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)

The effects of menhaden oil on the choline-deficient (CD) diet tumor promotion regimen-induced alterations in hepatocyte insulin receptors and the cellular ornithine decarboxylase (ODC) activity have been investigated in this study. Male Sprague-Dawley rats exposed to the tumor-promoting regimen of a CD diet for 10 days showed increases in hepatic ODC activity from 2.68 +/- 0.42 pmol 14CO2/mg protein/h in the animals fed basal control chow (C) to 13.54 +/- 2.38 (P less than 0.02) in the rats fed CD diet. These changes in ODC occur simultaneously with the alterations in hormone receptor binding as reported previously for insulin. Replacement of the lipid present in the control diet with 15% menhaden oil (CMO) had no significant effect on ODC activity (0.91 +/- 0.21), or on the number of insulin receptors (206,000 +/- 37,000) and the Kd (7.4 +/- 1.6). Sequential treatment with 10 days of CD diet and then 10 days of the C diet, resulted in a reversal in the elevated, CD-induced hepatic ODC activity to the control levels; however, substituting 15% menhaden oil for the fat present in the CD diet (CDMO) enhanced this enzymatic activity. In contrast, both sequential and CDMO treatments prevented the insulin receptor alterations induced by the CD diet. These data demonstrate that the CD diet-induced insulin receptor alterations occur concurrently with the induction of ODC activity. But insulin receptor changes and the increased ODC activity are affected differently by CDMO treatment, suggesting that their induction by the CD diet is through distinct mechanisms and only the receptor alterations correspond with the tumor-promoting action of CD diet regimen.
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PMID:The effect of menhaden oil on choline-deficiency-induced hepatic ornithine decarboxylase activity and hepatocyte insulin receptor binding. 218 97

Biological effects of insulin-like growth factors (IGF) I and II on primary cultures of chick embryo liver cells have been investigated and compared 1) with the biological effect of insulin and 2) with competitive binding of the three hormones to their respective binding sites. IGF I and II stimulate the incorporation of D[U-14C]-glucose into liver cell glycogen in a time- and dose-dependent manner, but with a 5-10-fold lower potency than insulin. Both IGFs also lead to enhanced incorporation of 5-[3H]uridine and L[U-14C]valine into trichloroacetic acid (TCA) insoluble material and to activation of ornithine decarboxylase activity. Their potency in stimulating RNA synthesis and ornithine decarboxylase activity is comparable to that of insulin. Protein synthesis is maximally stimulated at 3 nM by all three hormones. In the competitive binding studies, IGF I and II are 10-fold less potent than insulin in competing for [125I]insulin binding, but 100-fold more potent than insulin in competing for [125I]IGF I or II binding. These studies show that IGF I and II stimulate the same metabolic indices as insulin in the chick embryo liver. By comparing these biological effects with competitive binding data it appears that IGFs act on glucose metabolism in the chick embryo liver via the insulin receptor, whereas stimulation of growth indices by IGFs and insulin appears to be mediated by their own specific receptors.
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PMID:Effects of insulin-like growth factors on chick embryo hepatocytes. 257 20

The activation of protein kinase C and protein phosphorylation by tumor promoters were examined using quiescent cultures of BALB/3T3 and C3H/10T1/2 cells, because in these cells tumor promoters enhance chemically induced transformation and also induce DNA synthesis and ornithine decarboxylase. The cytosol and membrane fractions were partially purified, and the activity of protein kinase C was assayed. In quiescent cells, protein kinase C activity was found only in the cytosol fraction. Treatment with 100 ng of 12-O-tetradecanoylphorbol-13-acetate or teleocidin B per ml caused rapid translocation of protein kinase C from the cytosol to the membrane fraction. The activity in the cytosol disappeared almost completely after 15 min when the activity in the membrane reached a peak. The membrane activity gradually decreased to the control level after 6 h, while no activity reappeared in the cytosol within 6 h. Under these circumstances, a membrane protein with a molecular weight of 90,000 and pl of 4.0-4.4 (termed p90) was specifically phosphorylated, possibly by the activated protein kinase C, in both cell-free and intact-cell systems. On treatment of quiescent BALB/3T3 cells with 100 ng of 12-O-tetradecanoylphorbol-13-acetate, p90 phosphorylation increased 2-fold in 1 min, reaching a peak in 15 min of 3.4-fold the initial value. The phosphorylation of p90 increased with increase in the concentrations of 12-O-tetradecanoylphorbol-13-acetate between 0.1 and 10 ng/ml and reached a plateau at 10 ng/ml. p90 phosphorylation also occurred on exposure of the cells to non-phorbol ester tumor promoters (mezerein and teleocidin B) and growth factors, such as platelet-derived growth factor and fibroblast growth factor. p90 was not immunoprecipitated by antibody against the insulin receptor. Phosphorylation of p90 occurred at a serine residue. The present study suggests that activation of protein kinase C and phosphorylation of p90 by it are early events leading to tumor promotion.
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PMID:Activation of protein kinase C and specific phosphorylation of a Mr 90,000 membrane protein of promotable BALB/3T3 and C3H/10T1/2 cells by tumor promoters. 308 Feb 29

Binding of 125I-insulin to cells cultured from the skin of nondiabetic and diabetic (db/db) mice was 80 to 90% specific, time- and temperature-dependent, and maximal at pH 8.0. Porcine insulin and desalanine insulin competed equally for 125I-insulin binding, while proinsulin and desoctapeptide insulin were 35% and 20% as potent, respectively. 125I-Insulin dissociated from both types of fibroblasts with a T 1/2 of 7.5 min. Analysis of the dissociation data resolved two rate constants of 3.0 and 1.0 X 10(-4) s-1 for nondiabetic, and 2.0 and 0.8 X 10(-4) s-1 for diabetic fibroblasts. Binding of 125I-insulin to diabetic fibroblasts was 35 to 50% of that to nondiabetic fibroblasts during at least 17 passages. Scatchard analysis of the binding data resolved high (K1 = 2 X 10(10( M-1) and low affinity K2 = 2 X 10(9) M-1) sites. Nondiabetic fibroblasts possessed 7.7 X 10(4) sites/cell, while diabetic fibroblasts possessed 2.9 X 10(4)/cell. Incubation of nondiabetic fibroblasts with insulin resulted in a time- and concentration-dependent decrease in the binding of 125I-insulin. Binding activity returned to normal when insulin was removed and it was prevented by cycloheximide. In contrast, diabetic fibroblasts did not exhibit down-regulation of receptors. A half-maximal and maximum (85%) stimulation of 2 deoxy-D-glucose uptake was observed with 0.75 nM and 16.7 nM insulin in nondiabetic fibroblasts. In contrast, diabetic cultures required 3.5 nM insulin for half-maximal stimulation of 2 deoxy-D-glucose uptake, and maximum stimulation was 32% with 16.7 nM insulin. Similarly, diabetic fibroblasts required higher concentrations of insulin (20 nM) to stimulate ornithine decarboxylase activity to 42% of nondiabetic cells. These results indicate that in comparison with fibroblastic cultures from nondiabetic animals, those from diabetic animals expressed differences in insulin receptor numbers which are maintained in culture over many generations and are accompanied by diminished insulin responses.
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PMID:Fibroblastic cultures from the diabetic db/db mouse. Demonstration of decreased insulin receptors and impaired responses to insulin. 699 11

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

Although insulin is known to be an important generator of regulatory signals during fetal growth and development, neither the immediate nor long-term effects of alcohol (ethanol) on insulin action are well understood. In the rat, fetal exposure to alcohol has been shown to be correlated with a subsequent abnormal response to a glucose load in the neonate and adult. Further, fetal hypoplasia secondary to maternal alcohol consumption is correlated with decreased placental glucose transport and with a lowering of the glucose levels in fetal tissues. However, the fetal effects of alcohol cannot be completely overcome by glucose/caloric supplementation, suggesting that factors other than glucose transport are involved. Using an embryonic chick model that negates the factors of maternal/placental metabolism and transport, the current study found that fetal alcohol exposure markedly increased insulin binding in developing tissue, but had little effect on the binding of the insulin-like growth factors. Competitive binding experiments revealed a marked increase in insulin receptor numbers, but no change in binding affinity as a result of the alcohol exposure. Basal uptake of 2-deoxyglucose by fetal tissue was lowered by alcohol exposure, but incubation with exogenous porcine insulin (1 x 10(-7) M) resulted in a significant increase in glucose uptake by the alcohol-exposed embryos. The increases in insulin binding and in insulin-dependent glucose uptake notwithstanding, exogenous insulin could not induce normal levels of ornithine decarboxylase activity in embryonic cells previously exposed to alcohol.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin signaling in chick embryos exposed to alcohol. 757 96

Fetal growth suppression associated with chronic maternal intake of cigarette smoke is frequently observed in humans and studies using animal models suggest that in utero nicotine exposure is an important component of this growth suppression. The developing fetal central nervous system (CNS) is sensitive to the growth inhibitory effect of nicotine and morphological as well as functional CNS deficits may result from fetal nicotine exposure. The studies presented here show that nicotine exposure during early embryonic development ultimately inhibits the ability of 7-11 day old chicks to learn a detour task. The brain growth suppression caused by nicotine is paralleled by a failure of the early embryo brain to express the normal developmental increase in ornithine decarboxylase (ODC) activity. This biochemical change may be germane to the mechanism of nicotine-induced growth inhibition and/or nicotine-induced behavioral changes because the appropriate expression of ODC activity is essential to normal growth and differentiation in the fetal CNS. In the chick embryo, nicotine exposure alters several important signaling pathways that regulate ODC expression. For example, nicotine exposure lowers embryonic brain glucose levels and causes significant decreases in whole brain cyclic adenosine 3',5'-monophosphate (cyclic AMP) levels and in cyclic AMP binding proteins (protein kinase-A regulatory activity). Also, in cultured chick cells, nicotine inhibits the ability of a potent mitogen (insulin) to induce ODC activity, but, paradoxically, in ovo nicotine exposure increased insulin binding and stimulated insulin receptor autophosphorylation in brain membranes.
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PMID:Biochemical changes, early brain growth suppression and impaired detour learning in nicotine-treated chicks. 769 78

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