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

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

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.
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PMID:Effect of a tyrosine kinase inhibitor, genistein, on the actions of prolactin in cultured mouse mammary tissues. 131 59

In vivo and in vitro experiments were performed to examine the responsiveness of the gastric mucosa to the growth-promoting action of bombesin in young (4 months) and aged (22 months) Fischer 344 rats. In addition, the role of tyrosine kinase (Tyr-K) in regulating this action of bombesin was also examined. In young rats, infusion of bombesin (300 ng/kg/h) by osmotic minipump for 2 weeks resulted in a significant 100% increase in mucosal DNA synthesis and ornithine decarboxylase (ODC) activity. These increases were accompanied by a 32% (p less than 0.025) rise in gastric mucosal overall Tyr-K activity and a 71% (p less than 0.001) increase in Tyr-k activity associated with pp60c-src, when compared with the corresponding controls. The bombesin-induced stimulation of pp60c-src Tyr-k activity was also associated with a 25% increase in phosphorylation of this protein. In contrast, in aged rats, none of these parameters were affected by bombesin. A similar phenomenon was also observed when mucosal explants from young and aged rats were exposed to bombesin in an organ culture system. Exposure of gastric mucosal explants from young, but not from aged, rats to 10(-8) M bombesin for 8 h resulted in a 300% (p less than 0.001) increase in ODC activity, a 150% (p less than 0.001) rise in Tyr-k activity, and a marked increase (400-600%) in tyrosine-specific phosphorylation of three membrane proteins with M(r) of 55, 44, and 41 kDa, when compared with the corresponding controls. However, these increases were totally abolished by genistein, a specific irreversible inhibitor of Tyr-k.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of tyrosine kinases in bombesin regulation of gastric mucosal proliferative activity in young and aged rats. 143 18

The mucosa of the gastrointestinal tract, including the stomach, undergoes constant renewal. The gastric mucosa is able to regenerate after injury, and this regeneration is associated with increases in epithelial cell proliferation. Gastric epithelial regeneration has been suggested to be impaired with aging. Using a hyperosmolar injury model, we found that gastric epithelial proliferation was markedly lower in aged rats. To elucidate further the regulation of gastric epithelial proliferation after injury, we studied the induction of ornithine decarboxylase and tyrosine kinase. Ornithine decarboxylase is the first and often rate-limiting enzyme in polyamine biosynthesis and tyrosine kinase catalyzes phosphorylation of protein tyrosine residues, and both enzymes have been implicated as important in cell proliferation. We found that hyperosmolar injury induction of ornithine decarboxylase and tyrosine kinase was markedly lower in aged rats. Furthermore, inhibition of ornithine decarboxylase or of tyrosine kinase greatly suppressed gastric epithelial proliferation. Our results confirm that ornithine decarboxylase and tyrosine kinase are important in gastric epithelial proliferation. Further studies of these two enzyme pathways may help elucidate the regulation of gastric epithelial growth and regeneration, particularly the potential alterations with aging.
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PMID:Gastric epithelial cell proliferation after injury. 162 74

Epidemiological and animal studies suggest a role for calcium in the chemoprevention of colorectal neoplasia. This study was designed to investigate whether supplemental oral calcium has a suppressant effect on colonic mucosal ornithine decarboxylase (ODC) and tyrosine kinase activities in patients with adenomatous polyps or a history of adenomatous polyps and whether this is affected by age. ODC and tyrosine kinase activities were measured in rectal mucosal biopsies of 19 male patients (age, years 46-85 years; mean, 66 years) with adenomatous polyps or a history of adenomatous polyps before and after 1 week of calcium supplementation p.o. (CaCO3; 2500 mg/day) and 2 weeks after cessation of calcium treatment. The basal rectal mucosal ODC activity of patients greater than or equal to 64 years old was nearly 4-fold higher than that of patients less than 64 years old (P less than 0.005). In patients greater than or equal to 64 years old, there was a significant decrease in rectal mucosal ODC activity following 1 week of calcium p.o. compared to those age less than 64 years (P less than 0.05). Overall tyrosine kinase activity did not differ significantly in either patient group before or after calcium supplementation p.o. However, the concentration of phosphotyrosine membrane proteins with molecular weights between 40,000 and 60,000 and between 80,000 and 100,000 were suppressed in patients age greater than or equal to 64 years after 1 week of calcium treatment p.o. These patients also had a corresponding decrease in their rectal mucosal ODC activity. Alternatively, patients whose ODC was not affected by calcium showed no apparent change in the relative concentration of rectal mucosal phosphotyrosine membrane proteins. Our data indicate that there is an age-related increase in basal rectal mucosal ODC activity in patients with adenomatous polyps which can be suppressed with calcium supplementation p.o., suggesting a role for dietary calcium in the chemoprevention of colorectal neoplasia.
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PMID:Supplemental calcium suppresses colonic mucosal ornithine decarboxylase activity in elderly patients with adenomatous polyps. 171 10

Hyperplastic polyps are considered to be benign colonic lesions with almost no potential for malignant transformation. Recent reports have shown an increased association of hyperplastic polyps with adenomatous polyps and have advocated a full colonoscopy in patients who harbor hyperplastic polyps. Hyperproliferative mucosa is known to be associated with adenomatous polyps, but its relationship to hyperplastic polyps is unknown. In the present pilot study, it is determined whether a change in mucosal proliferative patterns is observed in patients who harbor only hyperplastic polyps or a history of hyperplastic polyps relative to those who harbor both hyperplastic polyps and adenomatous polyps by measuring ornithine decarboxylase and tyrosine kinase activity in macroscopically normal rectal mucosa. Fifteen patients had either adenomatous polyps proximally or harbored adenomatous polyps and hyperplastic polyps. Seven patients had hyperplastic polyps and 15 patients had a prior history of hyperplastic polyps with no polyps found during the current examination. The ornithine decarboxylase activity of the rectal mucosa with proximal adenomatous polyps or both polyp types was significantly higher than that of hyperplastic polyps, the history of hyperplastic polyps, or controls, and values for hyperplastic polyps and the history of hyperplastic polyps were similar to controls. On the other hand, tyrosine kinase activity in the rectal mucosa of patients with both or either polyp type was elevated without any significant difference between hyperplastic and adenomatous polyps. Thus, it is concluded that although increased ornithine decarboxylase activity in rectal mucosa suggests the presence of adenomatous polyps or a combination of adenomatous with hyperplastic polyps, increased tyrosine kinase activity suggests the presence of any type of polyp.
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PMID:Differential activation of ornithine decarboxylase and tyrosine kinase in the rectal mucosa of patients with hyperplastic and adenomatous polyps. 201 59

We have studied the ability of the neu tyrosine kinase to induce a signal for the activation of cell growth-regulated genes. Serum-starved NIH 3T3 cells expressing an epidermal growth factor receptor (EGF-R)/neu construct encoding a hybrid receptor protein were stimulated with EGF and the activation of the neu tyrosine kinase and stimulation of growth factor inducible genes were followed at the mRNA, protein, and activity levels, and compared to the corresponding responses in the neu proto-oncogene and oncogene expressing cells. Induction of the expression of jun mRNAs was an immediate early effect of EGF stimulation, followed by a marked increase in the biosynthesis of the fos/jun transcription factor complex and an increased transcription factor activity as measured by a recombinant transcription unit using chloramphenicol acetyltransferase assays. In distinction, elevated AP-1/PEA-1 activity in the absence of a significant increase in jun and fos expression was characteristic of the neu oncogene-expressing cells. The glucose transporter mRNA increased at 2 h of EGF stimulation and was associated with enhanced glucose transport of the EGF-treated cells. An increase of ornithine decarboxylase (ODC) mRNA and activity followed these changes. In contrast, serum-starved, EGF-treated neu proto-oncogene- and oncogene-expressing cells showed constitutively low and high glucose transporter and ODC activities, respectively. These findings demonstrate that the chimeric EGF-R/neu receptor is capable of activating the expression of both immediate early genes and biochemical activities associated with cell growth stimulation.
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PMID:Activation of the neu tyrosine kinase induces the fos/jun transcription factor complex, the glucose transporter and ornithine decarboxylase. 257 1

Two in vivo and one in vitro studies were performed to evaluate the chemoprotective role of calcium during the early period of azoxymethane (AOM) induction. In the first set of experiments, groups of male Fischer 344 rats were s.c. injected with either AOM (20 mg/kg) or water (controls) and sacrificed immediately (0 time), and 1, 3, 5, and 7 days postinjection. In the second set of experiments, animals were injected with the same dose of AOM and subsequently pair-fed with rat chow containing either calcium carbonate or diet devoid of added calcium. The amount of calcium consumed was calculated to be 250 mg/kg b.w. In both experiments, colonic mucosa was assayed for ornithine decarboxylase (ODC). In addition, tyrosine kinase (Tyr-k) activity as well as tyrosine specific phosphorylation of membrane proteins were determined. Results revealed that maximal stimulation by AOM of ODC and Tyr-k activity occurred 5 days postinjection. This stimulation was significantly suppressed by calcium. AOM also produced an increase in the rate of tyrosine specific phosphorylation of two distinct colonic mucosal membrane proteins with Mr of 57,000 and 59,000. Again, dietary calcium suppressed the stimulation. In the third set of experiments, organ culture was utilized. Methylazoxymethanol, the active metabolite of AOM, was used instead of AOM in this part of the study. Four hour exposure of mucosal explants to methylazoxymethanol (1 microgram/ml) resulted in a significant (20-30%) increase in ODC and Tyr-k activity when compared to controls. Addition of either CaCl2 (2 mumol/ml) or difluoromethylornithine (2 nmol/ml) the irreversible inhibitor of ODC, significantly suppressed the methylazoxymethanol-induced activity of both ODC and Tyr-k. We conclude that calcium may have a chemoprotective role and tyrosine kinases may have a regulatory role in the early stages of AOM induction of colon cancer.
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PMID:Attenuation of azoxymethane-induced colonic mucosal ornithine decarboxylase and tyrosine kinase activity by calcium in rats. 279 Aug 2

The relationship between tyrosine kinase activity and cellular proliferative activity was investigated in the gastric mucosa. For the purpose of comparison, the liver and the pancreas were also included. Groups of 2-, 14- and 22-month-old male Fischer-344 rats were used. Tyrosine kinase activity was determined in the membrane fraction (30,000 x g pellet) utilizing a synthetic polymer, Glu-Tyr (4:1), as substrate. Cellular proliferative activity was assessed by measuring ornithine decarboxylase in the 20,000 x g supernatant. In all age groups, gastric mucosal tyrosine kinase activity was found to be 10-20-fold higher than in the liver or pancreas. In addition, gastric mucosal tyrosine kinase activity in 22-month-old rats was 35-70% higher than in their 2- and 14-month-old counterparts. Gastric mucosal ornithine decarboxylase activity also followed essentially the same pattern as that of tyrosine kinase in that the highest activity was observed in 22-month-old rats. Increased gastric mucosal proliferative activity in 22-month-old rats was also associated with increased tyrosine-phosphorylation of a mucosal membrane protein with an apparent Mr of 53,000. An opposite phenomenon occurred in the pancreas whose proliferative activity was found to be the lowest. It is concluded that the age-associated changes in gastric mucosal proliferative activity are accompanied by parallel alterations in tyrosine kinase activity. Tyrosine-phosphorylation of a 53 kDa membrane protein may play a role in the regulation of cell proliferation.
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PMID:Gastric mucosal tyrosine kinase activity during aging and its relationship to cell proliferation in rats. 336 54

The insulin and insulin-like growth factor-I (IGF-I) receptors are related heterotetramers consisting of two extracellular ligand-binding alpha-subunits and two transmembrane beta-subunits whose cytoplasmic domains exhibit tyrosine kinase activity. Previous studies have shown that ATP binding by the cytoplasmic tyrosine kinase domains of these receptors is necessary to initiate the signal transduction pathway triggered by ligands or by ligand-mimetic antibodies, suggesting that receptor autophosphorylation is a necessary proximal step in this pathway. In the case of the insulin receptor, it has additionally been demonstrated that a cluster of three tyrosines in the kinase domain itself are the first to be phosphorylated, and that autophosphorylation of these particular residues is necessary for receptor activity. Using stably transfected NIH-3T3 cell lines, we now show that mutation of the analogous residues in the IGF-I receptor abolishes all short, intermediate, and long-term responses to IGF-I. These data suggest that the initial mechanisms of activation of the insulin and IGF-I receptors are very similar. Additionally, we have identified two parameters, induction of c-fos gene expression and ornithine decarboxylase enzyme activity, which are extremely sensitive to IGF-I stimulation and which will be particularly useful in evaluating the biological activity of other mutated versions of the IGF-I receptor.
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PMID:Essential role of tyrosine residues 1131, 1135, and 1136 of the insulin-like growth factor-I (IGF-I) receptor in IGF-I action. 751 94

The pathways regulating ornithine decarboxylase (ODC) activity in the chick embryo were studied to determine which kinase-signaling pathways regulate ODC activity levels during development. Insulin-dependent tyrosine kinase, protein kinase C and cAMP-dependent protein kinase were activated by the addition of insulin, tetradecanoylphorbol-12,13-acetate, and forskolin, respectively. All three drugs increased ODC activity and forskolin combined with insulin increased ODC activity above the increase caused by either drug alone. These results suggest that all three signaling pathways regulate ODC activity during development and that common intermediates exist among the pathways downstream of the kinases.
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PMID:Signaling pathways regulating ornithine decarboxylase activity in the embryonic chicken. 757 28


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