Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A possible minor route of ornithine catabolism in Aspergillus nidulans might begin with the ornithine decarboxylase reaction and end with the succinic semialdehyde dehydrogenase reaction. It is therefore of interest that the putative structural genes for these two enzymes, puA and ssuA, respectively, are tightly linked group II. However, this linkage is unlikely to have regulatory significance because ileA, the structural gene for threonine dehydratase, separates them. The gene order in this region is ssuA-ileA-puA-mauB-anB. (mauB- mutations result in loss of monoamine oxidase whilst anB- mutations lead to aneurin auxotrophy.) 2. An auxotrophy for ornithine or putrescine in A. nidulans occurs in double mutants lacking arginase and blocked before ornithine in the arginine biosynthetic pathway. Some residual ornithine synthesis in such double mutants can be catalysed by ornithine delta-transaminase, especially if it is synthesised constitutively.
Mol Gen Genet 1977 Feb 28
PMID:Some genetical aspects of ornithine metabolism in Aspergillus nidulans. 32 61

Genistein, an inhibitor of tyrosine kinase, was used to determine the possible role of tyrosine kinase in the prolactin (PRL) stimulation of milk product formation and ornithine decarboxylase (ODC) activation in cultured mouse mammary gland tissue. Genistein (10-200 microM) inhibited in a dose-response fashion the PRL stimulation of casein, lipid and lactose synthesis as well as ODC activation. Genistein, however, did not inhibit the phospholipase C, phorbol myristate acetate or cAMP effects on ODC activation. These results suggest the possible involvement of tyrosine kinase in the mechanism by which PRL expresses its effects in mammary gland tissues.
Mol Cell Endocrinol 1992 Jan
PMID:Effect of a tyrosine kinase inhibitor, genistein, on the actions of prolactin in cultured mouse mammary tissues. 131 59

Oligodeoxynucleotides 18 nucleotides in length having sequences complementary to regions spanning the initiation codon regions of ornithine decarboxylase or S-adenosylmethionine decarboxylase mRNAs were tested for their ability to inhibit translation of these mRNAs. In reticulocyte lysates, a strong and dose dependent reduction of ornithine decarboxylase synthesis in response to mRNA from D-R L1210 cells was brought about by 5'-AAAGCTGCTCATGGTTCT-3' which is complementary to the sequence from -6 to +12 of the mRNA sequence but there was no inhibition by 5'-TGCAGCTTCCATCACCGT-3'. Conversely, the latter oligodeoxynucleotide which is complementary to the sequence from -6 to +12 of the mRNA of S-adenosyl methionine decarboxylase was a strong inhibitor of the synthesis of this enzyme in response to rat prostate mRNA and the antisense sequence from ornithine decarboxylase had no effect. The translation of ornithine decarboxylase mRNA in a wheat germ system was inhibited by the antisense oligodeoxynucleotide at much lower concentration than those needed in the reticulocyte lysate suggesting that degradation of the hybrid by ribonuclease H may be an important factor in this inhibition. These results indicate that such oligonucleotides may be useful to regulate cellular polyamine levels and as probes to study control of mRNA translation.
Mol Cell Biochem 1992 Dec 16
PMID:Inhibition of ornithine decarboxylase and S-adenosylmethionine decarboxylase synthesis by antisense oligodeoxynucleotides. 133 19

A strain of Leishmania donovani has been described that is resistant to DL-alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase (OD-Case) activity, and contains 15-fold greater amounts of ODCase activity and protein than the wild type strain from which it was derived (Coons, T., Hanson, S., Bitonti, A.J., McCann, P.P., and Ullman, B. (1990) Mol. Biochem. Pharmacol. 39, 77-90). From this mutant strain, another ODCase overproducing L. donovani strain, DFMO16, was generated by virtue of its ability to proliferate under even higher concentrations of DFMO. To investigate the mechanism by which DFMO-resistant cells overexpress ODCase, the leishmanial ODCase gene was isolated by hybridization to a fragment of the L. donovani ODCase gene that was generated by the polymerase chain reaction. The nucleotide sequence of a 4.5-kilobase DNA fragment encompassed an open reading frame encoding 707 amino acids (Mr = 77,350). The leishmanial protein contained an extra approximately 200 amino acid NH2-terminal extension and lacked the COOH terminus of the mammalian ODCase. Northern blot analysis revealed two leishmanial OD-Case transcripts of 4.8 and 6.5 kilobases, both of which were amplified 10-20-fold in the DFMO16 cells. Genomic Southern blot analysis established that the augmented amount of ODCase activity and ODCase mRNA in the DFMO16 strain could be attributed to a approximately 10-20-fold amplification of the ODCase gene copy number. DFMO16 cells exhibited an unstable phenotype in that the amplification of the ODCase gene, the increased amount of ODCase transcript, the overproduction of ODCase activity, and the DFMO-resistance growth phenotype all reverted synchronously in the absence of selective pressure.
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PMID:Amplification and molecular cloning of the ornithine decarboxylase gene of Leishmania donovani. 133 39

Biosynthesis of the polyamines spermidine and spermine and their precursor putrescine is controlled by the activity of the two key enzymes ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC). In the adult brain, polyamine synthesis is activated by a variety of physiological and pathological stimuli, resulting most prominently in an increase in ODC activity and putrescine levels. The sharp rise in putrescine levels observed following severe cellular stress is most probably the result of an increase in ODC activity and decrease in SAMDC activity or an activation of the interconversion of spermidine into putrescine via the enzymes spermidine N-acetyltransferase and polyamine oxidase. Spermidine and spermine levels are usually less affected by stress and are reduced in severely injured areas. Changes of polyamine synthesis and metabolism are most pronounced in those pathological conditions that induce cell injury, such as severe metabolic stress, exposure to neurotoxins or seizure. Putrescine levels correlate closely with the density of cell necrosis. Because of the close relationship between the extent of post-stress changes in polyamine metabolism and density of cellular injury, it has been suggested that polyamines play a role in the manifestation of structural defects. Four different mechanisms of polyamine-dependent cell injury are plausible: (1) an overactivation of calcium fluxes and neurotransmitter release in areas with an overshoot in putrescine formation; (2) disturbances of the calcium homeostasis resulting from an impairment of the calcium buffering capacity of mitochondria in regions in which spermine levels are reduced; (3) an overactivation of the NMDA receptor complex caused by a release of polyamines into the extracellular space during ischemia or after ischemia and prolonged recirculation in the tissue surrounding severely damaged areas; (4) an overproduction of hydrogen peroxide resulting from an activation of the interconversion of spermidine into putrescine via the enzymes spermidine N-acetyltransferase and polyamine oxidase. Insofar as a sharp activation of polyamine synthesis is a common response to a variety of physiological and pathological stimuli, studying stress-induced changes in polyamine synthesis and metabolism may help to elucidate the molecular mechanisms involved in the development of cell injury induced by severe stress.
Mol Chem Neuropathol 1992 Jun
PMID:Polyamine metabolism in different pathological states of the brain. 135 85

Expression of the Trypanosoma brucei ornithine decarboxylase (ODC) gene in Escherichia coli behind the lambda phage PR promoter led to the production of a recombinant enzyme having the same subunit molecular weight as the native enzyme [4]. However, when the same gene is expressed behind the tac promoter or the phoA promoter, the ODCs produced by the transformed E. coli have subunit molecular weights approximately 2 kDa higher than that of the native enzyme. Amino terminal sequencing of the recombinant proteins indicates that the ODC synthesized under control of the lambda PR promoter actually starts at the second methionine (Met23) of the open reading frame, whereas those produced in the latter two cases begin at the first methionine (Met1). Analysis of the 5'-end of T. brucei ODC mRNA supports the conclusion that translation initiates at Met23. We postulate that, for the lambda PR promoter, translation initiates at Met23 instead of Met1 because of the formation of a stable secondary structure in the region of the Met1 and the presence of a good E. coli consensus translation initiation site upstream of Met23. We have constructed a new plasmid using the pho A promoter to express recombinant T. brucei ODC starting at Met23 in large quantities.
Mol Biochem Parasitol 1992 Oct
PMID:The translation initiation site of recombinant Trypanosoma brucei ornithine decarboxylase varies with different promoters. 143 79

We describe the first example of unstable gene amplification consisting of linear extrachromosomal DNAs in drug-resistant eukaryotic cells. alpha-Difluoromethylornithine (DFMO)-resistant Leishmania donovani with an amplified ornithine decarboxylase (ODC) gene copy number contained two new extrachromosomal DNAs, both present in 10 to 20 copies. One of these was a 140-kb linear DNA (ODC140-L) on which all of the amplified copies of the odc gene were located. The second was a 70-kb circular DNA (ODC70-C) containing an inverted repeat but lacking the odc gene. Both ODC140-L and ODC70-C were derived from a preexisting wild-type chromosome, probably by a conservative amplification mechanism. Both elements were unstable in the absence of DFMO, and their disappearance coincided with a decrease in ODC activity and an increase in DFMO growth sensitivity. These results suggest the possibility that ODC70-C may play a role in DFMO resistance. These data expand the diversity of known amplification mechanisms in eukaryotes to include the simultaneous unstable amplification of both linear and circular DNAs. Further characterization of these molecules will provide insights into the molecular mechanisms underlying gene amplification, including the ability of linear amplified DNAs to acquire telomeres and the determinants of chromosomal stability.
Mol Cell Biol 1992 Dec
PMID:Unstable amplification of two extrachromosomal elements in alpha-difluoromethylornithine-resistant Leishmania donovani. 144 81

Renal hypertrophy and hyperfiltration are early manifestations of human and experimental diabetes that may contribute to the late development of diabetic nephropathy. The biochemical events resulting in kidney growth in the diabetic state are completely unknown. Since growth of various tissues is accompanied by increased formation of polyamines, we studied whether polyamines were involved in the growth of the kidney observed in diabetic rats. This was done by measuring the activity of the rate-limiting enzyme in the polyamine pathway (ornithine decarboxylase; ODC) in kidneys from control, diabetic and insulin-treated diabetic animals. The ODC activity in the kidney was increased in the diabetic animals with a maximal rise 24 h after diabetes induction (6-fold, P less than 0.01); the activity thereafter declined. However, on day 14 the activity was still significantly elevated (2.5-fold, P less than 0.05). In insulin-treated diabetic animals the kidney ODC activity was only increased 3-fold (P less than 0.05) after 24 h, and for the rest of the study period the activity was about 1.8-fold higher than in control rats. After 14 days the kidneys from diabetic rats were significantly larger than kidneys from both control and insulin-treated diabetic rats, 1066 +/- 43 mg vs. 904 +/- 16 mg and 959 +/- 36 mg, respectively (P less than 0.01). For comparison, the ODC activity was also investigated in muscle. However, in muscle from diabetic animals the ODC activity declined steadily during the 14 days to 34% of control values (P less than 0.01), and insulin treatment completely normalized the ODC activity in muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1992 Jul
PMID:Increased ornithine decarboxylase activity in kidneys undergoing hypertrophy in experimental diabetes. 151 80

Two transfected cell lines, one carrying a mammalian ornithine decarboxylase (ODC) that is suppressed by polyamines and one carrying a trypanosomal ODC that is not, were used to ask whether ODC suppression is necessary for the antiproliferative activities of two polyamine analogs, N1,N8-bis(ethyl)spermidine (BES) and N1,N14-bis(ethyl)homospermine (BE444). Both analogs accumulated within cells and suppressed S-adenosylmethionine decarboxylase, as well as polyamine-sensitive mouse ODC activity. Neither drug was able to suppress the activity of the polyamine-refractory trypanosome ODC. But, whereas BE444 was able to inhibit growth of both cell lines, BES could inhibit only growth of cells carrying the polyamine-sensitive ODC, under conditions that cause prolonged depletion of endogenous polyamines. We conclude from these studies that the antiproliferative activity of BES, a less potent drug, requires the suppression of ODC. The efficacy of BE444 is enhanced by its ability to suppress ODC. However, it can function without ODC suppression, whereas BES cannot.
Mol Pharmacol 1992 Aug
PMID:Role of ornithine decarboxylase suppression and polyamine depletion in the antiproliferative activity of polyamine analogs. 151 27

Hypoxia causes remodeling of the pulmonary circulation that is dependent on increases in lungs polyamine contents. Mechanisms by which polyamines are regulated in hypoxic lung cells are unknown, but ornithine decarboxylase (ODC) activity, the initial enzyme in de novo biosynthesis, is depressed and polyamine transport is augmented in lungs from hypoxic rats (R.-T. Shiao et al. 1990. Am. J. Physiol. 259:L351-L358). To determine if hypoxia directly influences polyamine regulatory mechanisms in pulmonary vascular cells, we examined [14C]spermidine (SPD) transport and ODC activity in bovine main pulmonary artery smooth muscle cells (PASMCs) cultured under standard (culture medium Po2: greater than 100 mm Hg), "normoxic" (culture medium Po2: 50 to 70 mm Hg), or "hypoxic" (culture medium Po2: 18 to 30 mm Hg) conditions. Uptake of [14C]SPD in cells cultured under standard conditions was temperature- and concentration-dependent, exhibited saturation kinetics, and was abolished by metabolic inhibition. Modeling of transport according to Michaelis-Menten kinetics revealed that [14C]SPD uptake in cells cultured under standard conditions was characterized by Km and Vmax values of 0.78 microM and 4.5 pmol/min/10(6) cells, respectively. In comparison to cells cultured under standard conditions, Km was unaffected by culture under normoxic or hypoxic conditions while Vmax was increased to 18 pmol/min/10(6) cells in normoxic cells and to 33 pmol/min/10(6) cells in preparations cultured under hypoxic conditions. Inhibition of ODC with alpha-difluoromethylornithine (DFMO) also induced SPD transport, as evidenced by an increase in the Vmax to 65 pmol/min/10(6) cells. Both hypoxia- and DFMO-induced increases in [14C]SPD transport were suppressed by cycloheximide and actinomycin D, thus highlighting the importance of protein and RNA synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1992 Sep
PMID:Polyamine transport and ornithine decarboxylase activity in hypoxic pulmonary artery smooth muscle cells. 152 Apr 91


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