thus, although small differences in the expression of these genes were observed, they were not positively correlated with the differential sensitivity of SSIN and C57BL/6 mice toward tumor promotion by phorbol esters, with the possible exception of c-fos.
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PMID:Expression of epidermal ornithine decarboxylase and nuclear proto-oncogenes in phorbol ester tumor promotion-sensitive and -resistant mice. 781 61

WI-38 cells can remain quiescent for long periods of time and still be induced to reenter the cell cycle by the addition of fresh serum. However, the longer these cells remain growth arrested, the more time they require to enter S phase. This prolongation of the prereplicative phase has been localized to a point early in G1, after the induction of "immediate early" G1 genes such as c-fos and c-jun but before maximal expression of "early" G1 genes such as ornithine decarboxylase (ODC). Understanding the molecular basis for ODC mRNA induction can therefore provide information about the molecular events which regulate the progression of cells out of long-term quiescence into G1 and subsequently into DNA synthesis. Studies utilizing electrophoretic mobility shift assays (EMSA) of nuclear extracts from short- and long-term quiescent WI-38 cells identified a region of the human ODC promoter at -491 bp to -474 bp which exhibited a protein binding pattern that correlated with the temporal pattern of ODC mRNA expression. The presence of a CACGTG element within this fragment, studies with antibodies against c-Myc and Max, the use of purified recombinant c-Myc protein in the mobility shift assay, and antisense studies suggest that these proteins can specifically bind this portion of the human ODC promoter in a manner consistent with growth-associated modulation of the expression of ODC and other early G1 genes following prolonged quiescence. These studies suggest a role for the c-Myc/Max protein complex in regulating events involved in the progression of cells out of long-term quiescence into G1 and subsequently into S.
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PMID:Regulation of human ornithine decarboxylase expression following prolonged quiescence: role for the c-Myc/Max protein complex. 782 33

tsJT16 is a cell-cycle temperature-sensitive (ts) mutant derived from rat fibroblasts whose functional defect appears soon after the growth stimulation from G0 phase. In addition to c-fos, c-myc and ornithine decarboxylase gene, 7 primarily inducible genes, c-jun, KC, JE, 2F1, 2A9, egr-1, and egr-2, were further shown to be expressed after serum stimulation at both permissive and nonpermissive temperatures. However, expression of secondarily inducible genes, cyclin D1 and D3 and cdk2, was ts and was cycloheximide sensitive. Expression of cyclin C was not inhibited by cycloheximide but it was ts. Failure in expression of G1 cyclins and Cdk2 is suggested to be a causal event for inability of growth induction of tsJT16 at the nonpermissive temperature.
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PMID:tsJT16, a cell cycle ts mutant of rat fibroblast defective in early G0/G1 transition, fails to induce G1-cyclin and cdk2 genes after serum stimulation at the nonpermissive temperature. 785 Aug 96

Here we summarize the data on 55 compounds tested in in vivo short-term assays for tumor-initiating and tumor-promoting activity in the glandular stomach of male Fischer (F344) rats. Most of the data has been previously published. Tumor-initiating activity was assayed by measuring the induction of unscheduled DNA synthesis (UDS) and DNA single strand scission; tumor-promoting activity was assayed by measuring the induction of ornithine decarboxylase (ODC) activity, increased replicative DNA synthesis (RDS), and of c-fos and c-myc oncogene expression. The compounds were orally administered. Twenty-nine compounds were tested for UDS. Eight were positive, including 5 glandular stomach carcinogens; 16 were negative, including 5 liver carcinogens; and 5 were equivocal. Twenty compounds were tested for DNA single strand scission. Twelve were positive, including 6 glandular stomach carcinogens; 7 negative, including 2 liver carcinogens; and 1 was equivocal. Thirty-two compounds were tested for RDS. Twenty-six were positive, including 8 glandular stomach carcinogens and 6 glandular stomach tumor-promoters; 4 were negative, including 3 liver carcinogens and a stomach irritant; and 2 were equivocal. Forty-five compounds were tested for ODC. Thirty-seven were positive, including 8 glandular stomach carcinogens and 6 glandular stomach tumor promoters; 7 were negative, including 3 liver carcinogens; and one was equivocal. All glandular stomach carcinogens and tumor-promoters examined were positive in both RDS and ODC. Two compounds were tested for c-fos and c-myc expression; one was a glandular stomach carcinogen and one was a glandular stomach tumor promoter, and both were positive. In addition, 2 compounds inhibited the increase in RDS induced by the tumor promoter NaCl, suggesting anti-tumor-promoter activity. Thus these assays are useful for assessing potential tumor-initiating and tumor-promoting activity in the rat glandular stomach.
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PMID:In vivo short-term assays for tumor initiation and promotion in the glandular stomach of Fischer rats. 787 43


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