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)

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 effects of combined administration of bombesin and the ornithine decarboxylase (ODC) inhibitor 1,3-diaminopropane (DAP) on the incidence and number of gastric tumors induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), the ODC activity of the gastric wall and the labelling index of the gastric mucosa were investigated in inbred Wistar rats. Rats were given drinking water containing MNNG (50 micrograms/ml) for 25 weeks and then drinking water containing DAP (2.5 g/l) and/or injections of 40 micrograms/kg body weight of bombesin in depot form every other day. Administration of bombesin alone resulted in significant increases in the incidence of gastric cancers, the ODC activity of the antral portion of the gastric wall and the labelling index of the antral mucosa. Administration of DAP with bombesin significantly reduced enhancement by the latter of gastric carcinogenesis, ODC activity of the antral portion of the gastric wall and the labelling index of the antral mucosa. Our results suggest that ODC inhibition attenuated the enhancement of gastric carcinogenesis by bombesin, and that this enhancement by bombesin was mediated by polyamine biosynthesis.
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PMID:Attenuating effect of ornithine decarboxylase inhibitor (1,3-diaminopropane) on bombesin enhancement of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine. 173 May 25

Polypeptide growth factors that stimulate cell proliferation bind to cell surface receptors and activate intracellular signal transduction pathways. One major signalling pathway, initiated by phosphatidylinositol (PI) turnover, involves activation of protein kinase C. Some polypeptide growth factors, including mitogens that activate protein kinase C, induce a rapid increase in expression of the proto-oncogenes, c-myc and c-fos. In order to characterize the signal transduction pathways responsible for proto-oncogene activation, we treated Swiss 3T3 cells with the tumor promoter phorbol dibutyrate to generate cells deficient in protein kinase C. These cells were then stimulated with platelet extract, bombesin, or epidermal growth factor (EGF) and the levels of c-myc and c-fos mRNA were determined. Platelet extract or bombesin, which stimulate PI turnover, were substantially weaker inducers of c-myc and c-fos mRNA levels in the protein kinase C-depleted cells, although some variability with platelet extract was noted. EGF, which does not stimulate PI turnover in several cell systems, was by contrast a potent inducer of both proto-oncogenes whether or not the cells were deficient in protein kinase C. Pretreatment of cells with phorbol dibutyrate caused little or no change in the basal levels of c-myc or c-fos mRNA, but led to a small but significant increase in basal levels of ornithine decarboxylase mRNA. These results demonstrate that EGF and growth factors that activate PI turnover induce expression of the c-myc and c-fos proto-oncogenes through different pathways.
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PMID:Two independent growth factor-generated signals regulate c-fos and c-myc mRNA levels in Swiss 3T3 cells. 349 94

Enterocyte growth and differentiation occur simultaneously within the epithelium, but little is known regarding any relationship between these two processes. Four rat models of small intestinal epithelial hypo- and hyperplasia (neonatal ontogeny, fasting/refeeding, hypo-/hyperthyroidism, and bombesin treatment) were used to study the regulation of enterocyte gene expression in relation to epithelial growth state. Mucosal scrapings, as well as crypt and villus cell populations, were subjected to Northern blot analyses using radiolabeled cDNA probes corresponding to lactase, intestinal alkaline phosphatase, villin, ornithine decarboxylase (ODC), and the actin control. In all four models, the hypoplastic (atrophic) condition is characterized by high levels of lactase and low levels of the 3.0-kb intestinal alkaline phosphatase mRNA, whereas under hyperplastic conditions this pattern is reversed. The changes in intestinal alkaline phosphatase and lactase are qualitatively similar along the longitudinal axis of the intestine and are proportional to the degree of hyperplasia, as verified by ODC mRNA levels. Furthermore, the crypt-villus axis of differentiation is maintained regardless of epithelial growth state. In conclusion, the pattern of brush-border enzyme gene expression changes as a function of epithelial growth state, indicating a previously unrecognized degree of plasticity to the state of enterocyte differentiation.
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PMID:Pattern of rat intestinal brush-border enzyme gene expression changes with epithelial growth state. 765 20

The effects of combined administration of bombesin (40 micrograms/kg body weight) and the ornithine decarboxylase (ODC) inhibitor, 1,3-diaminopropane (DAP), on the development of large and small intestinal tumors and the incidence of their metastasis to the peritoneum induced by azoxymethane (AOM, 7.4 mg/kg body weight), the ODC activity of the intestinal wall, and the labeling index of the intestinal mucosa and tumor were investigated in inbred Wistar rats. Rats received weekly s.c. injections of AOM for 10 weeks, s.c. injections of bombesin every other day, and drinking water containing DAP (2.5 g/l) until the end of the experiment at week 40. Administration of bombesin significantly increased the incidence of intestinal tumors at week 40. It had no influence on the location, size, histological features or depth of involvement of intestinal adenocarcinomas, but significantly increased the incidence of their metastasis to the peritoneum. It also resulted in a significant increase in the intestinal ODC activity and labeling index. Administration of DAP with bombesin significantly reduced the enhancement of intestinal carcinogenesis by bombesin. Although the combined use of DAP with bombesin had little or no influence on the location, size, histological features, or depth of involvement of intestinal cancers, the incidence of their metastasis was significantly reduced. DAP significantly attenuated bombesin enhancement of the intestinal ODC activity and labeling index. These findings indicate that ODC inhibition attenuated the enhancement of intestinal carcinogenesis and metastasis to the peritoneum.
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PMID:Ornithine decarboxylase inhibitor attenuates bombesin enhancement of intestinal carcinogenesis and metastasis induced by azoxymethane. 805 50

The pancreatic gland has an enormous potential for growth and regeneration, mainly in rodents. These processes remain mostly under the control of the GI hormone cholecystokinin (CCK). The human pancreas however does not show proliferative properties after partial pancreatectomy, but research in this field has been scarce. Recent studies indicate that CCK might not be the expected trophic agent since its two receptors CCK(A) and CCK(B) were not found on human exocrine pancreas. Therefore, if human pancreas grows and regenerates, it has to be under the influence of some unknown trophic factors. Neuropeptides receiving much attention lately as regulators of pancreatic functions could be among the searched trophic agents. This presentation focus on neuropeptides growth potential: GRP-Bombesin, GABA, PP, PYY, Neurotensin, SP, VIP, PACAP, CGRP and galanin. Some neuropeptides have moderate effects on pancreatic enzymes and electrolytes secretion: SP, VIP, PACAP. However, their trophic effects remain unexplored except for GRP-bombesin and PACAP. PACAP preferentially exhibits its mitogenic and proliferative effects on the pancreatic acinar cells AR4-2J via tyrosine kinase, phospholipase D and ornithine decarboxylase activation but not through adenylate cyclase. The growth promoting action of GRP-bombesin is well documented on rodent's pancreas. However, recent studies indicate that this neuropeptide is potentially trophic for larger mammals' pancreas. Indeed, investigators recently documented that bombesin induced pancreatic regeneration in the pig after partial pancreatectomy through mitogen-activated protein kinases activation as do CCK-8 and caerulein on rat pancreas. Have we found the magic pancreatic trophic factor in large mammals? Further investigations will tell.
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PMID:Intervention of GI neuropeptides in pancreatic growth and regeneration: comparison with cholecystokinin. 1507 55