Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Various hormonal and non-hormonal agents were tested for their ability to induce ornithine decarboxylase (EC 4.1.1.17) in primary cultures of fetal rat liver cells that retain many of the differentiated functions of hepatocytes. The only agents to induce ornithine decarboxylase in this cell type were fetal calf serum, prostaglandin E1 and cyclic AMP derivatives. Also, the amino acid arginine would induce ornithine decarboxylase in this cell type following arginine starvation for 24 h. These observations are in contrast to the wide range of hormones, e.g. insulin, hydrocortisone, glucagon and growth hormone, than can induce ornithine decarboxylase in vivo in the adult rat liver but which are all without effect on fetal rat liver cells.
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PMID:Factors regulating the induction of ornithine decarboxylase in fetal rat liver cells in culture. 21 27

In rats fed ad libitum, a marked circadian rhythm with a peak at night was observed in the hepatic level of ornithine decarboxylase (ODC) [EC 4.1.1.17], the enzyme for the first step of polyamine synthesis. A similar rhythm was found in the hepatic content of putrescine, but not of spermidine or spermine. The mitotic activity of the liver also exhibited a clear rhythm with a peak in the daytime. The rhythms of both ODC and mitosis were generated by cyclic ingestion of proteinous food, since the peaks shifted when rats were meal-fed and both activities disappeared on starvation or protein deprivation. The close parallel between the rhythms suggested that synthesis of polyamine, especially that of putrescine, was a prerequisite for the rhythmic growth of liver. The dietary induction of hepatic ODC depended on the nutritive value of dietary protein; zein or gelatin was effective only when supplemented with limiting amino acids and there was a good correlation between the hepatic ODC level and the relative growth rate.
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PMID:Correlation between circadian rhythms of polyamine synthesis and cell proliferation in rat liver. 45 36

Addition of calf serum to serum-starved cultures of synchronized BHK cells induced temporary production of ornithine decarboxylase, irrespective of the phase of the cell cycle of the BHK cells. The induction depended on the duration of serum starvation and on the amount of serum added. In addition, incorporation of 3H-thymidine into the acid-insoluble fraction of BHK cells in the S phase was stimulated by this treatment.
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PMID:Induction of ornithine decarboxylase in synchronized BHK cells by calf serum after a short period of serum-starvation. 56 65

Ornithine decarboxylase (ODC), which initiates the biosynthesis of the polyamines putrescine, spermidine, and spermine, is encoded by the spe-1 gene of the fungus Neurospora crassa. This gene and its cDNA have been cloned and sequenced. The gene has a single 70-nucleotide intron in the coding sequence. The cDNA, comprising the entire coding region, recognizes a single 2.4-kb mRNA in Northern (RNA) blots. The mRNA transcript, defined by S1 mapping, has an extremely long, 535-base leader without strong secondary-structure features or an upstream reading frame. The translational start of the protein is ambiguous: a Met-Val-Met sequence precedes the Pro known to be the N terminus of the ODC polypeptide. The polypeptide encoded by the N. crassa spe-1 gene (484 amino acids) has 46% amino acid identity with that of Saccharomyces cerevisiae (466 amino acids) and 42% with that of mouse (461 amino acids). Alignment of the longer N. crassa sequence with S. cerevisiae and mouse sequences creates gaps in different sites in the S. cerevisiae and mouse sequences, suggesting that N. crassa ODC is closer to an ancestral form of the enzyme than that of either yeast or mouse ODC. N. crassa ODC, which turns over rapidly in vivo in the presence of polyamines, has two PEST sequences, found in most ODCs and other proteins with rapid turnover. In striking contrast to other eucaryotic organisms, the variation in the rate of ODC synthesis in response to polyamines in N. crassa is largely correlated with proportional changes in the abundance of ODC mRNA. Spermidine is the main effector of repression, while putrescine has a weaker effect. However, putrescine accumulation appears to increase the amount of active ODC that is made from a given amount of ODC mRNA, possibly by improving its translatability. Conversely, prolonged starvation for both putrescine and spermidine leads to the differentially impaired translation of ODC mRNA.
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PMID:Ornithine decarboxylase gene of Neurospora crassa: isolation, sequence, and polyamine-mediated regulation of its mRNA. 153 Aug 78

Ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase activity (SAMD) were measured in tumour tissue in mice during periods of starvation (24 h) and refeeding. Starvation led to a 60% reduction in tumour ODC activity. Refeeding normalised the activity within 4 h. Restitution in ODC activity, representing de novo enzyme synthesis, preceded DNA resynthesis. SAMD activity continued to fall along the increase in ODC activity during refeeding, while difluoro-methyl-ornithine (DFMO) caused a compensatory increase in SAMD activity as expected. A fall and regain in ODC activity was associated with inhibition and regrowth of the tumour. Starvation-refeeding was not related to any decrease in tumour polyamine concentrations, while systemic DFMO blockade was. Glucose stimulated ODC when refed orally, but not when given systemically. Tumour ODC activity was not decreased in refed mice by anti-insulin, a procedure that antagonised insulin's bioactivity. Exogenous insulin did not stimulate tumour ODC activity. Our results suggest that gastrointestinal metabolism of carbohydrates stimulates the release of a factor, which initiates both ODC activity and DNA synthesis in tumour cells. This factor was not insulin.
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PMID:Ornithine decarboxylase activity in mouse tumour tissue in response to refeeding and diet components. 183

Growth of rats fed with a synthetic diet was studied under control conditions (arginine-rich), arginine starvation, and arginine starvation/refeeding. Hepatic polyamine concentrations and ornithine decarboxylase (ODC-)activity were determined for each population. In the livers of arginine-starved rats putrescine was decreased to half the control content within 8 days; upon refeeding, it returned to control levels within another 8 days. Spermidine content in liver tissue of arginine-starved rats remained rather stable for 7 days, but thereafter dropped to half the original value within two days. Refeeding for a period of 11 days was not enough to restore the spermidine content. The effects of arginine starvation/refeeding on spermine were very similar to those of spermidine. ODC specific activity, when correlated with growth, was higher in livers of arginine-starved rats than in control animals. Refeeding caused a decrease in ODC-activity although growth arrest was completely released. This apparent uncoupling of growth and ODC stimulation supports the theory that ODC in rat liver is regulated at three levels: first the growth-related component which is observed after stimulation by growth-hormone; second the known feed back control by polyamines, e.g. via antizyme; third the regulation at the level of the substrate supply which has been shown in this work. This is not a unique finding since very similar results have been obtained in previous experiments with the protozoan Tetrahymena thermophila. A remarkable observation of these assays was that L-ornithine, when added to the arginine-free diet was not able to substitute for L-arginine in directing growth and growth related processes.
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PMID:Polyamine biosynthesis in arginine-starved and refed rats. 203 2

The total cellular mass of the small intestine is well controlled and can adapt, with hypo- or hyperplasia, to a wide variety of stimuli. Luminal nutrients, hormonal factors and pancreatic and biliary secretions have all been implicated in the regulation of intestinal mucosal growth. The polyamines (putrescine, spermidine and spermine) and the key enzyme controlling their synthesis (ornithine decarboxylase. ODC) are critical for many cell growth processes and appear to play important roles in intestinal growth. During intestinal adaptation in response to jejunectomy, lactation. pancreatic-biliary diversion, starvation-refeeding and feeding with kidney bean lectin, intestinal contents of ODC and polyamines are increased, paralleling increases in mucosal proliferative indices and DNA synthesis. With administration of the specific inhibitor of ODC (difluoromethylornithine, DFMO) the increase in ODC and polyamines is inhibited and intestinal growth is suppressed. In addition, the oral administration of exogenous polyamines results in precocious maturation of the neonatal rat intestine. These results suggest that the polyamines are important for intestinal growth.
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PMID:Polyamines in intestinal growth. 208 16

Control Chinese hamster ovary (CHO) cells and mutant CHO cells lacking ornithine decarboxylase activity (CHODC-) were used to study the regulation of polyamine uptake. It was found that the transport system responsible for this uptake was regulated by intracellular polyamine levels and that this regulation was responsible for the maintenance of physiological intracellular levels under extreme conditions such as polyamine deprivation or exposure to exogenous polyamines. Polyamine transport activity was enhanced by decreases in polyamine content produced either by inhibition of ornithine decarboxylase with alpha-difluoromethylornithine in CHO cells or via polyamine starvation of CHODC- cells. The provision of exogenous polyamines resulted in rapid and large increases in intracellular polyamine content followed by decreased polyamine transport activity. Soon after this decrease in uptake activity, intracellular polyamine levels then fell to near control values. Cells grown in the presence of exogenous polyamines maintained intracellular polyamine levels at values similar to those of control cells. Protein synthesis was necessary for the increase in transport in response to polyamine depletion, but appeared to play no role in decreasing polyamine transport. Bis(ethyl) polyamine analogues mimicked polyamines in the regulation of polyamine transport but this process was relatively insensitive to regulation by methylglyoxal bis(guanylhydrazone), a spermidine analogue known to enter cells via this transport system and to accumulate to very high levels.
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PMID:Regulation of polyamine transport in Chinese hamster ovary cells. 211 35

Genes of higher eucaryotic cells are considered to show only a limited response to nutritional stress. Here we show, however, that omission of a single essential amino acid from the medium caused a marked rise in the mRNA levels of c-myc, c-jun, junB and c-fos oncogenes and ornithine decarboxylase (ODC) in CHO cells. There was no general accumulation of mRNAs in amino acid-starved cells, since the gamma-actin, beta-tubulin, protein kinase C, RNA polymerase II, and glyceraldehyde-3-phosphate dehydrogenase mRNAs and the total poly(A)+ mRNA were not increased. The levels of c-myc, ODC, and c-jun mRNAs were elevated more by amino acid starvation than by inhibition of protein synthesis with cycloheximide, which is known to increase the levels of these mRNAs. Importantly, however, cycloheximide present during amino acid starvation reduced the rise in the levels of the mRNAs down to the level obtained with cycloheximide alone. This implies that protein synthesis is required for the accumulation of c-myc, ODC, and c-jun mRNAs in amino acid-deprived cells. The junB and c-fos mRNAs, instead, were increased to the same extent or less by amino acid starvation than by cycloheximide treatment. The accumulation of the c-myc mRNA in amino acid-starved cells was due to both stabilization of the mRNA and increase of its transcription. The rise in the c-jun mRNA level seemed to be caused merely by stabilization of the mRNA. Further, despite the inhibition of general protein synthesis, amino acid starvation led to an increase in the synthesis of c-myc polypeptide. The results suggest that mammalian cells have a specific mechanism for registering shortages of amino acids in order to make adjustments compatible with cellular growth.
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PMID:Deprivation of a single amino acid induces protein synthesis-dependent increases in c-jun, c-myc, and ornithine decarboxylase mRNAs in Chinese hamster ovary cells. 212 33

Starvation and difluoromethylornithine (DFMO) administration have profound affects on intestinal proliferation, ornithine decarboxylase activity, and tissue polyamine levels. Diamine oxidase activity may play a role in the regulation of proliferation, and the activity of this enzyme may be influenced by ornithine decarboxylase activity. To determine if diamine oxidase is influenced by starvation and DFM administration, ileal diamine oxidase activities were determined on mucosal homogenates from five groups of rats: fed control, starved for 48 h, fed group receiving DFMO, a starved/refed group, and a starved/refed group receiving DMFO. The homogenates from starved rats were found to have decreased ornithine decarboxylase activity and increased diamine oxidase activity when compared to control values. The homogenates from the DFMO group also were found to have decreased ODC activity however, mucosal diamine oxidase activity was also decreased. Refeeding produced a dramatic increase in ornithine decarboxylase activity and a minimal change in diamine oxidase activity. The preservation of diamine oxidase activity during starvation implies a need for the enzyme not related to mucosal proliferation or digestion. However, in the fed state, diamine oxidase activity may be more dependent on ornithine decarboxylase activity or its reaction product putrescine.
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PMID:Effects of starvation and difluoromethylornithine (DFMO) on diamine oxidase activity in rat ileum. 212 61


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