Chen, C, Young, B A, Coleman, C S, Pegg, A E, Sheppard, D
T he integrin alpha9beta1 is expressed on migrating cells, such as leukocytes, and binds to multiple ligands that are present at sites of tissue injury and inflammation. alpha9beta1, like the...
Dolan, M E, Moschel, R C, Pegg, A E
O6-Alkylguanine-DNA alkyltransferase was rapidly and irreversibly inactivated by exposure to O6-benzylguanine or the p-chlorobenzyl and p-methylbenzyl analogues. This inactivation was much more rapid...
Repair of O-alkylpyrimidines in mammalian cells: a present consensus.
Brent, T P, Dolan, M E, Fraenkel-Conrat, H, Hall, J, Karran, P, Laval, L, ...
Enzymatic repair of the O-alkylpyrimidines (O2- and O4-alkylthymine, O2-alkylcytosine) and alkyl phosphotriesters has been studied in Escherichia coli, and the two proteins involved, a glycosylase...
Enzymatic release of 7-methylguanine from methylated DNA by rodent liver extracts.
Rat and hamster liver extracts were found to contain DNA glycosylases capable of removing 3-methyladenine and 7-methylguanine from methylated DNA. The activity of 7-methylguanine-DNA glycosylase was...
Removal of O6-methylguanine from DNA by human liver fractions.
Pegg, A E, Roberfroid, M, Von Bahr, C, Foote, R S, Mitra, S, Bresil, H, ...
In in vitro assays using methylated DNAs as substrates, human liver fractions were shown to be able to catalyze the removal of O6-methylguanine. The amount of removal was proportional to the amount...
Swenberg, J A, Bedell, M A, Billings, K C, Umbenhauer, D R, Pegg, A E
The activity of the alkyl acceptor protein (AAP) responsible for repair of DNA containing the promutagenic lesion O6-alkylguanine was determined in hepatocytes and nonparenchymal cells (NPC) obtained...
Pegg, A E, Pakala, R, Bergeron, R J
Treatment of Chinese-hamster ovary (CHO) cells with N1N11-bis(ethyl)norspermine (BENSM) led to a very large increase in the activity of spermidine/spermine N1-acetyltransferase (SAT), which rose by...
Porter, C W, Pegg, A E, Ganis, B, Madhabala, R, Bergeron, R J
In the present study, the spermine (SPM) analogue N1N12-bis(ethyl)spermine (BESPM) is compared with SPM in its ability to regulate ornithine decarboxylase (ODC) and S-adenosyl-L-methionine...
Casero, R A, Celano, P, Ervin, S J, Wiest, L, Pegg, A E
The cytotoxic response of the human large cell lung carcinoma line NCI H157 to exposure to the polyamine analogue N1 N12-bis(ethyl)spermine (BESpm) is preceded by an extremely high induction of...
Shantz, L M, Holm, I, Jänne, O A, Pegg, A E
The effects of addition of exogenous spermidine and spermine and of two inhibitors of polyamine biosynthesis, alpha-difluoromethylornithine (DFMO), which decreases spermidine concentrations, and...
Byers, T L, Wiest, L, Wechter, R S, Pegg, A E
We have previously reported that prolonged chronic exposure to the S-adenosyl-L-methionine decarboxylase (AdoMetDC) inhibitor, 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxy-adenosine (MDL 73811,...
Albanese, L, Bergeron, R J, Pegg, A E
N1N12-Bis(ethyl)spermine (BESM) and related compounds are powerful inhibitors of cell growth that may have potential as anti-neoplastic agents [Bergeron, Neims, McManis, Hawthorne, Vinson, Bortell...
Byers, T L, Ganem, B, Pegg, A E
The effects of inhibition of the capacity to form spermidine and spermine on cell growth were investigated using murine leukaemia L1210 cells and...
Effect of 1-amino-oxy-3-aminopropane on polyamine metabolism and growth of L1210 cells.
Poulin, R, Secrist, J A, Pegg, A E
1-Amino-oxy-3-aminopropane (AOAP) was reported to inhibit several mammalian polyamine-biosynthetic enzymes in vitro, including ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase...
Expression of a human gene for polyamine transport in Chinese-hamster ovary cells.
Byers, T L, Wechter, R, Nuttall, M E, Pegg, A E
A molecular-genetic approach towards isolating mammalian polyamine-transport genes and their encoded proteins was devised involving the production of Chinese-hamster ovary (CHO) cells expressing a...
Madhubala, R, Secrist, J A, Pegg, A E
Treatment of L1210 cells with either of two inhibitors of S-adenosylmethionine decarboxylase (AdoMetDC), namely 5'-deoxy-5'-[N-methyl-N-[2-(amino-oxy)ethyl])aminoadenosine or...
Nagarajan, S, Ganem, B, Pegg, A E
A number of synthetic polyamine derivatives that included five achiral gem-dimethylspermidines and two analogous tetramethylated spermines were tested for their abilities to serve as substrates for...
Poulin, R, Pelletier, G, Pegg, A E
Deregulation of polyamine transport in L1210 cells overexpressing ornithine decarboxylase leads to a lethal accumulation of spermidine. We now provide evidence that over-accumulation of natural and...
Polyamines play major roles in ionic and osmotic regulation, but their exact involvement in specific ion transport processes is poorly defined. Treatment of L1210 mouse leukaemia cells with either 5...
Parry, L, Balaña Fouce, R, Pegg, A E
Spermidine/spermine N1-acetyltransferase (SSAT) is the rate-limiting enzyme for the degradation and excretion of polyamines in mammalian cells, and its activity is known to be increased enormously on...
Shantz, L M, Viswanath, R, Pegg, A E
S-Adenosylmethionine decarboxylase (AdoMetDC), a rate-limiting enzyme in polyamine biosynthesis, is regulated by polyamines at the levels of both transcription and translation. Two unusual features...
Byers, T L, Lakanen, J R, Coward, J K, Pegg, A E
The abilities of the natural polyamines, spermidine and spermine, and of the synthetic analogues, 1-methylspermidine and 1,12-dimethylspermine, to reverse the effects of the S-adenosyl-L-methionine...
Byers, T L, Wechter, R S, Hu, R H, Pegg, A E
The regulation of polyamine transport and the roles of polyamine transport and synthesis in cell growth were investigated using cultured Chinese hamster ovary (CHO) cells and CHOMG cells which are...
Holm, I, Persson, L, Pegg, A E, Heby, O
The rate-limiting enzymes in polyamine biosynthesis, ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC), are negatively regulated by the polyamines spermidine and...
The effects of alpha-difluoromethylornithine, a specific inhibitor of ornithine decarboxylase, on cell growth rate, polyamine content and the content of decarboxylated S-adenosylmethionine in SV-3T3...
Comparison of ornithine decarboxylase from rat liver, rat hepatoma and mouse kidney.
Seely, J E, Persson, L, Sertich, G J, Pegg, A E
Comparisons were made of ornithine decarboxylase isolated from Morris hepatoma 7777, thioacetamide-treated rat liver and androgen-stimulated mouse kidney. The enzymes from each source were purified...
Exposure of rat L6 cells in culture to exogenous polyamines led to a very large increase in the activity of spermidine/spermine N1-acetyltransferase. Spermine was more potent than spermidine in...
Decarboxylation of alpha-difluoromethylornithine by ornithine decarboxylase.
Pegg, A E, McGovern, K A, Wiest, L
The mechanism of inactivation of rodent ornithine decarboxylase by alpha-difluoromethylornithine (DFMO) was studied using the inhibitor labelled with 14C in both the 1 and the 5 positions....
Porter, C W, Berger, F G, Pegg, A E, Ganis, B, Bergeron, R J
Polyamine biosynthesis in intact cells can be exquisitely controlled with exogenous polyamines through the regulation of rate-limiting biosynthetic enzymes, particularly ornithine decarboxylase...
Effect of putrescine on the synthesis of S-adenosylmethionine decarboxylase.
The synthesis of S-adenosylmethionine (AdoMet) decarboxylase was studied by translating the rat prostate mRNA for this enzyme in a reticulocyte lysate. The protein was formed as a precursor of Mr...
Pegg, A E, Wechter, R, Pajunen, A
Treatment of SV-3T3 cells with the spermine synthase inhibitor S-methyl-5'-methylthioadenosine [AdoS+(CH3)2] led to a large increase in the activity of S-adenosylmethionine decarboxylase (AdoMetDC)...
Pegg, A E, Nagarajan, S, Naficy, S, Ganem, B
Synthetic unsaturated analogues of the natural polyamine were examined as possible substrates for spermine synthase and as replacements for spermidine in supporting the growth of SV-3T3 cells. It was...
Comparison of inhibitors of S-adenosylmethionine decarboxylase from different species.
S-Adenosyl-L-methionine decarboxylases were purified from rat ventral prostate, yeast (Saccharomyces cerevisiae), slime mould (Physarum polycephalum) and bacteria (Escherichia coli) and tested for...
Studies of the specificity and kinetics of rat liver spermidine/spermine N1-acetyltransferase.
The substrate specificity and kinetic mechanism of spermidine N1-acetyltransferase from rat liver was investigated using a highly purified (18 000-fold) preparation from the livers of rats in which...
Studies of the acetyl-CoA-binding site of rat liver spermidine/spermine N1-acetyltransferase.
Della Ragione, F, Erwin, B G, Pegg, A E
Rat liver spermidine/spermine N1-acetyltransferase was found to be strongly inhibited by the dyes Cibacron F3GA, Coomassie Brilliant Blue and Congo Red. Inhibition was competitive with respect to...
A radioimmunoassay for ornithine decarboxylase was used to study the regulation of this enzyme in rat liver. The antiserum used reacts with ornithine decarboxylase from mouse, human or rat cells. Rat...
Induction of spermidine/spermine N1-acetyltransferase in rat tissues by polyamines.
Treatment of rats with spermidine, spermine or sym-norspermidine led to a substantial induction of spermidine/spermine N1-acetyltransferase activity in liver, kidney and lung. The increase in this...
Della Ragione, F, Porcelli, M, Cartenì-Farina, M, Zappia, V, Pegg, A E
S-Adenosylhomocysteine/5'-methylthioadenosine nucleosidase (EC 3.2.2.9) was purified to homogeneity from Escherichia coli to a final specific activity of 373 mumol of 5'-methylthioadenosine...
Studies of mammalian ornithine decarboxylase using a monoclonal antibody.
Pegg, A E, Seely, J E, Persson, L, Herlyn, M, Ponsell, K, O'Brien, T G
A monoclonal antibody of the immunoglobulin M class was produced against mouse kidney ornithine decarboxylase. Screening for the antibody was carried out using...
The effects of a number of nucleosides related to 5'-methylthioadenosine on the activities of S-adenosylhomocysteine hydrolase, 5'-methylthioadenosine phosphorylase, spermidine synthase and spermine...
1. The induction of ornithine decarboxylase activity in mouse 3T3 fibroblasts or an SV-40 transformed 3T3 cell line by serum was prevented by addition of the naturally occurring polyamines putrescine...
Pegg, A E, Perry, W, Bennett, R A
1. The activity of an enzyme catalysing the loss of O6-methylguanine from methylated DNA was increasing during liver regeneration after partial hepatectomy. Activity was increased 3-fold by 24h and...
Specificity of mammalian spermidine synthase and spermine synthase.
Pegg, A E, Shuttleworth, K, Hibasami, H
1. The specificity of rat prostatic spermidine synthase and spermine synthase with respect to the amine acceptor of the propylamine group was studied. 2. Spermidine synthase could use cadaverine...
1. Administration of spermidine or sym-norspermidine decreased the activity of AdoMet (S-adenosylmethionine) decarboxylase in extracts prepared from rat liver, Kidney, psoas, diaphragm, soleus and...
1. Polyamine concentrations were decreased in rats fed on a diet deficient in vitamin B-6. 2. Ornithine decarboxylase activity was decreased by vitamin B-6 deficiency when assayed in tissue extracts...
Studies of the ethylation of rat liver transfer ribonucleic acid after administration of l-ethionine
1. The ethylated nucleosides present in tRNA isolated from the livers of rats treated with 0.5g of l-ethionine/kg body wt. were investigated. Evidence that this tRNA contained N2-ethylguanine,...
Evidence for ethylation of rat liver deoxyribonucleic acid after administration of ethionine
Swann, P. F., Pegg, A. E., Hawks, A., Farber, E., Magee, P. N.
1. Administration of a large dose (500mg/kg body wt.) of 3H-labelled l-ethionine to rats resulted in the incorporation of a small amount of radioactivity into the liver DNA. Considerable evidence...
Inhibition of spermidine formation in rat liver and kidney by methylglyoxal bis(guanylhydrazone)
The effect of methylglyoxal bis(guanylhydrazone), a substance known to inhibit putrescine-dependent S-adenosyl-l-methionine decarboxylase, on polyamine metabolism in liver and kidney was...
Mangan, F. R., Pegg, A. E., Mainwaring, W. I. P.
1. A comparison was made of the binding of 5α-dihydrotestosterone (17β-hydroxy-5α-androstan-3-one) and cyclic AMP in the rat prostate gland. Distinct binding mechanisms exist for these compounds,...
Pegg, A. E., Lockwood, D. H., Williams-Ashman, H. G.
1. Castration of adult rats resulted in marked decreases in the amounts of putrescine, spermidine and spermine in the ventral prostate gland. Spermidine concentrations decline rapidly over the first...
Rapid and convenient method for the assay of aminopropyltransferases.
A new method for the assay of aminopropyltransferase activity is described. The method measures the formation of [methyl-14C]methylthioadenosine from decarboxylated S-adenosyl[methyl-14C]methionine...
Effects of aliphatic diamines on rat liver ornithine decarboxylase activity.
Pegg, A E, Conover, C, Wrona, A
Rat liver ornithine decarboxylase activity was decreased by administration of putrescine (1,4-diaminobutane) or other diamines, including 1,3-diaminopropane, 1,5-diaminopentane and 1,6-diaminohexane....
Phosphate-stimulated breakdown of 5′-methylthioadenosine by rat ventral prostate
Pegg, A. E., Williams-Ashman, H. G.
A soluble enzyme preparation catalysing the release of adenine from 5′-methylthioadenosine was purified some 30-fold from extracts of the rat ventral prostate. This reaction was completely...
Biosynthesis of putrescine in the prostate gland of the rat
Pegg, A. E., Williams-Ashman, H. G.
In the rat ventral prostate gland the biosynthesis of putrescine, a precursor of spermidine and spermine, is shown to occur by the direct decarboxylation of l-ornithine. Some properties of a soluble...
Structure and critical residues at the active site of spermidine/spermine-N1-acetyltransferase.
Coleman, C S, Huang, H, Pegg, A E
Spermidine/spermine-N1-acetyltransferase (SSAT) is a key enzyme in the degradation of polyamines. Alanine-scanning mutagenesis of all eight arginine residues was used to investigate the arginine...
Engel, N, Olmo, M T, Coleman, C S, Medina, M A, Pegg, A E, Sánchez-Jiménez, F
Common protein motifs between histidine decarboxylase (HDC) and ornithine decarboxylase (ODC) were detected by computational analysis. Mutants were generated and expressed in vitro. In both enzymes,...
Nishikawa, Y, Kar, S, Wiest, L, Pegg, A E, Carr, B I
We screened genes responsive to transforming growth factor-beta (TGF-beta 1) protein in a human hepatoma cell line (Hep3B) using a PCR-mediated differential display technique, in order to investigate...
Rapid induction of apoptosis by deregulated uptake of polyamine analogues.
Treatment of Chinese hamster ovary cells with alpha-difluoromethylornithine for 3 days, followed by exposure to cycloheximide, led to an unregulated, rapid and massive accumulation of polyamine...
Kanugula, S, Goodtzova, K, Pegg, A E
Human O6-alkylguanine-DNA alkyl transferase (hAGT) is a DNA repair protein that protects cells from alkylation damage by transferring an alkyl group from the O6-position of guanine to a cysteine...
The DNA repair protein, O(6)-alkylguanine-DNA alkyltransferase (AGT), is inactivated by reaction with the pseudosubstrate, O(6)-benzylguanine (BG). This inactivation sensitizes tumour cells to...
Xu-Welliver, M, Kanugula, S, Loktionova, N A, Crone, T M, Pegg, A E
The role of lysine(165) in the activity of the DNA repair protein, O(6)-alkylguanine-DNA alkyltransferase (AGT), and the ability of AGT to react with the pseudosubstrate inhibitor, O(6)-benzylguanine...
Mackintosh, C A, Feith, D J, Shantz, L M, Pegg, A E
Two lines of transgenic mice were produced with constitutive expression of antizyme-1 in the heart, driven from the cardiac alpha-myosin heavy chain promoter. The use of engineered antizyme cDNA in...
Mutant Gy male mice, which have previously been described as having disruption of the phosphate-regulating Phex gene and a spermine synthase gene [Meyer, Henley, Meyer, Morgan, McDonald, Mills and...
Effect of polyamine depletion on caspase activation: a study with spermine synthase-deficient cells.
Stefanelli, C, Pignatti, C, Tantini, B, Fattori, M, Stanic, I, Mackintosh, C A, ...
Activation of the caspase proteases represents a central point in apoptosis. The requirement for spermine for the processes leading to caspase activation has been studied in transformed embryonic...
Shantz, L M, Feith, D J, Pegg, A E
These studies were designed to determine the consequences of constitutive overexpression of ornithine decarboxylase (ODC) in the heart. Induction of ODC is known to occur in response to agents that...
Spermidine/spermine N(1)-acetyltransferase (SSAT), a key enzyme in mammalian polyamine catabolism, undergoes rapid turnover (half-life approx. 30 min) and is highly inducible in response to polyamine...
Lu, L, Stanley, B A, Pegg, A E
The importance of certain amino acid residues in mammalian ornithine decarboxylase activity and degradation was studied by site-specific mutagenesis. Changes were made to the mouse ornithine...
Pegg, A E, Dolan, M E, Scicchitano, D, Morimoto, K
O6-Methylguanine in DNA is repaired by the action of a protein termed O6-alkylguanine-DNA alkyltransferase (AT) which transfers the methyl group to a cysteine residue in its own sequence. Since the...
Dolan, M E, Moschel, R C, Pegg, A E
O6-Alkylguanine-DNA alkyltransferase was rapidly and irreversibly inactivated by exposure to O6-benzylguanine or the p-chlorobenzyl and p-methylbenzyl analogues. This inactivation was much more rapid...
Repair of O-alkylpyrimidines in mammalian cells: a present consensus.
Brent, T P, Dolan, M E, Fraenkel-Conrat, H, Hall, J, Karran, P, Laval, L, ...
Enzymatic repair of the O-alkylpyrimidines (O2- and O4-alkylthymine, O2-alkylcytosine) and alkyl phosphotriesters has been studied in Escherichia coli, and the two proteins involved, a glycosylase...
Enzymatic release of 7-methylguanine from methylated DNA by rodent liver extracts.
Rat and hamster liver extracts were found to contain DNA glycosylases capable of removing 3-methyladenine and 7-methylguanine from methylated DNA. The activity of 7-methylguanine-DNA glycosylase was...
Removal of O6-methylguanine from DNA by human liver fractions.
Pegg, A E, Roberfroid, M, Von Bahr, C, Foote, R S, Mitra, S, Bresil, H, ...
In in vitro assays using methylated DNAs as substrates, human liver fractions were shown to be able to catalyze the removal of O6-methylguanine. The amount of removal was proportional to the amount...
Swenberg, J A, Bedell, M A, Billings, K C, Umbenhauer, D R, Pegg, A E
The activity of the alkyl acceptor protein (AAP) responsible for repair of DNA containing the promutagenic lesion O6-alkylguanine was determined in hepatocytes and nonparenchymal cells (NPC) obtained...
Pegg, A E, Pakala, R, Bergeron, R J
Treatment of Chinese-hamster ovary (CHO) cells