Disease relevance of ODC1

• In intact rat lungs, hypoxia depresses ornithine decarboxylase activity, the initial rate-limiting enzyme in de novo polyamine synthesis, and enhances uptake of PUT from the vascular compartment, thus suggesting that increased polyamine transport is the driving mechanism behind hypoxia-induced increases in lung polyamine contents [1].
• The native ODC of E. coli is activated by ATP, GTP, CTP and UTP at 10(-3) M concentration to around 170-300% [2].
• The role of Na+ and Na(+)-H+ exchange in the stimulation of ornithine decarboxylase (ODC) activity has been investigated in a human colon adenocarcinoma cell line, LoVo [3].

High impact information on ODC1

• The type 2 messages (ornithine decarboxylase, actin, and alpha-tubulin) were regulated posttranscriptionally through activation of protein kinase C [4].
• Addition of ornithine or alpha-difluoromethylornithine, a specific inhibitor of ornithine decarboxylase, has no effect on these cells [5].
• DFMO strongly inhibited DNA synthesis and proliferation of bovine pulmonary artery endothelial (BPAE) cells in culture and decreased their ornithine decarboxylase activity and intracellular polyamine concentrations [6].
• Tumor angiogenesis and polyamines: alpha-difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase, inhibits B16 melanoma-induced angiogenesis in ovo and the proliferation of vascular endothelial cells in vitro [6].
• alpha-Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, inhibited B16 melanoma-induced angiogenesis in chick embryo chorioallantoic membrane and subsequently the growth of the tumor on the chorioallantoic membrane [6].

Biological context of ODC1

• The clone (1758 base pairs) consisted of 5'- and 3'-untranslated regions of 185 and 187 nucleotides, respectively, and an open reading frame of 1383 nucleotides encoding an ODC protein (M(r) 51,342 daltons) of 461 amino acids [7].
• A cDNA coding for ornithine decarboxylase (ODC) was isolated from a bovine liver cDNA library [7].
• Estradiol-induced cell growth and ODC activity were observed only in the presence of 10% charcoal-treated fetal bovine serum, suggesting that serum factors are required for estrogen action. alpha-Difluoromethylornithine (DFMO, 0.1 mM), a specific inhibitor of ODC, blocked the estradiol-induced cell proliferation and ODC activity [8].
• When excess putrescine accumulation in the presence of methylglyoxal bis(guanylhydrazone) was inhibited with alpha-methylornithine, a competitive inhibitor of ornithine decarboxylase, the inhibition of DNA replication was accentuated, with still no effect on protein or RNA synthesis [9].
• These studies suggested that the accumulation of cAMP and the induction of ODC by PTH are good markers of the differentiated phenotype of cultured chondrocytes [10].

Anatomical context of ODC1

• Hormone-responsive cells exhibited differential sensitivity to DFMO; resistant cell lines (e.g., MCF-7) were found to possess higher endogeneous levels of ODC than sensitive cell lines (e.g., T-47D and ZR-75-1) [8].
• Mitogenic signaling pathways regulating expression of c-myc and ornithine decarboxylase genes in bovine T-lymphocytes [11].
• Effect of thyrotropin on ornithine decarboxylase and of polyamines on RNA polymerase in the thyroid [12].
• Keratinocyte ornithine decarboxylase activity was maximal at pH 6.3 in MES buffer in the presence of dithiothreitol and EDTA [13].
• Calcium stimulates ornithine decarboxylase activity in cultured mammalian epithelial cells [14].

Associations of ODC1 with chemical compounds

• In the presence of ethylglyoxal bis(guanylhydrazone) and the ornithine decarboxylase inhibitor alpha-difluoromethylornithine, the cellular contents of putrescine, spermidine, and spermine were decreased by 75 to 90, 65 to 80, and 40 to 60%, respectively, compared with control cultures [15].
• Despite identical polyamine levels, the degree of inhibition of DNA and protein synthesis by EGBG was smaller than that observed with MGBG, in either the presence or absence of the ornithine decarboxylase inhibitor, alpha-difluoromethylornithine [16].
• This estradiol-induced proliferation was associated with a peak (at 12-24 h) of activity of ornithine decarboxylase (ODC), the first and rate-limiting enzyme of polyamine biosynthesis [8].
• 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 [17].
• LoVo cells, grown to about 80% confluence in F-12 medium containing 10% fetal bovine serum, were preincubated for 5 h in low serum medium (1% fetal bovine serum in F-12), and ODC activity was determined by measuring 14CO2 liberated from 14C-labeled ornithine [18].

Regulatory relationships of ODC1

• Epidermal growth factor stimulates ornithine decarboxylase activity in cultured mammalian keratinocytes [13].

Other interactions of ODC1

• Effects of synthetic analogs and fragments of bovine parathyroid hormone on adenosine 3',5'-monophosphate level, ornithine decarboxylase activity, and glycosaminoglycan synthesis in rabbit costal chondrocytes in culture: structure-activity relations [10].
• The influence of epidermal growth factor (EGF) on ornithine decarboxylase has been examined in cultured bovine keratinocytes [13].
• Effects of vasoactive intestinal peptide on adenosine 3',5'-monophosphate, ornithine decarboxylase, and cell growth in a human colon cell line [18].

Analytical, diagnostic and therapeutic context of ODC1

• The bovine ODC mRNA was identified by northern blot to be a single species with a molecular size of 2.35 kilobase pairs [7].
• Molecular cloning of a bovine ornithine decarboxylase cDNA and its use in the detection of restriction fragment length polymorphisms in Holsteins [7].
• In the present study, we used Northern analysis and mobility shift assay to investigate whether ODC gene expression is regulated by androgens in the three human colonic cell lines, SW620, HT-29, and Caco-2 [19].
• ODC-1 was partially purified from human urine with use of reverse-phase HPLC based on the inhibitory effects on [3H]ouabain binding to intact human erythrocytes [20].

References