Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The polyamine biosynthetic enzymes, ornithine decarboxylase (EC 4.1.1.17) (ODC) and arginine decarboxylase (EC 4.1.1.19) (ADC), are negatively controlled by cAMP in Escherichia coli. The specific activities of ODC and ADC were determined in crude extracts prepared from E. coli strains carrying a mutation in the adenylate cyclase (EC 4.6.1.1) structural gene (cya) and wildtype strains. These strains were cultured on various carbon sources in the presence and absence of cAMP. In wild-type strains, ODC and ADC activities were diminished in cells grown on glycerol compared to these strains cultured on glucose. When cya strains were grown on glucose or glycerol, ODC and ADC activities were the same. Addition of 1 mM cAMP to glucose-based medium repressed ODC and ADC activities in both the wild-type and cya strains. Furthermore, cAMP exerts its negative control through the cAMP receptor protein, since strains carrying a mutation in the crp structural gene fail to repress ODC and ADC activities in response to increased cAMP obtained by carbon source manipulation or cAMP supplementation of the growth medium. This evidence suggests that negative control of ODC and ADC by cAMP occurs at the level of transcription.
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PMID:Negative control of ornithine decarboxylase and arginine decarboxylase by adenosine-3':5'-cyclic monophosphate in Escherichia coli. 629 Aug 46

PC12 cells, a nerve growth factor-responsive clone of rat pheochromocytoma, contain a membrane-bound adenylate cyclase, which can be activated by adenosine analogs. The characteristics of the cyclase response indicate the presence of stimulatory adenosine receptors. Adenosine analogs also produce a marked increase in the ornithine decarboxylase levels of the cells, and the characteristics of this response suggest that it is linked to the adenylate cyclase-stimulatory adenosine receptors. The ornithine decarboxylase response elicited by 5'-N-ethylcarboxamideadenosine (NECA), a potent stimulatory adenosine analog, is synergistic with that produced by nerve growth factor. Differentiation of the cells with nerve growth factor, however, does not substantially alter either the response of cyclase to the adenosine analog or the magnitude of the adenosine-evoked ornithine decarboxylase response. Treatment of the cells with NECA produces an increase in the phosphorylation of a specific non-histone nuclear protein. While causing little or no morphological alteration by itself, NECA is synergistic with nerve growth factor in producing neurite outgrowth in PC12 cells. NECA does not cause an induction of acetylcholinesterase in the cells. NECA does not cause an induction of acetylcholinesterase in the cells, nor does it appear to affect the induction of this enzyme by nerve growth factor.
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PMID:The action of adenosine analogs on PC12 cells. 733 72

We have tested the hypothesis that H-ras transformed cells contain alterations in signal pathways important in controlling the expression of ornithine decarboxylase (ODC), the highly regulated rate-limiting activity in the biosynthesis of polyamines. Mouse 10T1/2 fibroblasts and a series of 10T1/2 H-ras transformed cell lines were treated with stimulators of cAMP synthesis (forskolin and cholera toxin), a biologically stable analogue of cAMP (8-bromo-cAMP), and an inhibitor of cAMP degradation (3-isobutyl-1-methylxanthine). Elevations in ODC gene expression were noted in H-ras transformed cells that were not observed in parental 10T1/2 fibroblasts. The forskolin-mediated effects were not detected with 1,9-dideoxyforskolin, a compound structurally related to forskolin, which does not activate adenyl cyclase. The effects observed with cholera toxin were not detected when cells were treated with the purified subunits of this compound, indicating that the toxin-induced effects were cAMP-specific. Actinomycin D treatment prior to forskolin exposure reduced the elevation observed in ODC gene expression indicating the involvement of the transcriptional process. Furthermore, we observed that cycloheximide treatment of malignant but not benign H-ras transformed cells significantly elevated ODC message level. Treatment of malignant cells with both cycloheximide and forskolin together resulted in a further additive elevation in ODC message, but a similar treatment of benign tumor cells reduced the forskolin-mediated increase in ODC message. In addition, treatment of H-ras transformed cells with the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA) led to an elevation in ODC mRNA levels not observed in parental 10T1/2 fibroblasts.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ornithine decarboxylase gene expression is aberrantly regulated via the cAMP signal transduction pathway in malignant H-ras transformed cell lines. 752 12

Neurotransmitters act as trophic factors during brain development, regulating expression of genes that control cellular differentiation. One example of this trophism is the beta adrenergic signaling cascade: activation of beta receptors leads sequentially to increased cyclic AMP (cAMP), augmented expression of the nuclear transcription factor, c-fos, and induction of ornithine decarboxylase (ODC), an enzyme obligatory for neuronal development. After neonatal lesioning of noradrenergic nerves with 6-hydroxydopamine (6-OHDA), beta receptors become uncoupled from ODC induction in the cerebellum, a region that undergoes its peak of cell replication/differentiation postnatally. The present study investigates the mechanism for uncoupling of beta receptors from response elements. In the cerebellum, 6-OHDA had minor effects on beta receptor binding capabilities and caused slight supersensitivity of the beta adrenergic response of adenylate cyclase; the latter reflected increased expression of cyclase catalytic subunits, rather than a specific effect on beta receptor coupling. In contrast, the linkage of cAMP to cerebellar c-fos expression showed marked deficiencies in lesioned animals and a corresponding loss of the ability of beta receptors to induce c-fos; accordingly, this is a likely point at which beta adrenergic control of ODC is programmed by neuronal input. A critical period exists for neurotrophic influence: the alterations persisted past the point at which cerebellar norepinephrine levels recovered, and comparable effects did not occur in earlier-developing regions. In the forebrain, for example, neonatal lesions produced receptor upregulation and supersensitivity of c-fos to cAMP stimulation. These results suggest that presynaptic input is vital in programming beta adrenergic responsiveness during a critical period of development, and that interruption of transsynaptic events occurring at this time can lead to lasting alterations in neuronal differentiation and responsiveness.
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PMID:Role of presynaptic input in the ontogeny of adrenergic cell signaling in rat brain: beta receptors, adenylate cyclase and c-fos protooncogene expression. 771 97

In adulthood, thyroid hormone regulates beta adrenergic responsiveness. We addressed whether similar processes operate in the developing brain, thus playing a role in neurotransmitter control of target cell differentiation. Rats were made hyperthyroid [triiodothyronine (T3)] or hypothyroid [propylthiouracil (PTU)] during the immediate perinatal period, and the development of beta adrenergic signal transduction was evaluated in three brain regions. PTU treatment resulted in an ubiquitous deficit in the number of beta receptor binding sites. Although beta adrenergic stimulation of adenylate cyclase activity was also obtunded by PTU, the effects were much less prominent and were restricted to one region (forebrain); comparison with basal adenylate cyclase and with total enzymatic activity (forskolin stimulation) indicated that the differences in isoproterenol response were at the level of adenylate cyclase expression, rather than in specific receptor coupling. PTU also reduced responsiveness of ornithine decarboxylase (ODC), a key enzyme that couples receptors to differentiation, again, changes in receptor-mediated responsiveness reflected alterations in total enzyme activity, rather than effects on receptor coupling. In contrast, measurements of c-fos, a protooncogene that couples cyclic AMP to induction of ODC, showed increased responses to beta adrenergic or cyclic AMP stimulation in PTU-treated animals. The effect of PTU on c-fos responsiveness occurred in the absence of alterations in basal c-fos expression, a situation different from that seen with adenylate cyclase or ODC. T3 administration had only small effects on any of these variables. The role of thyroid hormones thus involves targeting of beta receptors and receptor-mediated stimulation of nuclear transcription factors (c-fos), as well as basal expression of transduction components in the signalling cascade (adenylate cyclase, ODC). The effects of PTU, contrasted with the failure of T3 to enhance development of beta receptors or their transduction components, suggest that thyroid hormone is obligatory for normal development of this pathway, but that endogenous hormone levels are already optimally permissive.
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PMID:Role of thyroid status in the ontogeny of adrenergic cell signaling in rat brain: beta receptors, adenylate cyclase, ornithine decarboxylase and c-fos protooncogene expression. 796 48

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

Candida albicans generally grows in hyphae form in RPMI1640 medium. However, addition of 1,4-diamino-2-butanone (DAB), a competitive inhibitor of ornithine decarboxylase, decreased the amount of polyamines in C. albicans, and induced the proliferation of the C. albicans yeast form. The expression of CYR1 mRNA was significantly inhibited by the addition of DAB compared with that of the control. The amount of intracellular cAMP was also decreased by the addition of DAB. A specific adenylate cyclase inhibitor, cis-N-[2-phenylcyclopentyl]-azacyclotridec-1-en-2-amine (MDL-12,330A) promoted the growth of the yeast form. These results indicated that polyamines exist upstream of the adenylate cyclase-cAMP signal pathway and regulate the transformation of C. albicans.
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PMID:Hyphae formation of Candida albicans is regulated by polyamines. 1518 39


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