Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antitumorigenic effect of cryptoporic acid E (CPA-E), a dimeric drimane sesquiterpenoid isolated from the fungus Cryptoporus volvatus, on colon carcinogenesis was investigated. Female F344 rats given an intrarectal instillation of 2 mg of N-methyl-N-nitrosourea 3 times weekly in weeks 1 and 2 were fed diet containing 0.2% CPA-E from week 3. Female ICR mice given 15 weekly intraperitoneal injections of 10 mg of 1,2-dimethylhydrazine/kg body weight during weeks 1 to 15 were fed diet containing 0.06% CPA-E from week 1. The experiment was terminated at week 35 for rats and at week 25 for mice. The incidence and the number of tumors per animal were reduced in CPA-E-fed animals compared to the controls: 31% vs. 75% (P less than 0.05) and 0.4 +/- 0.2 (SEM) vs. 0.9 +/- 0.2 (0.1 greater than P greater than 0.05) in rats, and 31% vs. 63% (0.1 greater than P greater than 0.05) and 0.4 +/- 0.2 vs. 2.4 +/- 0.8 (P less than 0.05) in mice (16 animals in each group). Intrarectal deoxycholic acid-induced colonic mucosal ornithine decarboxylase activity was significantly lowered in CPA-E-fed animals compared to controls. This shows an antipromoting activity of CPA-E against colon carcinogenesis. Thus, it was concluded that CPA-E inhibits colon cancer development in both rats and mice treated with 2 different colon carcinogens.
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PMID:Inhibitory effect of cryptoporic acid E, a product from fungus Cryptoporus volvatus, on colon carcinogenesis induced with N-methyl-N-nitrosourea in rats and with 1,2-dimethylhydrazine in mice. 139 20

In isolated nerve terminals from ox neurohypophyses the following concentrations of polyamines [pmol (microgram protein)-1 (mean +/- SEM)] were found: spermine: 2.07 +/- 0.14 (n = 3), spermidine: 0.22 +/- 0.01 (n = 4), putrescine: 0.20 +/- 0.01 (n = 4). In secretory granules isolated from the same tissue, the concentrations were: spermine: 0.57 +/- 0.02 (n = 3), spermidine: 0.07 +/- 0.04 (n = 3), putrescine: 0.13 +/- 0.04 (n = 3). After incubation of isolated nerve terminals with the polyamines, they were taken up as a function of time and concentration, approaching saturation at high concentrations. The kinetic parameters of their synthesizing enzyme, ornithine decarboxylase, in ox neurohypophyseal nerve terminals (apparent Km 0.75 mM and Vmax 22.5 pmol mg protein-1 h-1) were comparable to those previously found in cerebral cortex of rats. When isolated, hemilobes from rat neurohypophyses were incubated in a medium which contained spermidine (5 mM), and were stimulated by 56 mM K+, release of vasopressin was smaller than in control experiments. However, after removal of spermidine and after restimulation, 50 min after initial stimulation, the release was significantly elevated. It is suggested that polyamines may take part in modulation of vasopressin release.
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PMID:Polyamines in nerve terminals and secretory granules isolated from neurohypophyses. 144 36

Fasting and feeding have profound effects on crypt cell production and small bowel mucosal growth but the mechanism whereby food stimulates villus tip enterocytes to influence crypt cell production is unknown. We therefore measured the activities of ornithine decarboxylase (ODC), diamine oxidase (DAO) and alkaline phosphatase (ALP--a marker of enterocyte maturity) and polyamine concentrations in epithelial cells from villus tips, mid villi, lower villi and crypts of small intestine in non-fasted controls and 18-24 h fasted rats. Fasting reduced crypt cell production and caused villus hyperplasia, DAO activity (mU/g) increased in control villus tips from 9.6 +/- (SEM) 0.8 to 12.3 +/- 1.5 after fasting (NS), from 7.6 +/- 0.4 to 13.9 +/- 3.0 in mid villi (p less than 0.01), from 5.7 +/- 1.0 to 10.4 +/- 7.4 in lower villi (p less than 0.01) and from 5.4 +/- 0.9 to 12.8 +/- 1.5 in the crypts (p less than 0.001). ALP showed a similar pattern of results. In contrast, fasting lowered ODC activity (pmol/mg protein/h) dramatically from 319 +/- 82 in control villus tips to 16.7 +/- 3.0 during fasting, from 297 +/- 59 to 10.7 +/- 3.6 in mid villi, from 224 +/- 45 to 6.3 +/- 2.8 in lower villi and from 150 +/- 31 to 5.8 +/- 3.3 in the crypts. Fasting reduced putrescine concentrations in all fractions but particularly in the crypts and in general was associated with increases in spermidine and spermine concentrations. The role of DAO in the maintenance of low putrescine concentrations during fasting is unclear.
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PMID:Effect of fasting and feeding on polyamines and related enzymes along the villus: crypt axis. 212 64

The dramatic changes in morphology induced by nanomolar doses of tumor-promoting agents, especially in epithelial cells, have been noted previously (Driedger and Blumberg, 1980; Rifkin et al., 1979; Croop et al., 1980; Phaire-Washington et al., 1980; Ohuchi and Levine, 1980; Ojakian, 1981; Fey and Penman, 1984). This chapter shows the effect of the tumor promoter TPA on the underlying skeletal framework, which is involved in the maintenance of both cell and epithelial tissue morphology. It should be emphasized, however, that similar results are obtained for all the tumor promoters as well as for the complete, ultimate carcinogens examined so far. The organization of the cytoskeletal elements involved in these morphological changes is faithfully retained during the fractionation procedure employed here, as is evident from SEM and TEM analysis of Triton-extracted cells. A number of promoting agents have been compared, and the degree of disorganization viewed in these whole mounts appears to parallel the potency of the promoting agents as measured by other assays (Fey and Penman, 1984). Also, the inactive analogues of phorbol ester have no effect on cell structure (Rifkin et al., 1979; Ojakian, 1981; Fey and Penman, 1984). We suggest that the effect of TPA on the cytoskeleton occurs early as compared with many of the commonly studied biochemical responses and may indeed underlie many of the previously described cellular response to promoting agents, such as mitogenic stimulation. TPA-induced alterations in NM-IF scaffold occur in the absence of both protein and RNA synthesis (Fey and Penman, 1984). By contrast, plasminogen activator, stimulated by TPA (Wigler and Weinstein, 1976), is completely blocked by pretreatment with both cycloheximide and actinomycin D (Weinstein et al., 1977; Ojakian, 1981). Ornithine decarboxylase, another enzyme that is rapidly induced by tumor promoters, is inhibited by both cycloheximide and actinomycin D in the presence of TPA (O'Brien, 1976). Thus two of the early biochemical markers for tumor-promoter activity are separable from the induction of cytoskeletal alterations by TPA. One of the most striking features of the response to promoting agents is the adoption of the transformed phenotype, in which cells lose growth control and cease being organized into meaningful tissue structure. The alteration of desmosomal and junctional associations and the concomitant change in cytokeratin organization are clearly related to the breakdown of epithelial organization. The phenotype is completely reversible although it takes about 3 days for the mode line to reestablish normal morphology (data not shown).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The morphological oncogenic signature. Reorganization of epithelial cytoarchitecture and metabolic regulation by tumor promoters and by transformation. 307 72

The beneficial effects of alpha-difluoromethylornithine (DFMO) were assessed in a model of peripheral ischemia. DFMO is an irreversible inhibitor of ornithine decarboxylase (ODC), the initial enzyme in the production of polyamines. A 7 x 7 cm rat abdominal skin flap was surgically raised based on two inferior epigastric nerve, artery, and vein pedicles. One of the pedicles was then ligated and the skin was sutured back in place. Necrosis of skin was assessed 2 and 7 days after surgery. The rats were divided into four groups: control, DFMO, DFMO + polyamines, and polyamines alone. DFMO was administered in drinking water at 0.2%. Polyamines (putrescine, spermidine, and spermine) were each administered by daily i.p. injection at a dose of 10 mg/kg. The percentage of necrosis of the area of skin at risk in controls was 65 +/- 2% (mean +/- SEM). Necrosis was significantly reduced with DFMO (19 +/- 1%), with DFMO plus polyamines (37 +/- 3%), or with polyamines alone (41 +/- 2%). Protein synthesis and ornithine decarboxylase activity in the skin were both significantly decreased by DFMO. These studies demonstrate that DFMO protects skin from ischemic damage at least in part through actions on polyamine metabolism.
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PMID:Reduced cell death in skin flaps in rats treated with difluoromethylornithine. 311 14

Polyamine biosynthetic activity was assessed in various colorectal tissue samples consisting of noninvolved mucosa, benign adenomatous polyps and adenocarcinomas taken at surgery from a total of 40 patients. Ornithine decarboxylase (ODC) displayed a gradient of enzyme activity (i.e., adenocarcinoma greater than polyps greater than mucosa) which seemed to correlate positively with the neoplastic status of the tissue. In 10 of the patients, samples were obtained for all three tissue types. Five of these exhibited a clear repetition of the trends in enzyme activity seen with the mixed patient tissue sampling whereas the remainder differed by having the highest ODC activity in the polyps. In nine of the ten cases, ODC activity was substantially lower in the mucosa than in either of the neoplastic lesions. Trends in enzyme activity were the same for tissues obtained from either the colon or rectum. The ODC activity in adenocarcinomas could not be correlated with histologic differentiation, stage or site of the disease, however, in samples from female patients (all postmenopausal) the activity was elevated over normal mucosa to a greater extent (ten-fold) than in male patients (seven-fold). S-adenosylmethionine decarboxylase activity was assessed in 27 of the 40 patients and found to follow the same distribution as ODC; however, the mean value differences +/- SEM between tissues were less distinct. In general, tissue polyamine pool analysis of these same specimens reflected the levels of ornithine and S-adenosylmethionine decarboxylase activities. Overall, the data reveal an increase in polyamine biosynthetic activity in colorectal neoplasms, relative to surrounding mucosa, which may correlate with (1) progression of the neoplastic process, (2) the proportion of proliferating cells, (3) the rate of cell proliferation, or (4) a combination of two or all of these possibilities.
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PMID:Polyamine biosynthetic activity in normal and neoplastic human colorectal tissues. 362 Nov 11

Addition of 12-tetradecanoylphorbol 13-acetate (TPA) to cultures of intact Swiss mouse 3T3 fibroblasts induced a dose-dependent increase in ornithine decarboxylase (OrnDCase) activity. Over the same concentration range, 10(-9) to 10(-6) M, TPA induced the release of radioactively labeled fibronectin (FN) from the cells into the culture medium. Retinoic acid, a derivative of vitamin A, inhibited in a dose-dependent manner both the increase in OrnDCase activity and the release of FN induced by TPA. To examine the effects of TPA and retinoic acid in enucleated cells, the cells were treated with 7.5 micrograms of cytochalasin B per ml of medium during centrifugation at 10,000 X g for 35 min at 37 degrees C. In a series of five experiments, the treated cells were 94.7 +/- 4.8% (+/- SEM) enucleated as measured by [3H]thymidine incorporation and verified by Giesma staining for nuclei. In the enucleated cells, TPA did not induce increased OrnDCase activity but did induce FN release in a dose-dependent fashion over the same concentration range effective for FN release from intact cells. Moreover, addition of retinoic acid to the enucleated cells inhibited the phorbol ester-induced release of FN in a dose-dependent manner. A series of phorbol ester derivatives showed the same order of activity in causing FN release from the enucleated cells as reported for inducing OrnDcase activity in intact cells or in promoting mouse skin tumors in vivo. Similarly, several retinoids were tested for their ability to inhibit the phorbol ester-induced release of FN from enucleated cells. The efficacy of the retinoids in preventing FN release paralleled their activity in inhibiting phorbol ester-induced OrnDCase activity and skin tumor promotion, as reported in the literature. We conclude that at least one aspect of tumor promotion induced by phorbol esters--the loss of FN--does not require the cell nucleus, and further, that retinoids can inhibit this aspect of tumor promotion without nuclear involvement.
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PMID:Retinoids and phorbol esters alter release of fibronectin from enucleated cells. 695 35

Ornithine decarboxylase, a modulator of tissue growth during fetal and neonatal mammalian development, serves as a sensitive marker enzyme for perturbations in neural development. To test the hypothesis that cocaine is a central nervous system neurodevelopmental teratogen through mechanisms involving direct cellular injury, we measured ornithine decarboxylase activity in brain sections of 4- to 6-day-old rabbit pups which were prenatally cocaine exposed and in pair-fed and free-fed controls. Rabbit does were implanted with the osmotic minipump prior to Gestational Day 10 and cocaine and/or sterile water was delivered between Gestational Days 10 and 32. The flow rate in the cocaine group was calculated to provide a daily cocaine dose of 30 mg/kg/day. Pups were sacrificed, brains were dissected into the cortex, pons, and medulla, and ornithine decarboxylase activity was measured. When compared to the pair-fed group, prenatal cocaine exposure significantly decreased ornithine decarboxylase activity in the cortex (0.531 +/- 0.070 nmol/g/h SEM vs 0.913 +/- 0.201 nmol/g/h SEM; cocaine vs pair fed, respectively; P < or = 0.05) and in the pons (0.533 +/- 0.036 nmol/g/h SEM vs 0.728 +/- 0.075 nmol/g/h SEM, cocaine vs pair fed, respectively; P < or = 0.05) but not in the medulla (0.374 +/- 0.040 nmol/g/h SEM vs. 0.392 +/- 0.045 nmol/g/h SEM, cocaine vs pair fed, respectively; P > 0.05). Although there were no statistically significant differences in ornithine decarboxylase activity between the cocaine-exposed group and the free-fed group in any brain region, all regions showed a relative decrease in ornithine decarboxylase activity with prenatal cocaine exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prenatal cocaine exposure alters postnatal ornithine decarboxylase activity in rabbit brain. 812 93

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) 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


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