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

---

Query: EC:4.1.1.17 (ornithine decarboxylase)
6,351 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sertoli cells derived from 21-day-old rats were cultured in serum-free Ham's F-10 medium to allow a direct investigation of the effects of FSH on polyamine (PA) biosynthesis in a defined culture system. After 48 h in culture, the basal cellular content consisted predominantly of spermine (1.1 nmol/mg protein) with substantially lower amounts of spermidine (0.1 nmol/mg protein) and undetectable amounts of putrescine. Upon the addition of ovine FSH (3 X 10(-9) M), cellular spermine content became significantly elevated above the control value as early as 1 h after treatment, reaching a 2.5-fold stimulation by 4 h. Spermidine was also elevated by 4 h after FSH treatment, but remained less than 20% of the spermine concentration. At no time did the cellular content of putrescine increase to measurable levels. Extended time-course studies demonstrated that the FSH-induced cellular increase in spermine and spermidine content persisted up to 24 h during the continuous presence of FSH. Bu2cAMP (5 mM) invoked similar changes in PA levels when measured at 4, 8, and 24 h. Ornithine decarboxylase (ODC) activity, which catalyzes the production of putrescine, was increased by FSH in a temporal fashion similar to that of spermine production. Addition of alpha-difluoromethylornithine, an irreversible inhibitor of ODC, blocked increases in both ODC activity and PA in cells stimulated with FSH or Bu2cAMP. Pulse-chase experiments using [3H]ornithine demonstrate that putrescine is initially synthesized, and is subsequently converted to spermidine and spermine. These studies suggest that regulation of PA biosynthesis by FSH is largely expressed as increases in spermine, and to a lesser extent spermidine, suggesting that the more complex PAs may be involved in the regulation of Sertoli cell function.
...
PMID:Stimulation of polyamine biosynthesis by follicle-stimulating hormone in serum-free cultures of rat Sertoli cells. 302 35

The mechanism of spermidine-induced ornithine decarboxylase (ODC, E.C. 4.1.1.17) inactivation was investigated using Chinese hamster ovary (CHO) cells, maintained in serum-free medium, which display a stabilization of ODC owing to the lack of accumulation of putrescine and spermidine (Glass and Gerner: Biochem. J., 236:351-357, 1986; Sertich et al.: J. Cell Physiol., 127:114-120, 1986). Treatment of cells with 10 microM exogenous spermidine leads to rapid decay of ODC activity accompanied by a parallel decrease in enzyme protein. Analysis of the decay of [35S]methionine-labeled ODC and separation by two-dimensional electrophoresis revealed no detectable modification in ODC structure during enhanced degradation. Spermidine-mediated inactivation of ODC occurred in a temperature-dependent manner exhibiting pseudo-first-order kinetics over a temperature range of 22-37 degrees C. In cultures treated continuously, an initial lag was observed after treatment with spermidine, followed by a rapid decline in activity as an apparent critical concentration of intracellular spermidine was achieved. Treating cells at 22 degrees C for 3 hours with 10 microM spermidine, followed by removal of exogenous polyamine, and then shifting to varying temperatures, resulted in rates of ODC inactivation identical with that determined with a continuous treatment. Arrhenius analysis showed that polyamine mediated inactivation of ODC occurred with an activation energy of approximately 16 kcal/mol. Treatment of cells with lysosomotrophic agents (NH4Cl, chloroquine, antipain, leupeptin, chymostatin) had no effect on ODC degradation. ODC turnover was not dependent on ubiquitin-dependent proteolysis. Shift of ts85 cells, a temperature-sensitive mutant for ubiquitin conjugation, to 39 degrees C (nonpermissive for ubiquitin-dependent proteolysis) followed by addition of spermidine led to a rapid decline in ODC activity, with a rate similar to that seen at 32 degrees C (the permissive temperature). In contrast, spermidine-mediated ODC degradation was substantially decreased by inhibitors of protein synthesis (cycloheximide, emetine, and puromycin). These data support the hypothesis that spermidine regulates ODC degradation via a mechanism requiring new protein synthesis, and that this occurs via a non-lysosomal, ubiquitin-independent pathway.
...
PMID:Spermidine mediates degradation of ornithine decarboxylase by a non-lysosomal, ubiquitin-independent mechanism. 302 6

Ornithine decarboxylase (ODC) activity was elevated in the premalignant metaplastic columnar epithelium (mean activity, 0.13 unit/mg protein, N = 18 individual samples from 18 patients), compared to either adjacent gastric (mean activity, 0.02 unit/mg protein, N = 9) or small intestinal (mean activity, 0.02 unit/mg protein, N = 9) epithelium in patients with Barrett's esophagus. Enzyme activity ranged from 0 (less than detectable) to more than 0.5 unit/mg protein in the metaplastic tissue. However, neither putrescine, spermidine, spermine (as individual parameters), nor total polyamine contents were related to ODC activity in the individual patient biopsies. Spermidine/spermine ratios ranged from 0.38 to 2.18 and were also not related to enzyme activity in any apparent manner. Nevertheless, cell strains derived from the metaplastic tissue were growth inhibited by alpha-difluoromethylornithine, an enzyme-activated, suicide inhibitor of ODC. In two different cell strains derived from Barrett's epithelium, growth was affected with drug concentrations as low as 0.05 mM. While the mechanism responsible for the elevation in enzyme activity is unknown, the regulation of polyamine metabolism appears to be altered in this premalignant tissue. The growth inhibition of Barrett's epithelium-derived cell lines by ODC inhibitors suggests a potential role for these compounds in the treatment of this disease.
...
PMID:Ornithine decarboxylase and polyamine levels in columnar upper gastrointestinal mucosae in patients with Barrett's esophagus. 313 Jan 89

Partial hemitransection at the mesodiencephalic junction in the rat increased striatal and nigral putrescine concentrations on the lesioned side for at least 168 h, with maximal increases between 24 and 48 h. Spermidine and spermine levels declined at 24 h in the striatum, rising above control values at 48 h and further at 168 h. In the substantia nigra, they remained unchanged for the first 48 h and then increased by 168 h. Cadaverine in the striatum also increased at 48 h. On the intact side putrescine increased but to a much lesser extent (at 48 h in the striatum and at 24 and 48 h in the substantia nigra). Ornithine decarboxylase and diamine oxidase activities showed maximal increases at 24 h in the striatum of the lesioned side, whereas in the substantia nigra ornithine decarboxylase attained a very high value as early as 4 h after the operation and diamine oxidase activity peaked at 48 h. The enzyme activities returned toward the basal values at 168 h. On the intact side, ornithine decarboxylase showed a small increase starting at 4 h and diamine oxidase was enhanced at 48 h. These results indicate that the stimulation of biosynthetic and degradative enzymes of polyamine metabolism accompanied by marked and prolonged increases in putrescine may be essential events in the early phases of neuronal response to mechanical injury in the CNS.
...
PMID:Polyamines, ornithine decarboxylase, and diamine oxidase in the substantia nigra and striatum of the male rat after hemitransection. 313 33

Polyamines (putrescine, spermidine, and spermine) are normal cellular constituents able to modulate cellular proliferation and differentiation in a number of developing systems. Ornithine decarboxylase (ODC), the rate-limiting enzyme in the polyamine biosynthetic pathway, has been shown to be causally related to an increase in glycosaminoglycan synthesis in murine embryonic palatal mesenchyme cells (MEPM). In order to understand other mechanisms that exist to regulate polyamine levels in cells derived from the developing craniofacial area, the present study investigated the capacity of MEPM cells to accumulate exogenous putrescine and tests the hypothesis that polyamine transport can serve as an adaptational response of MEPM cells to a change in their ability to synthesize polyamines. Transport was initiated in confluent cultures of MEPM cells by the addition of 0.1 microCi/ml of 14C-putrescine. The rate of transport, monitored for 20-120 minutes, was found to be a time-dependent saturable process. The rate of initial transport, determined by incubating MEPM cells for 15 minutes in the presence of different concentrations (1.0-20.0 microM) of 14C-putrescine, was also found to be saturable, suggesting a carrier-mediated event. Lineweaver-Burk analysis of these data revealed an apparent Km of 5.78 microM and a Vmax of 2.63 nmol/mg protein/15 minutes. Transport measured either at 4 degrees C or in the presence of 2-4 DNP was dramatically inhibited. Thus, putrescine transport is an active process, dependent upon metabolic energy. Conditions in which 1) NaCl was iso-osmotically replaced with choline chloride or 2) the Na+-electrochemical gradient was dissipated with Na+, K+-specific ionophores resulted in a decreased rate of transport indicating that putrescine transport in these cells is Na+ dependent. Noncompetitive inhibition assays utilizing sulfhydryl reagents that blocked sulfhydryl groups inhibited putrescine transport, suggesting that sulfhydryl groups are important for putrescine uptake. Competitive inhibition assays demonstrated that while spermidine and spermine inhibited putrescine uptake, ornithine did not inhibit transport. Spermidine, spermine, and putrescine thus appear to share a common transport system that is separate from that for ornithine. Putrescine transport is subject to adaptive regulation in both exponentially growing and confluent cultures of MEPM cells.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Characterization of a polyamine transport system in murine embryonic palate mesenchymal cells. 313 32

A single topical application of chrysarobin (220 nmol) to SENCAR mouse skin produced alterations in epidermal polyamine levels distinctly different from that following a single topical treatment with 3.4 nmol of 12-O-tetradecanoylphorbol-13-acetate (TPA). Putrescine and spermidine levels were elevated prior to the induction of epidermal ornithine decarboxylase. In this regard, putrescine levels were elevated at 6 and 24 h after a single application of chrysarobin. In addition, putrescine levels were elevated with a second major peak at 64 h after chrysarobin which coincided with elevated epidermal ornithine decarboxylase activity. Spermidine levels were substantially elevated from 24 to 96 h (peak at 60 h) after a single treatment. TPA treatment produced peak elevations in epidermal putrescine levels at 6 h and epidermal spermidine levels at 24 h after a single treatment. Epidermal spermine levels were dramatically depressed following treatment with chrysarobin (peak depression of approximately 60% below control at 24 h), but only slightly altered following treatment with TPA. The time courses for changes in epidermal DNA synthesis in mouse skin following single treatments with 3.4 nmol of TPA or 220 nmol of chrysarobin also showed considerable differences. TPA treatment produced several waves of DNA synthesis at approximately 18 and 48 h after treatment, while chrysarobin produced a single broad peak at 72 h after treatment. Treatment with chrysarobin was also associated with an initial, dramatic inhibition in epidermal DNA synthesis (to 23% of the control value) which was much more extensive than that elicited by TPA. Inhibition of epidermal DNA synthesis following treatment with chrysarobin was observed within a few hours after treatment and remained depressed until approximately 36 h after treatment. Following treatment with both chrysarobin and TPA, higher levels of epidermal DNA synthesis correlated closely with higher molar ratios of spermidine/spermine, indicating a strong relationship between epidermal spermidine levels and epidermal cell proliferation induced by both promoters. The data suggest that TPA and chrysarobin bring about initial changes in epidermal polyamines by distinct mechanisms; however, both compounds ultimately lead to a dramatic stimulation of epidermal DNA synthesis. These data further support our working hypothesis that anthrones promote skin tumors by an initial mechanism different from that of the phorbol esters.
...
PMID:Alterations in epidermal polyamine levels and DNA synthesis following topical treatment with chrysarobin in SENCAR mice. 318 57

Chicks with genetically elevated renal arginase activity were fed crystalline amino acid diets varying in ornithine concentration (0, 1 or 2%) to assess the potential for precursor regulation of polyamine synthesis. Renal arginase and renal and hepatic ornithine decarboxylase activities fell when ornithine was fed. Renal and hepatic ornithine concentrations rose while putrescine concentrations varied quadratically with ornithine feeding. Spermidine and spermine concentrations were not affected by diet. It was concluded that ornithine synthesized in vivo was a more potent stimulator of polyamine synthesis than ornithine of dietary origin.
...
PMID:Effect of dietary ornithine on renal and hepatic polyamine synthesis. 325 84

The importance of changes in polyamine metabolism for myocardial growth was assessed by measuring the activity of ornithine decarboxylase (ODC) and the polyamines spermidine, spermine and putrescine in hearts from spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. The rats were 30-weeks-old and had received 6 weeks treatment with either minoxidil (0.08 mg/ml) or alpha-methyldopa (5 mg/ml in drinking water). Left ventricular ODC activity was greater in the untreated SHR than the WKY rats at 4, 16 and 20 weeks of age. Spermidine content was consistently raised and spermine content reduced in the untreated SHR left ventricles, resulting in the high spermidine/spermine ratios characteristic of rapidly growing systems. Minoxidil treatment increased left ventricular weight and spermidine (83 and 61% in WKY and SHR rats, respectively) and spermine (44 and 28%) content. Methyldopa also caused an increase in left ventricular spermidine content (30 and 57% in WKY and SHR rats, respectively) despite a marked reduction in ventricular mass. Thus the ventricular hypertrophy in SHR rats is accompanied by enhanced synthesis and accumulation of polyamines. The fact that myocardial spermidine content increased during methyldopa treatment, which reduced myocardial mass, suggests that the polyamines are not causally related to the development of ventricular hypertrophy.
...
PMID:Cardiac polyamine metabolism in spontaneously hypertensive rats: effect of antihypertensive treatment. 347 31

Ferulic acid (FA) specifically inhibits the growth of the ventral prostate in rats not through antiandrogenic mechanisms (Saito et al. Experientia 35: 696, 1979). Levels of polyamines in the rat ventral prostate were determined before and after FA administration (10, 25 and 50 mg/kg BW, s.c., for 5 days). SD strain male rats, 5 approximately 7 weeks of age, were used. The ventral prostates were homogenized with 10% TCA and centrifuged. The supernatant was washed twice with diethylether, freeze-dried, and redissolved in distilled water. Then, the contents of putrescine, spermidine and spermine were measured by an isotachograph (LKB), using a leading buffer composed of 5 mM Ba(OH)2/15 mM valine, pH 9.94, and a terminating buffer composed of 20 mM triethylenediamine, pH 10.20. Total polyamines were reduced dose-dependently (12.12, 9.95, 9.10 and 7.74 nmol/mg wet tissue at 0, 10, 25 and 50 mg/kg FA, respectively). Spermidine was more sensitive to FA than spermine. According to the attitude of the Spermidine/Spermine ratio, the inhibition of ornithine decarboxylase by FA has been suggested.
...
PMID:[Effect of trans-4-hydroxy-3-methoxycinnamic acid (ferulic acid) on polyamine level in the rat ventral prostate]. 360 66

We have recently isolated, without using any inhibitors, a mutant of Chinese hamster ovary cell line which greatly overproduces ornithine decarboxylase in serum-free culture. Addition of polyamines (putrescine, spermidine, or spermine, 10 microM) or ornithine (1 mM), the precursor of polyamines, to the culture medium of these cells caused a rapid and extensive decay of ornithine decarboxylase activity. At the same time the activity of S-adenosylmethionine decarboxylase showed a less pronounced decrease. Notably, the polyamine concentrations used were optimal for growth of the cells and caused no perturbation of general protein synthesis. Spermidine and spermine appeared to be the principal regulatory amines for both enzymes, but also putrescine, if accumulated at high levels in the cells, was capable of suppressing ornithine decarboxylase activity. The amount of ornithine decarboxylase protein (as measured by radioimmunoassay) declined somewhat more slowly than the enzyme activity, but no more than 10% of the loss of activity could be ascribed to post-translational modifications or inhibitor interaction. Some evidence for inactivation through ornithine decarboxylase-antizyme complex formation was obtained. Gel electrophoretic determinations of the [35S]methionine-labeled ornithine decarboxylase revealed a rapid reduction in the synthesis and acceleration in the degradation of the enzyme after polyamine additions. No decrease in the amounts of the two ornithine decarboxylase-mRNA species, hybridizable to a specific cDNA, was detected, suggesting that polyamines depressed ornithine decarboxylase synthesis by selectively inhibiting translation of the message.
...
PMID:Control of ornithine decarboxylase in Chinese hamster ovary cells by polyamines. Translational inhibition of synthesis and acceleration of degradation of the enzyme by putrescine, spermidine, and spermine. 372 8


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---