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)

The binding of 3,5,3'-L-triiodothyronine (T3) and thyroxine (T4) on liver nuclear receptors and the activity of malic enzyme and ornithine decarboxylase was examined in infantile rats aged in 1, 3, 7, 23, 29 days and in adult rats. No changes in the affinity constants (Ka) of nuclear receptors were observed for T3 or T4. The maximum binding capacity (MBC) estimated with the use of Scatchard plot analysis was unchanged for T3, the highest MBC for 125I-T4 being noted in rats aged 7 days. Malic enzyme activity in rat liver during the first three neonatal weeks was almost undetectable, but markedly increased on the 29th day. Ornithine decarboxylase activity was found to be significantly higher on the first day after birth as compared with that of the remaining age groups. The findings indicate that the thyroid hormone-nuclear receptor complex in rat liver does not seem to be sufficient for the induction of these enzymes in postnatal period of life.
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PMID:Nuclear binding of thyroid hormones and activity of malic enzyme and ornithine decarboxylase in rat liver during postnatal development. 209 77

Retinoids bearing azido photoaffinity-labeling groups (azidoretinoids) have potential as probes for investigating the molecular mechanisms of action of all-trans-retinoic acid (RA) as mediated by its cellular retinoic acid-binding protein (CRABP) and nuclear receptor proteins. Two new azidoretinoids, 3-azido-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1E- propen-1-yl]-benzonic acid and 4-(4-azido-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-anthracenyl)be nzoic acid were synthesized, and evaluated for their in vitro biological potency, and binding affinity for CRABP. Like RA, these aromatic azides had significant activity in modulating cell differentiation in retinoid-deficient hamster tracheal organ culture (ED500.02 nM and 0.03 nM, respectively) and in the inhibition of the induction of ornithine decarboxylase in mouse epidermis (ED50 7.0 nmol and 0.5 nmol, respectively). They also possessed high binding affinity for CRABP (ID50 0.9 microM and 0.85 microM, respectively). The tritiated aromatic azides were further evaluated for their ability to bind covalently to CRABP after photolysis. On photolysis at -78 degrees C, the two radiolabeled azidoretinoids formed stable adducts with CRABP. Treatment of the adducts with either RA or p-chloromercuriphenylsulfonic acid (CMPS) and subsequent dialysis did not cause any dissociation, indicating the formation of a covalent bond. In contrast, treatment of the unirradiated complexes with RA or CMPS led to dissociation of the complex. Synthesis of affinity labels and characterization of CRABP-retinoid complexes should provide useful information on the ligand-binding regions and insights into the mechanism of action of RA.
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PMID:Biologically active aromatic retinoids bearing azido photoaffinity-labeling groups and their binding to cellular retinoic acid-binding protein. 216 70

Fusarium sp. contaminated feedstuffs elicit adverse estrogenic effects in several commercially important animal species via the mycotoxin zearalenone. An estrogenically active synthetic derivative, zearalanol, is used as an anabolic agent in cattle. Since estrogens can irreversibly alter target tissue development, we investigated the estrogenic activity of these compounds in the neonatal rat uterus. Both induced dose-dependent premature uterine growth when injected daily on postnatal days 1-5 (ED50 = 1.3 mg/kg BW). Nuclear estrogen receptor levels dramatically increased 1 hour after either a single injection on day 5 or after five daily injections. In 5-day-old animals, the translocated nuclear receptor was characterized as a single class of binding sites with a dissociation constant (KD) for estradiol (E2) of 1 nM. At 15 days, zearalanol-treated animals showed greater uterine nuclear receptor retention than zearalenone-treated animals. In 5-day-old animals, single mycotoxin doses induced five fold elevations of ornithine decarboxylase (ODC) at 6 hours. Unlike the growth response, ODC dose-response studies showed zearalanol to be about 20-fold more effective than zearalenone. Time course studies revealed that a low dose of zearalenone, but not of zearalanol, resulted in a shift in peak activity from 6 to 8 hours. These data suggest that metabolism of zearalenone may be important in short-term pharmacodynamics. In a competitive binding assay, neither compound competed [3H]E2 from the E2 binding site on alpha-fetoprotein. We conclude that the uterine growth response and ODC induction demonstrate the neonatal estrogenic action of these mycotoxins, apparently mediated via the estrogen receptor. The greater effectiveness of zearalanol in inducing ODC may be related to nuclear retention and/or zearalenone metabolism.
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PMID:Estrogenic activity of zearalenone and zearalanol in the neonatal rat uterus. 623 18

Cholera toxin administered by intrauterine injection to ovariectomized rats increased uterine ornithine decarboxylase activity as much as systemic estradiol at 4 h after treatment. At 45-60 min after treatment, however, cholera toxin did not increase nuclear estrogen receptor or stimulate synthesis of the uterine "induced protein," which is closely correlated with nuclear receptor, whereas estradiol caused substantial increases in both nuclear receptor and induced protein synthesis. Intrauterine injection of cholera toxin also produced an estrogen-like elevation of the uterine protein/DNA ratio at 24 h. Because both cholera toxin and estradiol are known to increase vascular permeability, our results support the hypothesis that some uterine effects of estradiol are not mediated by receptor-genome interaction but involve another mechanism that is associated with increased vascular permeability.
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PMID:Estrogen-like stimulation of uterine ornithine decarboxylase by cholera toxin. 670 55

During studies to determine the mechanism of tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA), we found that TPA downregulates mouse epidermal retinoic acid nuclear receptors (RAR), a superfamily of nuclear steroid/thyroid receptors implicated in mediating effects of retinoic acid (RA). Application of TPA to mouse skin decreased the binding of [3H]RA to RAR from mouse epidermal nuclear extracts. In this experiment, 20 nmol of TPA was applied to mouse skin and 3.5 h later binding of [3H]RA to RAR was analyzed by chromatography on a size-exclusion column. TPA treatment resulted in an approximately 67% decrease in the specific binding of [3H]RA to RAR. In a more detailed time course, application of 20 nmol of TPA to mouse skin led to 20, 36, 92 and 0% decrease in the binding of [3H]RA to mouse epidermal RAR at 2, 4, 12 and 72 h after treatment respectively. Okadaic acid, an inhibitor of protein phosphatases 1 and 2A but a mouse skin tumor promoter, also inhibited the binding of RA to RAR. RAR alpha and RAR gamma, but not RAR beta mRNA, could be detected in mouse epidermis. In addition, RA nuclear receptor RXR alpha was also expressed in the mouse epidermis. As determined by Northern blot analysis of total as well as poly(A)+ RNA, application of 10 nmol of TPA to mouse skin led to decreased expression of RAR alpha, RAR gamma and RXR alpha mRNA at 3.5 h after treatment. The effect of TPA on the attenuation of RAR expression was specific. Specific binding of RA to RAR was decreased when TPA-induced expression of the c-fos, c-jun and ornithine decarboxylase gene was increased. Downregulation of RAR(s) may be an essential component of the mechanism of mouse skin tumor promotion.
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PMID:Retinoic acid nuclear receptors and tumor promotion: decreased expression of retinoic acid nuclear receptors by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate. 814 83

All epithelial cells require retinoic acid for growth, maintenance, and differentiation. Although the epithelial cells that line the gastrointestinal tract are exposed to extreme retinoid concentration fluctuations in luminal fluid, whether proliferation and differentiation in these cells are significantly affected is not known. We have investigated this question using Caco-2 cells as a model because, although they are derived from a colon adenocarcinoma, they differentiate spontaneously in a manner similar to enterocytes in the small intestine. We found that retinoic acid caused maximum inhibition of cell growth and ornithine decarboxylase activity during the proliferative period. Retinoic acid increased brush border enzyme activities only in differentiating cells but stimulated transglutaminase activity in cells at all stages. In untreated proliferating cells, we found an early peak of transglutaminase activity that has not been reported before. Retinoic acid in intestinal cells acts through its nuclear receptor, RAR beta. The nuclear distribution of this receptor has not been demonstrated. In this study, we show that RAR beta responds to increasing concentrations of retinoic acid with a shift to the nuclear membrane in undifferentiated cells and progressive aggregation, diffusion, and loss in differentiated cells. We conclude that retinoic acid can inhibit proliferation and stimulate differentiation in Caco-2 cells depending on concentration and cell stage, and that these effects are accompanied by changes in distribution, as well as by the loss of RAR beta.
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PMID:Altered distribution of the nuclear receptor RAR beta accompanies proliferation and differentiation changes caused by retinoic acid in Caco-2 cells. 883 19

1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) is known to be involved in regulating the proliferation of parathyroid cells and PTH synthesis through reactions involving its nuclear receptor. We evaluated the effects of 1,25-(OH)2D3 and its hexafluorinated analog, 26,26,26,27,27,27-hexafluoro-1,25-dihydroxyvitamin D3 (26,27-F6-1,25-(OH)2D3), on parathyroid cells. The 1,25-(OH)2D3 and 26,27-F6-1,25-(OH)2D3 each inhibited [3H]thymidine incorporation and ornithine decarboxylase (ODC) activity, which is important in cell proliferation, in primary cultured bovine parathyroid cells. The inhibitory effect of 26,27-F6-1,25-(OH)2D3 on PTH secretion from parathyroid cells was significantly more potent than that of 1,25-(OH)2D3 between 10(-11) M and 10(-8) M. Study of 26,27-F6-1,25-(OH)2D3 metabolism in parathyroid cells in vitro elucidated its slower degradation than that of 1,25-(OH)2D3. After 48 h of incubation with [1beta-3H]26,27-F6-1,25-(OH)2D3, two HPLC peaks, one for [1beta-3H]26,27-F6-1,25-(OH)2D3, and a second larger peak for [1beta-3H]26,27-F6-1,23(S),25-(OH)3D3, were detected. No metabolites were detected after the same period of incubation with 1,25-(OH)2[26,27-3H]D3. We observed that 26,27-F6-1,23(S),25-(OH)3D3 was as potent as 1,25-(OH)2D3 in inhibiting the proliferation of parathyroid cells. Data suggest that the greater biological activity of 26,27-F6-1,25-(OH)2D3 is explained by its slower metabolisms and by the retention of the biological potency of 26,27-F6-1,25-(OH)2D3 even after 23(S)-hydroxylation.
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PMID:Increased biological potency of hexafluorinated analogs of 1,25-dihydroxyvitamin D3 on bovine parathyroid cells. 1062 14