scholarly journals Effect of inhibition of polyamine synthesis on the content of decarboxylated S-adenosylmethionine

1982 ◽  
Vol 202 (2) ◽  
pp. 519-526 ◽  
Author(s):  
Anthony E. Pegg ◽  
Hannu Pösö ◽  
Kay Shuttleworth ◽  
Richard A. Bennett
Keyword(s):  
Partial Hepatectomy ◽  
Ornithine Decarboxylase ◽  
Rat Liver ◽  
Adenine Nucleotides ◽  
3T3 Cells ◽  
Direct Inhibition ◽  
Polyamine Synthesis ◽  
Mouse Fibroblasts ◽  
Regenerating Rat Liver ◽  
Specific Inhibitors

1. The content of decarboxylated S-adenosylmethionine (AdoMet) in transformed mouse fibroblasts (SV-3T3 cells) was increased 500-fold to about 0.4fmol/cell when ornithine decarboxylase was inhibited by α-difluoromethylornithine. This increase was due to the absence of putrescine and spermidine, which serve as substrates for aminopropyltransferases with decarboxylated AdoMet as an aminopropyl donor, and to the enhanced activity of AdoMet decarboxylase brought about by depletion of spermidine. The increase in decarboxylated AdoMet content was abolished by addition of putrescine, but not by 1,3-diaminopropane. 2. 5′-Methylthiotubercidin also increased decarboxylated AdoMet content, presumably by direct inhibition of aminopropyl-transferase activities, but the increase in its content and the decline in spermidine content were much less than those produced by α-difluoromethylornithine. 3. Decarboxylated AdoMet content of regenerating rat liver was measured in rats treated with inhibitors of ornithine decarboxylase. The content was increased by 60% 32h after partial hepatectomy in control rats, by 90% when α-difluoromethylornithine was given to the partially hepatectomized rats, and by 330% when 1,3-diaminopropane was used to inhibit putrescine and spermidine synthesis. After 48h of exposure to 1,3-diaminopropane, which completely prevented the increase in spermidine after partial hepatectomy, there was a 5-fold rise in hepatic decarboxylated AdoMet concentration. These increases were prevented by treatment with putrescine or with methylglyoxal bis(guanylhydrazone), an inhibitor of AdoMet decarboxylase. 4. These results show that changes in AdoMet metabolism result from the administration of specific inhibitors of polyamine synthesis. The possible consequences of the accumulation of decarboxylated AdoMet, which could, for example, interfere with normal cellular methylation or lead to depletion of cellular adenine nucleotides, should be considered in the interpretation of results obtained with such inhibitors.

scholarly journals Inhibition of polyamine accumulation and deoxyribonucleic acid synthesis in regenerating rat liver

1976 ◽  
Vol 158 (2) ◽  
pp. 485-488 ◽  
Author(s):  
H Pösö ◽  
J Jänne
Keyword(s):  
Partial Hepatectomy ◽  
Ornithine Decarboxylase ◽  
Rat Liver ◽  
Deoxyribonucleic Acid ◽  
Acid Synthesis ◽  
Liver Protein ◽  
Polyamine Synthesis ◽  
Total Liver ◽  
Regenerating Rat Liver ◽  
Deoxyribonucleic Acid Synthesis

Repeated injections of 1,3-diaminopropane into rats after partial hepatectomy caused a repression-type inhibiton of liver ornithine decarboxylase (EC 4.1.1.17) and totally prevented the marked increases in liver putrescine and spermidine concentrations that normally occur in response to partial hepatectomy. The inhibition of polyamine synthesis by diaminopropane was accompanied by a profound decrease (about 80%) in the synthesis of DNA in the regenerating rat liver without any changes in the synthesis of RNA and total liver protein.

DEOXYCYTIDYLATE DEAMINASE LEVELS IN REGENERATING RAT LIVER

1961 ◽  
Vol 39 (6) ◽  
pp. 1043-1054 ◽  
Author(s):  
D. K. Myers ◽  
C. Anne Hemphill ◽  
Constance M. Townsend
Keyword(s):  
Dna Synthesis ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Rat Liver ◽  
Deoxyribonucleic Acid ◽  
Regenerating Liver ◽  
Regenerating Rat Liver ◽  
High Level ◽  
Early Regeneration

Deoxycytidylate deaminase activity and net synthesis of deoxyribonucleic acid (DNA) in vivo were found to increase at approximately the same time during the early stages of liver regeneration. However, deaminase activity in the regenerating liver remained at a high level for 1 day after DNA synthesis had slowed down again during the later stages of regeneration. The increase in deaminase activity was restricted as a result of exposure to 600 r X radiation during early regeneration, but this effect only became evident 11–16 hours after the irradiation. Irradiation on the second day after partial hepatectomy, when deaminase levels in control regenerating livers were relatively constant, failed to affect the deaminase activity immediately but did produce a 40–50% decrease in activity 11–16 hours later. Other antimitotic agents, e.g., colchicine, had little effect on deaminase activity.

Upregulation of Escherichia coli heat-stable enterotoxin receptor in regenerating rat liver

1994 ◽  
Vol 266 (5) ◽  
pp. G899-G906 ◽  
Author(s):  
D. W. Laney ◽  
J. A. Bezerra ◽  
J. L. Kosiba ◽  
S. J. Degen ◽  
M. B. Cohen
Keyword(s):  
Escherichia Coli ◽  
Mrna Expression ◽  
Partial Hepatectomy ◽  
Rat Liver ◽  
Acute Phase ◽  
Chloride Secretion ◽  
Hepatocyte Proliferation ◽  
Heat Stable ◽  
Hepatocyte Regeneration ◽  
Regenerating Rat Liver

Guanylate cyclase C (GC-C) is a transmembrane protein that serves as a receptor for the recently characterized endogenous ligand guanylin and for Escherichia coli heat-stable toxin (STa). Binding of either guanylin or STa to intestinal GC-C results in net chloride secretion. Although GC-C is expressed in the rat intestine throughout life, its expression in the rat liver has previously been shown to occur only during the perinatal period. As a step toward elucidating the role of this receptor in the liver, we tested the hypothesis that GC-C mRNA expression could be induced in the adult rat liver following 1) partial hepatectomy, a stimulus for hepatocyte proliferation; 2) intraperitoneal carbon tetrachloride injection, a model of hepatocyte regeneration in the presence of inflammatory changes; and 3) subcutaneous turpentine injection, which generates an acute phase response without hepatocyte proliferation. We demonstrated expression of GC-C mRNA in the regenerating rat liver following either partial hepatectomy or CCl4-induced hepatic necrosis. We have also shown that GC-C mRNA expression occurred in association with an acute phase reaction. Coordinate with the expression of GC-C mRNA, there was upregulation of radiolabeled STa binding to liver plasma membranes prepared from turpentine-treated rats. Maximal expression of GC-C occurred in preparations enriched for the canalicular domain. Although the function of GC-C in the liver is unknown, localization to the canalicular domain would be consistent with a role for GC-C in hepatic chloride secretion, especially in the perinatal liver and during hepatocyte regeneration.

scholarly journals Dissociation of tumour-promoter-induced effects on prostaglandin release, polyamine synthesis and cell proliferation of 3T3 cells

1981 ◽  
Vol 194 (3) ◽  
pp. 975-982 ◽  
Author(s):  
R Lanz ◽  
K Brune
Keyword(s):  
Cell Proliferation ◽  
Ornithine Decarboxylase ◽  
Thymidine Incorporation ◽  
Decarboxylase Activity ◽  
3T3 Cells ◽  
Polyamine Synthesis ◽  
Ornithine Decarboxylase Activity ◽  
Proliferative Effect ◽  
Prostaglandin Release ◽  
Anti Inflammatory

The phorbol ester 12-O-tetradecanoylphorbol 13-acetate induces tumour promotion, inflammation, cell proliferation and prostaglandin release. Recent reports suggest that the prostaglandins released by 12-O-tetradecanoylphorbol 13-acetate (TPA) initiate a cascade of events leading to polyamine synthesis and cell proliferation. In experiments designed to test this contention, it was found that addition of TPA (1 microM to 1 nM) to confluent mouse 3T3 fibroblasts successively caused the release of prostaglandins E2 and I2, induction of the enzyme ornithine decarboxylase (EC 4.1.1.17), stimulation of [3H]thymidine incorporation into DNA, and cell proliferation. Pretreatment of the cells with the anti-inflammatory steroid dexamethasone (1 microM) or the non-steroidal anti-inflammatory drug indomethacin (1 microM) inhibited TPA-induced prostaglandin release. However, dexamethasone enhanced the other effects of TPA, whereas indomethacin was ineffective. Addition of prostaglandin E2 to the cultures did not induce ornithine decarboxylase activity and cell proliferation. Pretreatment of the cells with 1,3-diaminopropane (1 mM) or alpha-methylornithine (5 mM), inhibitors of polyamine synthesis, decreased TPA-induced ornithine decarboxylase activity without affecting DNA synthesis. TPA stimulated [3H]thymidine incorporation into DNA, even when the ornithine decarboxylase activity was completely blocked. These data suggest that the proliferative effect of TPA on 3T3 cells is independent of prostaglandin release and polyamine synthesis.

scholarly journals Thymidine metabolism in regenerating rat liver one to two hours after partial hepatectomy

1973 ◽  
Vol 136 (3) ◽  
pp. 571-577 ◽  
Author(s):  
Margery G. Ord ◽  
Lloyd A. Stocken
Keyword(s):  
Partial Hepatectomy ◽  
Intravenous Injection ◽  
Rat Liver ◽  
Thymidine Uptake ◽  
Regenerating Rat Liver ◽  
Perfusion Studies ◽  
Saturation Kinetics

1. When [3H]thymidine was injected intravenously into rats in amounts up to 40mg/kg body wt. and the3H radioactivity in the livers measured at 30min, saturation kinetics for thymidine uptake were not found. If the animals were examined 3 min after intravenous injection, saturation could be attained in normal rats with 12mg of thymidine/kg and in partially hepatectomized rats with 4mg/kg. At concentrations of thymidine close to saturation, no differences were found in rate or amount of uptake/g of liver between normal and partially hepatectomized rats 1–2h after operation. 2. Perfusion techniques were used to compare thymidine uptakes in the two sets of rats at concentrations up to 40μm-thymidine. Uptakes with tracer amounts of thymidine after 30min were identical in vivo and in the perfusion studies and were twice as great in livers from partially hepatectomized rats with concentrations up to 40μm-thymidine. 3. At 1.5h after operation there was nearly twice as much β-aminoisobutyrate present per g of liver from partially hepatectomized as compared with normal rats.

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