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)

Ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) purified from rat liver was affinity-labeled by alpha-[5-14C]difluoromethylornithine. On analysis by SDS-polyacrylamide gel electrophoresis, the radioactivity migrated as a single major peak that coincided with a single protein band of Mr 50,000. Calculation from bound radioactivity indicated that ornithine decarboxylase has two active sites, one for each subunit, and that pure enzyme should have a specific activity of about 1.4 x 10(6) nmol CO2/h per mg protein.
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PMID:Affinity labeling of purified ornithine decarboxylase by alpha-difluoromethylornithine. 681 35

Ornithine decarboxylase (ODC) activity and polyamine (putrescine, spermidine, spermine) concentrations were measured in parallel in enterocyte-like Caco-2 cells maintained under various culture conditions. ODC activity was maximal at the beginning of the exponential growth phase, decreasing dramatically thereafter to a negligible level at confluency (day 9). Kinetic studies performed on day 3 revealed the presence of a single enzyme with a Km around 200 microM and a Vmax of about 2 nmol CO2 released/h/mg protein. Similar values were obtained in both serum-supplemented and transferrin/selenium (TS)-defined culture media, indicating that ODC kinetic parameters are not affected by any factors present in serum. Polyamine concentrations were maximal on day 5. By day 9, they returned to initial levels and remained at these fairly high values until day 21. Since we have previously shown (Jumarie and Malo, 1994, in Vitro Cell. Dev. Biol., 30A:753-760) that triiodothyronine (T3) stimulates differentiation but not proliferation of Caco-2 cells maintained in TS-defined medium, we investigated if it induces differentiation by a polyamine-dependent mechanism. Short- and long-term measurements revealed similar ODC activity and polyamine levels whether T3 was present or not in the culture medium. These results clearly demonstrate that polyamine synthesis is more likely to be associated with Caco-2 cell proliferation, and that the T3 effect on Caco-2 cell differentiation does not involve polyamine biosynthesis. Moreover, our data show that ODC activity is not solely regulated by intracellular polyamine concentration.
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PMID:Ornithine decarboxylase activity is associated with proliferation but not with T3-induced differentiation of Caco-2 cells. 759 44

Cells in mitosis were harvested from exponentially growing Chinese hamster ovary cells by the mitotic detachment technique. Immediately after harvesting, the mitotic cells were seeded in tissue culture flasks and incubated at 37 degrees C in a CO2 incubator. Care was taken not to perturb the progression of cells through the cell cycle. At every hour after seeding for 14 h, cells were collected for analysis of cell cycle distribution, cellular polyamine content, ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC) activities, and relative mRNA contents. The progression through the cell cycle was monitored by DNA flow cytometry. The putrescine, spermidine, and spermine levels were approximately doubled during the cell cycle: putrescine mainly during late S and G2, spermidine continuously during the entire cell cycle, and spermine mainly during G1 and S. The ODC activity was low in seeded mitotic cells and the enzyme was activated in late G1 and reached a plateau in S phase. A second burst in activity was observed during late S phase and maximal ODC activity was found at the S/G2 transition. The relative ODC mRNA level approximately doubled during the cell cycle and the increase in the relative level mainly took part during mid and late S phase. AdoMetDC activity increased in late G1 and a first maximum was observed during the G1/S transition. A second burst in activity was found in mid S phase. Maximal AdoMetDC activity was found in G2. The relative AdoMetDC mRNA approximately doubled during the cell cycle and the increase in the relative level mainly took place during late G1 and early S phase. Our results indicate that polyamine synthesis was regulated at transcriptional and translational/post-translational levels during the cell cycle of Chinese hamster ovary cells.
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PMID:Ornithine decarboxylase and S-adenosylmethionine decarboxylase expression during the cell cycle of Chinese hamster ovary cells. 781 36

To investigate ornithine decarboxylase (ODC) activity and proliferating cell nuclear antigen (PCNA) in gastric cancer, ODC activity and PCNA were measured in 50 resected samples. The relationship between both and clinicopathologic factors was examined. ODC activity was 473.3 +/- 54.7 pmol CO2/60 min/mg protein in tumors, and 273.5 +/- 38.3 pmol CO2/60 min/mg protein in normal mucosa. ODC activity in tumors was significantly higher than that of normal mucosa. ODC activity in tumors was significantly high in gross type 4, maximum diameter more than 10 cm, depth se, infiltrative growth (INF) gamma, positive lymph vessel invasion and positive lymph node metastasis. PCNA-LI was 24.7 +/- 1.5% in tumors, and 13.9 +/- 1.1% in normal mucosa. PCNA-LI of tumors was significantly higher than that of normal mucosa. PCNA-LI of tumors was significantly high in gross type 2, histological type tub 2 and por, depth ss beta and se, IFN beta, positive lymph vessel invasion, positive venous invasion, and positive lymph node metastasis. ODC activity and PCNA-LI were closely related in normal mucosa, showing a correlation coefficient of 0.730. On the other hand, their relationship was weak in tumors, showing a correlation coefficient of 0.417. These results suggest the differentiation of value between ODC activity and PCNA-LI in gastric cancer. In gastric cancer, ODC activity and PCNA-LI in tumors may be good markers of lymph node metastasis. Furthermore, PCNA-LI may be a good marker of hematogenous metastasis.
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PMID:[A ornithine decarboxylase activity and proliferating cell nuclear antigen in gastric cancer]. 782 96

O6-Alkylguanine-DNA alkyltransferase (AGT) activity is associated with resistance of brain tumor cell lines to the cytotoxic effects of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). SF-763 cells exhibit high AGT activity and are resistant to BCNU. In this study, we compared the effects of the AGT inhibitor O6-benzylguanine (BG) on the cytotoxicity of BCNU in oxic and hypoxic SF-763 cells; we also measured AGT activity, ornithine decarboxylase (ODC) activity, and polyamine levels to determine if there was any correlation with cell survival as determined by colony-forming efficiency assay. Exponentially growing monolayer cells were pretreated with 10 microM BG for 2 h under oxic or hypoxic (95% nitrogen/5% CO2) conditions and then exposed to graded concentrations of BCNU for 1 h. BG significantly lowered AGT activity but had no cytotoxic effect in oxic or hypoxic cells; hypoxia alone was not cytotoxic. The cytotoxicity of BCNU was 4 times higher in BG-treated hypoxic cells than in oxic cells treated with BCNU alone; the BCNU doses required for a 1-log cell kill were 75 and 300 microM, respectively. ODC activity was lowered by hypoxia alone but was not significantly affected by BG in either hypoxic or oxic cells. Polyamine levels were not significantly affected by hypoxia or BG. These results indicate that pretreatment with BG dramatically lowers AGT activity and increases the cytotoxicity of BCNU in both oxic and hypoxic SF-763 cells. The mechanism of this enhanced cytotoxicity is apparently unrelated to ODC activity or polyamine levels.
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PMID:The effects of O6-benzylguanine and hypoxia on the cytotoxicity of 1,3-bis(2-chloroethyl)-1-nitrosourea in nitrosourea-resistant SF-763 cells. 825 97

Cyclosporine (CsA) is an inhibitor of ornithine decarboxylase (ODC), a key enzymatic step in cell proliferation. The purpose of this study was to determine the effect of CsA on islet cell mass. Partial obstruction (PDO) of the hamster pancreas is an established model of islet cell differentiation and proliferation in which regeneration is mediated by the induction of trophic activity (TA) that can be extracted from the pancreas. In Part 1 of these studies, hamsters were randomized to (i) Control (n = 5); (ii) PDO alone (n = 5); (iii) PDO + CsA (20 mg/kg ip daily) (n = 5); (iv) CsA alone (n = 5). On Day 21, 1 hr prior to sacrifice, animals received tritiated thymidine, 2 microCi/g body wt ip. Pancreata were excised for analysis of islet cell mass (No. islets/mm2) by morphometry and of cell proliferation (islet cell labeling index) by autoradiography. In Part 2 of these studies, hamsters were randomized to receive CsA (n = 34), as in Part 1, or saline (n = 30). After 7 days, animals received 1 ml of TA ip and were sacrificed after 0, 6, 8, and 10 hr. The pancreata were excised and determinations made of organ weight, DNA content, and ODC bioactivity (pmole/CO2/hr/mg DNA). Data (mean +/- SEM) were analyzed by ANOVA. In Part 1, the number of islets/mm2 in the PDO group was increased two-fold compared to control animals, those receiving CsA, and those undergoing PDO with CsA (2.4 +/- 0.1 vs 1.1 +/- 0.0, 1.4 +/- 0.2, 1.2 +/- 0.1, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cyclosporine and islet mass--implications for islet transplantation. 833 32

Ornithine decarboxylase (ODC), the lead enzyme in polyamine biosynthesis, was partially purified from Trichomonas vaginalis and its kinetic properties were studied. The enzyme appears to be of special significance in this anaerobic parasite, since the arginine dihydrolase pathway generates ATP as well as putrescine from arginine. ODC from T. vaginalis had a broad substrate specificity, decarboxylating ornithine (100%), lysine (1.0%) and arginine (0.1%). The enzyme had a pH optimum of 6.5, a temperature optimum of 37 degrees C and was pyridoxal 5'-phosphate-dependent. Attempts to separate ornithine- from lysine-decarboxylating activity by thermal-stability and pH-optima curves were not successful. Although Km values for ornithine and lysine were 109 and 91 microM respectively, and the Vmax values for these substrates were 1282 and 13 nmol/min per mg of protein respectively, the most important intracellular substrate is ornithine, since intracellular ornithine levels are 3.5 times those of lysine and extracellular putrescine levels are 7.5 times those of cadaverine. Ornithine was also an effective inhibitor of lysine-decarboxylating activity (Ki 150 microM), whereas lysine was relatively ineffective as inhibitor of ornithine-decarboxylating activity (Ki 14.5 mM). Crude ODC activity was localized (86%) in the 43,000 g supernatant and 3303-fold purification was obtained by (NH4)2SO4 salting and DEAE-Sephacel, agarose-gel and hydroxyapatite chromatography steps. The enzyme bound difluoro[3H]methylornithine ([3H]DFMO) with a ratio of drug bound to activity of 2500 fmol/unit, where 1 unit corresponds to 1 nmol of CO2 released from ornithine/min. The enzyme had a native M(r) of 210000 (gel filtration), with a subunit M(r) of 55,000 (by SDS/PAGE), suggesting that the trichomonad enzyme is a tetramer. From the subunit M(r) and binding ratio of DFMO, there is about 137 ng of ODC per mg of T. vaginalis protein (0.013%). The significant amount of ODC protein present supports the view that putrescine synthesis in T. vaginalis plays an important role in the metabolism of the parasite.
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PMID:Trichomonas vaginalis: characterization of ornithine decarboxylase. 834 28

Ornithine decarboxylase (ODC) is the first and often rate-limiting enzyme in polyamine biosynthesis. ODC and polyamines (putrescine, spermidine, spermine, and cadaverine) have an essential role in cell proliferation. In this study, we investigated ODC activity and the polyamine levels of normal human colonocytes isolated from the upper and lower crypt regions. We found no significant differences in ODC activity between upper and lower crypt regions (mean +/- SEM: 105 +/- 60 and 103 +/- 52 pmol CO2/mg protein/hr, respectively). This result was further substantiated by ODC immunoreactive antibody staining technique. Levels of polyamines (putrescine, spermidine, spermine, and cadaverine) were similar in the upper and lower crypt regions (mean +/- SEM; upper/lower: 79 +/- 29/79 +/- 18; 189 +/- 116/ 137 +/- 38; 174 +/- 58/204 +/- 35; and 52 +/- 10/51 +/- 10 nmol/mg protein, respectively). Acetyl-polyamines (acetyl-putrescine, acetyl-spermidine, and acetyl-spermine) levels in human colonocytes showed no significant differences between upper and lower crypt regions (mean +/- SEM; U/L: 368 +/- 109/408 +/- 89, 63 +/- 22/51 +/- 12, and 39 +/- 12/41 +/- 14 nmol/mg protein, respectively). Our results suggest that in isolated normal human colonocytes, ODC activity and polyamine levels are similar in the upper and the lower crypt regions.
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PMID:ODC activity and polyamine levels in isolated human colonocytes. 836 61

In fetal as well as newborn rats, acute hypoxic exposure results in significantly elevated brain ornithine decarboxylase (ODC) activity, polyamine concentrations, and ODC mRNA. The interpretations of these in vivo hypoxic-induced changes, however, are complicated by maternal confounding effects. To test the hypothesis that acute hypoxia will also increase ODC activity in vitro, we developed a brain slice preparation which eliminates such maternal effects. Sections of whole cerebrum, approximately 300-500 microns thick, were made from 3- to 4-day old Sprague-Dawley rat pups. The slices were equilibrated for 1 h in artificial cerebrospinal fluid (ACSF) continuously bubbled with 95% O2/5% CO2, prior to induction of hypoxia. We induced hypoxia by changing the oxygen concentration to 40%, 30%, 21%, 15%, 10%, or 0% O2, all with 5% CO2 and balance N2. In the normoxic control brain slices, low but stable basal ODC activity persisted for up to 5 h post-sacrifice. Slices in ACSF treated with bovine serum albumin (BSA), or both BSA and fetal bovine serum (FBS), however, showed stable ODC activity values 2- to 3-fold higher than slices in ACSF alone, for up to 5 h. In response to acute hypoxia (i.e., 15, 21, and 30% O2), ODC activity was elevated 1.5- to 2-fold above control values between 1 and 2 h after initiation of hypoxia. Qualitative light and electron microscopic examination of the neonatal brain slices following 2 h hypoxic exposure suggested that the great majority of cells did not show severe hypoxic damage or necrosis. It was concluded that: (1) in neonatal rat brain slices in vitro, stable ODC activity values approximating the whole brain ODC activity seen at sacrifice, can be maintained for several hours; (2) the in vivo hypoxic-induced increase in ODC activity can be approximated in vitro; (3) the neonatal rat brain slice preparation may be an alternative to other methods for studying hypoxic-induced ODC enzyme kinetics, or other brain enzymes, without maternal confounding effects; and (4) ODC activity may be an indicator of active metabolism within the newborn brain slice both in normoxia and hypoxia.
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PMID:Ornithine decarboxylase activity in vitro in response to acute hypoxia: a novel use of newborn rat brain slices. 854 23

The DNA damaging and cell proliferative activity of 1-methyl-1-nitrosourea (MNU), a glandular stomach carcinogen, was studied in the pyloric mucosa of male F344 rats after administration by gastric tube. DNA damage was measured with unscheduled DNA synthesis (UDS) and DNA single strand scission as markers, while cell proliferation was measured with replicative DNA synthesis (RDS) and ornithine decarboxylase (ODC) as markers. MNU at doses of 30 and 60 mg/kg body wt and 80 min after administration dose-dependently induced UDS (49 and 79 (0 dose, 19) dpm/micrograms DNA) measured by liquid scintillation counting in the presence of hydroxyurea (an inhibitor of RDS). RDS (DNA synthesis in the absence of hydroxyurea; 239 dpm/micrograms DNA at 0 dose) did not increase at that time. MNU at doses of 10 and 60 mg/kg body wt and 2 h after administration dose-dependently induced DNA single strand scission of 8.2 and 43.5 (0 dose, 1.4) elution rate constant (x 10(-3)/ml). MNU at doses of 30 and 60 mg/kg body wt and 24 h after administration dose-dependently induced an increase in RDS (1362 and 2393 (0 dose, 682) dpm/micrograms DNA). MNU at doses of 60, 90 and 120 mg/kg body wt and 24 h after administration dose-dependently induced an increase in ODC activity (22.0, 29.4 and 38.4 (0 dose, 6.3) p mol CO2/30 min/mg protein). These results suggest that MNU has possible tumor initiating activity (UDS and DNA single stand scission) and tumor promoting activity (RDS and ODC) in rat stomach mucosa.
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PMID:DNA damaging and cell proliferative activity of 1-methyl-1-nitrosourea in rat glandular stomach mucosa. 854 69


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