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)

We studied the effects of TSH on rat thyroid ornithine decarboxylase (ODC) activity. After 1 day of goitrogen treatment, there was an abrupt fall in serum triiodothyronine (T3) a rise in circulating TSH, and a dramatic increase in thyroid ODC activity. Despite the continued rise in TSH and progressive increase in thyroid gland size with further treatment, thyroid ODC activity declined on the third day and remained at submaximal levels. Thyroid ODC activity was also stimulated in a dose-related manner by administration of exogenous TSH. Little TSH effect was noted before 3 h. Maximal ODC activity occurred between 4 and 5 h. The TSH stimulation of ODC could be inhibited by pretreatment with actinomycin D or cycloheximide, suggesting that the increase in ODC activity requires new RNA and protein synthesis. Although pretreatment with agents that alter microtubule structure (e.g., colchicine and vinblastine) prevent stimulation of ODC activity by TSH, additional data suggest, but do not confirm, that hrmone secretion and ODC activation may be dissociable. Further studies were undertaken to determine whether cyclic AMP (cAMP) or prostaglandins played any role in the regulation of thyroidal ODC activity. Dibutyryl cAMP, alone, or together with aminophylline, did not stimulate thyroidal ODC activity in dosages which concomitantly stimulated adrenal enzyme activity. Likewise, prostaglandin E2 (PGE2) did not stimulate thyroidal ODC activity, but did stimulate adrenal enzyme activity in a dose-related manner. However, pre-treatment of rats with inhibitors of prostaglandin synthesis prevented the activation of thyroidal ODC BY TSH. One inhibitor, indomethacin, attenuated the TSH stimulation of enzyme activity in a dose-related manner. Indomethacin pretreatment also resulted in approximately a 10-fold decrease in thyroidal prostaglandin levels. Exogenous PGE9, in dosages as high as 500 pg, did not overcome the inhibitory effect of indomethacin on ODC activation. Although the precise role for endogenous prostaglandins remains to be defined, it does appear that a reduction in thyroidal prostaglandins prevents activation of the enzyme by TSH.
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PMID:Regulation of thyroid ornithine ornithine decarboxylase (ODC) by thyrotropin. I. The rat. 16 59

TSH (1.0 U im) caused a 22-fold increase in thyroidal ornithine decarboxylase activity (ODC) 6 hours after administration in intact rats. Hypophysectomized rats treated with 1 U TSH showed a 5-fold increase in thyroid ODC activity. This stimulation appeared to be specific for TSH since hormones known to induce ODC activity in other target tissues, such as ACTH or LH, showed no significant stimulation. DIBUTYRYL CYCLIC AMP and aminopylline caused a 12-fold increase in ODC activity 5 hours after administration. Prostaglandins have also been implicated in the TSH-induced stimulation of cyclic AMP. Indomethacin (1.0 mg/100 g body wt, ip), an inhibitor of prostaglandin synthesis, was administered 3 hours before TSH with a resulting 30% diminution (P less than .001) in ODC activity compared with the administration of TSH alone. To rule out the possibility that the increase in ODC activity with TSH might be due to increased thyroid hormone secretion, ODC activity was evaluated 6 hours after triiodothyronine administration (60 mug/100 g body wt), and no significant increase in thyroid ODC activity was found. Stimulation of ODC activity was 90% inhibited by the intraperitoneal administration of actinomycin D (80 mug/100 g body wt) or cycloheximide (400 mug/100 g body wt) given simultaneously with TSH. These results indicated that TSH specifically stimulated thyroid ODC activity, which may be important for the growth-promoting action of the hormone on the thyroid gland. This action may be mediated by cAMP and prostaglandins and may require new protein synthesis.
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PMID:Thyroid-stimulating hormone regulation of ornithine decarboxylase activity in the thyroid. 17 Nov 42

12-O-Tetradecanoylphorbol 13-acetate (TPA), an activator of protein kinase C (PKC), induced ornithine decarboxylase (ODC) in primary cultured mouse epidermal cells. Staurosporine, a potent protein kinase C inhibitor, also induced ODC activity. Both TPA- and staurosporine-caused ODC inductions were markedly suppressed in the PKC-down-regulated cells. Another PKC inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7), inhibited both TPA- and staurosporine-caused ODC inductions. H-7 by itself never induced ODC activity. Under our experimental conditions, staurosporine induced no detectable phosphorylation of endogenous proteins. TPA induced a translocation of PKC from cytosol to membrane whereas an optimal concentration of staurosporine to induce ODC did not induce an obvious translocation of PKC. Indomethacin, a cyclooxygenase inhibitor, inhibited staurosporine-caused ODC induction, but not TPA-caused ODC induction. Staurosporine induced specific morphological changes of epidermal cells both in normal and in PKC-down-regulated cells. These results indicate that staurosporine induces ODC activity in a PKC-dependent manner and morphological changes possibly through a PKC-independent mechanism. The mechanism of ODC induction caused by staurosporine may be in some way different from that caused by TPA.
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PMID:Protein kinase C-dependent and -independent actions of a potent protein kinase C inhibitor, staurosporine. 142 27

The mechanism of ornithine decarboxylase (ODC) induction by phorbol ester (TPA) has been studied in two permanent epithelial cell lines, a control (Ctr) and a Benzo (a) pyrene transformed line (BaP-tr); the degree of ODC gene expression (ODC-mRNA) was evaluated in comparison to the ODC activity. A small dose of TPA (4 x 10(-8) M) highly induced ODC activity in these cells. The induction levels differed however, corresponding respectively to 4:1 (induced: basal ODC) in Ctr cells and to 2:1 in BaP-tr cells. This difference reflected the variation of ODC gene expression; the ODC-mRNA induction was 6:1 in Ctr cells and 3:1 in BaP-tr cells. Repetitive TPA treatment decreased the ODC induction in these cells, as compared to that resulting from a single TPA treatment. Studies of ODC modulation were performed in presence of anti-inflammatory agents. In the two cell lines, Indomethacin (anti-cyclooxygenase) did not change the level of ODC induction by TPA. Nordihydroguaiaretic acid (NDGA, anti-lipoxygenase) inhibited this induced ODC. These results differed from that obtained in vivo in mouse skin. Dexamethasone (DXME, anti-phospholipase A2) showed different action according to treatment time. Used together with TPA (t0), DXME inhibited ODC induction by the carcinogen; with three hours delay after TPA (t3), DXME treatment stimulated ODC in the cells. This divergent action may be reproduced by Actinomycin D, while Cycloheximide only exhibited constant inhibition. Studies now in progress suggested that the inhibition of TPA induced ODC by DXME may reflect ODC gene repression, as for the stimulating effect it could be related to ODC post-transcriptional modulation, owing to the decrease of proteolytic action.
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PMID:[Specific induction by phorbol ester of the gene transcription and of the activity of ornithine decarboxylase in two control and transformed epithelial cell lines. Modulator effect of anti-inflammatory agents]. 152 Nov 67

The enzyme ornithine decarboxylase (ODC) has been shown to be induced by a number of conditions such as cold-injury, kindling, ischaemia and excitotoxin injection. In previous studies we have characterised the cortical response to kainate injection into the nucleus basalis and shown a substantial increase in both ODC mRNA and enzyme activity which reaches a maximum at 8h. This response is completely prevented by treatment with MK-801, indicating the involvement of NMDA receptors in mediating this response. Whilst NMDA receptors are known to gate a cation channel leading to increased calcium entry, an additional effect on the release of arachidonic acid has been reported. The possibility that NMDA receptor mediated activation of phospholipase A2 and release of arachidonic acid might mediate this ODC response was investigated in this study by treatment with the phospholipase inhibitors quinacrine and dexamethasone. Treatment of animals with quinacrine (100 mg/kg) at the time of injection of kainate into the nucleus basalis caused a significant attenuation of the induction of ODC in cerebral cortex of 43%. No further attenuation was seen at higher doses. A similar reduction in ODC induction was seen after treatment with dexamethasone (1 mg/kg) but a greater effect could be obtained (65% attenuation) at higher doses. The possible involvement of arachidonic acid derivatives in mediating ODC induction was further investigated by treatment with the cyclo-oxygenase inhibitor indomethacin and the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA). Indomethacin was able to significantly attenuate the induction of ODC (greater than 60%) whilst NDGA (30 mg/kg) was ineffective. These results indicate the possible role of arachidonic acid derivatives in the regulation of the expression of ODC in cerebral cortex after excitotoxin injection.
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PMID:Excitotoxin induction of ornithine decarboxylase in cerebral cortex is reduced by phospholipase A2 inhibition. 164 Aug 4

Our previous studies had suggested a link between bile salt stimulation of colonic epithelial proliferation and the release and oxygenation of arachidonate via the lipoxygenase pathway. In the present study, we examined the role of reactive oxygen versus end products of arachidonate metabolism via the cyclooxygenase and lipoxygenase pathways in bile salt stimulation of rat colonic epithelial proliferation. Intracolonic instillation of 5 mM deoxycholate increased mucosal ornithine decarboxylase activity and [3H]thymidine incorporation into DNA. Responses to deoxycholate were abolished by the superoxide dismutase mimetic CuII (3,5 diisopropylsalicylic acid)2 (CuDIPS), and by phenidone or esculetin, which inhibit both lipoxygenase and cyclooxygenase activities. By contrast, indomethacin potentiated the response. Phenidone and esculetin suppressed deoxycholate-induced increases in prostaglandin E2 (PGE2), leukotriene B4 (LTB4), and 5, 12, and 15-hydroxyeicosatetraenoic acid (HETE), whereas CuDIPS had no effect. Indomethacin suppressed only PGE2. Deoxycholate (0.5-5 mM) increased superoxide dismutase sensitive chemiluminescence 2-10-fold and stimulated superoxide production as measured by cytochrome c reduction in colonic mucosal scrapings or crypt epithelium. Bile salt-induced increases in chemiluminescence were abolished by CuDIPS, phenidone, and esculetin, but not by indomethacin. Intracolonic generation of reactive oxygen by xanthine-xanthine oxidase increased colonic mucosal ornithine decarboxylase activity and [3H]thymidine incorporation into DNA approximately twofold. These effects were abolished by superoxide dismutase. The findings support a key role for reactive oxygen, rather than more distal products of either the lipoxygenase or cyclooxygenase pathways, in the stimulation of colonic mucosal proliferation by bile salts.
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PMID:Role of reactive oxygen in bile salt stimulation of colonic epithelial proliferation. 300 68

NMRI and SENCAR, two stocks of mice commonly used in multistage skin carcinogenesis studies, were compared with respect to the effects of inhibitors of arachidonic acid metabolism for the following 12-O-tetra-decanoylphorbol-13-acetate (TPA)-elicited events: tumor promotion, DNA synthesis in vivo and in vitro, ornithine decarboxylase induction, and prostaglandin (PG) E2 synthesis. Previous work had shown that the cyclooxygenase inhibitor indomethacin enhanced TPA promotion in SENCAR mice. We report here that over the same dose range (50 to 200 micrograms) indomethacin caused a dose-dependent inhibition of promotion in NMRI mice. Significant reversal of this inhibition was achieved with concomitant application of 10 micrograms PGF2 alpha but not PGE2. DNA synthesis studies showed that low doses of indomethacin and flurbiprofen increased TPA-stimulated DNA synthesis in primary cultures from SENCAR mice; indomethacin suppressed this response in NMRI cultures. In vivo DNA synthesis studies showed the same pattern: indomethacin enhanced TPA-stimulated DNA synthesis in SENCAR mice but inhibited in NMRI mice. Other classes of inhibitors of arachidonate metabolism (i.e., the cyclooxygenase-lipoxygenase inhibitors 5,8,11,14-eicosatetraynoic acid and phenidone and the phospholipase A2 inhibitor dibromoacetophenone) had inhibitory activity in vitro and in vivo in both stocks of mice. Indomethacin was found to inhibit TPA-induced ornithine decarboxylase activity to the same extent in both mice. Indomethacin was also very effective in inhibiting TPA-induced PGE2 synthesis in both stocks of mice. 5,8,11,14-Eicosatetraynoic acid and phenidone were likewise suppressive in both stocks of mice. It is concluded that the NMRI and SENCAR mice respond similarly to TPA with respect to promotion, DNA synthesis, ornithine decarboxylase induction, and PG synthesis. The difference appears to be in the degree of involvement of the lipoxygenase pathway.
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PMID:Events associated with mouse skin tumor promotion with respect to arachidonic acid metabolism: a comparison between SENCAR and NMRI mice. 310 6

The mechanism of the anti-promoting effect of the prostaglandin (PG) synthesis inhibitor indomethacin in colon carcinogenesis was investigated. Male Sprague-Dawley rats received 0.002% water solution of indomethacin as drinking water freely for 3 days, then a subcutaneous injection of various doses of PGE2 and/or an intrarectal instillation of 12 mumol of sodium deoxycholate as a colon tumor promoter. Ornithine decarboxylase (ODC), a marker of tumor promotion, in the distal colonic mucosa was assayed at 4 hr after deoxycholate instillation. Indomethacin significantly suppressed the deoxycholate-augmented increase of ODC activity, while exogenous PGE2 restored or further increased the augmented ODC activity. The amount of PGE2 and the level of ODC activity were well correlated. However, PGE2 alone without deoxycholate did not increase the activity. Deoxycholate markedly increased colonic mucosal PGE2 at 1 hr after the instillation, and indomethacin decreased it. The results indicate that PGE2, the production of which is stimulated in the colonic mucosa by deoxycholate, is involved in the induction of colonic mucosal ODC. This is probably why PG synthesis inhibitors may inhibit the tumor promotion and prevent cancer development in the colon.
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PMID:Involvement of prostaglandin E2 in bile acid-caused promotion of colon carcinogenesis and anti-promotion by the cyclooxygenase inhibitor indomethacin. 311 24

The effects of lipoxygenase and cyclooxygenase inhibitors on ornithine decarboxylase (ODC) induction by a potent tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA) were examined in vitro in isolated mouse epidermal cells. Lipoxygenase inhibitors such as quercetin, nordihydroguaiaretic acid (NDGA), 3,4,2',4'-tetrahydroxychalcone, 3-amino-1-(3-trifluoromethylphenyl)-2-pyrazoline (BW755C) inhibited the TPA-caused ODC induction. Indomethacin, a selective cyclooxygenase inhibitor, failed to inhibit it. These results suggest that the lipoxygenase inhibitors inhibit TPA-caused epidermal ODC induction in mouse skin at least in part by acting directly on epidermal cells while cyclooxygenase inhibitor inhibits it indirectly by acting on cells other than epidermal cells, e.g. cells which are involved in the prostaglandin-dependent inflammatory process.
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PMID:The induction of ornithine decarboxylase caused by 12-O-tetradecanoylphorbol-13-acetate in isolated epidermal cells is inhibited by lipoxygenase inhibitors but not by cyclooxygenase inhibitors. 312 55

In androgenized-hypophysectomized rats, ovine prolactin stimulated the activity of the ornithine decarboxylase (ODC) of the lateral lobes, but not the ventral and dorsal lobes of the prostate glands in a time- and dose-dependent fashion. High degrees of enzyme stimulation were associated with significant elevations in the endogenous levels of its product, putrescine. The relative response to prolactin over basal activities was relatively unaffected by indomethacin but decreased with cycloheximide, suggesting that prostaglandins do not mediate the effects of the hormone, but that a high rate of protein synthesis is a prerequisite for its expression. Indomethacin alone significantly increased the basal activity of the enzyme above control levels, suggesting that prostaglandins may normally exert a degree of inhibition on the ODC. The selective activation of the lateral lobe ODC supports previous reports of a differential response of the various prostatic lobes to prolactin, and also provides a convenient biochemical response for examining details of prolactin action on this organ.
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PMID:Prolactin selectively stimulates ornithine decarboxylase in the lateral lobe of the rat prostate. 358 28


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