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M A Desiderio

Publications and source records attributed to M A Desiderio.

At least 37 records · Page 2Linked to original sources
PubMed1993

Cytosolic and nuclear spermidine acetyltransferases in growing NIH 3T3 fibroblasts stimulated with serum or polyamines: relationship to polyamine-biosynthetic decarboxylases and histone acetyltransferase.

The expression (mRNA level of enzymic activity) of cytosolic and nuclear spermidine acetyltransferases was studied in NIH 3T3 fibroblasts, either (1) serum-starved and stimulated to grow by serum refeeding, or (2) treated with inhibitors of ornithine decarboxylase (ODC) (MDL 72.175) and S-adenosylmethionine decarboxylase (AdoMetDC) (MDL 73.811) and stimulated to grow by spermidine. Expression of the known growth-regulated genes for ODC, AdoMetDC and histone acetyltransferase was also examined. The mRNA for spermidine/spermine N1-acetyltransferase (SAT) accumulated after serum refeeding (between 6 and 16 h) and even more after spermidine addition (16 h). Histone acetyltransferase activity increased after both growth stimuli, whereas spermidine N8-acetyltransferase activity remained unchanged. After serum stimulation, the ODC mRNA level and activity rose between 6 and 16 h, whereas AdoMetDC mRNA accumulation occurred later (16 h) than the increase in enzyme activity (6 h). Stimulation of ODC and AdoMetDC activities was suppressed by the inhibitors added alone or in combination with spermidine, whereas mRNA accumulation was down-regulated by spermidine. These results indicate that the expression of SAT was growth-controlled and that SAT mRNA level was regulated by polyamines.

3T3 Cells↗
PubMed1992

Opposite responses of nuclear spermidine N8-acetyltransferase and histone acetyltransferase activities to regenerative stimuli in rat liver.

Experiments performed in different models of hepatic regeneration at the time of maximal DNA synthesis, determined by thymidine kinase activity assay, demonstrated that spermidine N8-acetyltransferase activity increased 48 hr after CCl4 administration (2-fold), 72 hr after CCl4 plus phenobarbital (3-fold) and 24 hr after partial hepatectomy (4.5-fold). On the contrary, at these times histone acetyltransferase activity diminished (approximately twofold) and was unchanged compared with control values in the liver of hepatotoxin-treated and hepatectomized rats, respectively. Histone acetylation was, however, enhanced 1.5-fold before the onset of DNA replication (14 hr), and 3.4-fold after the peak of DNA synthesis (32 hr) in the liver of hepatectomized rats. alpha-Difluoromethylornithine, a specific and irreversible inhibitor of ornithine decarboxylase that was administered to hepatectomized rats, blocked polyamine synthesis, thymidine kinase activity and consequently liver regeneration 24 hr after the surgery. In those conditions, spermidine N8-acetyltransferase activity was decreased approximately twofold, whereas histone acetyltransferase activity was elevated approximately twofold. All these effects were reversed by putrescine coadministration. Altogether, these findings showed that nuclear spermidine N8-acetyltransferase and histone acetyltransferase activities were regulated in opposite ways during the processes associated with liver regeneration. Moreover, they suggested that the polyamines themselves might have a direct or indirect role in this regulation.

Acetyltransferases↗
PubMed1992

Spermidine nuclear acetylation in rat hepatocytes and in logarithmically growing rat hepatoma cells: comparison with histone acetylation.

Spermidine acetylation has been studied in nuclear homogenates and in entire nuclei from rat hepatocytes and rat hepatoma tissue culture (HTC) cells, isolated at different stages of logarithmic growth, and compared to histone acetylation. Under all experimental conditions, N8-acetylspermidine was the predominant product of the reaction (90%). Unlike histone, spermidine acetylation in HTC cell and hepatocyte entire nuclei was almost absent or strikingly reduced relative to acetylation using nuclear homogenates as the enzyme sources. This was due to the lack of a free minor pool of spermidine, most likely lost during the purification of entire nuclei. Thus, preincubation of intact nuclei in the presence of spermidine restored activities to values observed using nuclear sonicates. Spermidine acetylation in HTC cell nuclei fluctuated moderately during cell growth, being stimulated immediately after initiation of proliferation and decreasing progressively as cultures reached high cell density. This pattern corroborated that of N8-acetylspermidine intracellular accumulation induced by culturing cells in the presence of 1 mM 7-amino-2-heptanone, a competitive inhibitor of N8-acetylspermidine deacetylase. Histone acetylation during HTC cell growth was not markedly different qualitatively from that of spermidine. Moreover, spermidine and histone acetylations in hepatocyte nuclei were of the same order of magnitude as those seen in rat hepatoma cell nuclei. Finally, inhibition of deacetylation of N8-acetylspermidine had no apparent deleterious effects on cell and growth. It remains to be determined whether the acetylation step is of higher physiological importance, in particular, and as discussed in nuclear spermidine turnover.

Acetylation↗
PubMed1990

Effect of adrenergic and Ca2+ antagonists on increased ornithine decarboxylase expression in regenerating rat liver.

Partial hepatectomy (PH) (70% resection) causes within 4 hr an accumulation of ornithine decarboxylase (EC 4.1.1.17, ODC) mRNAs concomitant with an increase in ODC activity, maximum values being observed at 8 and 16 hr, respectively. In the early hours of hepatic regeneration, enhancement of transcriptional-rate of ODC gene, demonstrated by nuclear run-on analysis, can account for the accumulation of ODC mRNAs. The involvement of catecholamines in these processes is demonstrated by using prazosin and propranolol, specific antagonists of alpha 1 and beta adrenoceptors, respectively. Prazosin reduces almost completely the rise of ODC activity at 4 hr, without affecting mRNA levels. At 16 hr, enzyme activity and mRNAs increase, however, over the values observed in regenerating liver of prazosin-untreated animals. These findings suggest that alpha 1-receptor activation triggers positive control signals for ODC gene expression at the early time of liver regeneration and, on the contrary, negative signals at later times by mainly post-transcriptional and transcriptional mechanisms, respectively. Propranolol reduces similarly the initial 4 hr-rise of ODC activity. These results indicate that activation of both alpha 1- and beta-adrenoceptors causes the large increase in ODC activity. Pharmacological manipulation of intracellular Ca2+ levels by verapamil, a Ca2(+)-channel blocker, or neomycin, an inhibitor of Ca2+ release from endogenous stores, diminishes ODC activity at 4 and 16 hr after PH. ODC mRNA levels, which are not modified at 4 hr, increase over the values of partially hepatectomized rat liver at 16 hr. Trifluoperazine inhibits both ODC activity and mRNA accumulation at the times studied. As a working hypothesis it is proposed that Ca2(+)-mediated processes induced by catecholamines are involved in ODC gene expression during the prereplicative phase of liver regeneration.

Adrenergic alpha-Antagonists↗
PubMed1990

Diamine oxidase activity in a model of multistep hepatocarcinogenesis.

Treatment of rats with a complete hepatocarcinogenic regimen (diethylnitrosamine, 2-acetylaminofluorene and partial hepatectomy) produced a prolonged stimulation of diamine oxidase activity in liver, which showed early and persistent preneoplastic nodules. Diethylnitrosamine or partial hepatectomy tested separately caused a transient increase in enzyme activity. Early nodules, which were positive for gamma-glutamyltransferase activity, and hepatomas showed diamine oxidase activity of approximately 5- and 13-fold that of control liver, respectively. These results indicate an activation of terminal catabolism of polyamines in preneoplastic nodules and in hepatomas.

2-Acetylaminofluorene↗
PubMed1990

Estrogenic regulation of diamine oxidase activity in rat uterus.

Diamine oxidase activity was studied in female rat tissues during the estrous cycle and after 17 beta-estradiol administration. During the estrous cycle, uterine and hepatic enzyme activities were highest at proestrus and lowest at estrus, when estrogen plasma levels are known to be respectively high and low. The administration of 17 beta-estradiol to ovariectomized rats caused a rapid and prolonged increase in enzyme activity in uterus and only a transient increase in the liver. Such increases were prevented by cycloheximide and by actinomycin D administration. No changes were observed in renal enzyme activity during estrus or after hormone treatment. Our data suggest that estrogens regulate diamine oxidase activity in rat uterus by a mechanism of enzyme induction.

Amine Oxidase (Copper-Containing)↗
PubMed1988

Effect of rate of rise of blood alcohol on outcome of cardiac injury.

In our initial study in anesthetized dogs, single 7-minute intravenous alcohol doses caused a 67% mortality with cardiac impact at 65 mg% blood alcohol. In the next study, equally spaced oral doses over 40 minutes resulted in only a 17% mortality at an equivalent blood alcohol level and injury severity. Intravenous doses of a 50% ethanol/isotonic saline solution were given at equally spaced intervals over 40 minutes to generate peak blood alcohol levels and rates of rise equivalent to the oral study. Impacts with a velocity of 10 m/s and a contact compression of 5 cm were delivered to 85-90% of the right pericardial surface. The 25% mortality from alcohol and trauma was comparable to that observed in the oral study. These results attest to the importance of the rate of alcohol administration over the route on the outcome of cardiac injury.

Animals↗
PubMed1988

Polyamines, ornithine decarboxylase, and diamine oxidase in the substantia nigra and striatum of the male rat after hemitransection.

Partial hemitransection at the mesodiencephalic junction in the rat increased striatal and nigral putrescine concentrations on the lesioned side for at least 168 h, with maximal increases between 24 and 48 h. Spermidine and spermine levels declined at 24 h in the striatum, rising above control values at 48 h and further at 168 h. In the substantia nigra, they remained unchanged for the first 48 h and then increased by 168 h. Cadaverine in the striatum also increased at 48 h. On the intact side putrescine increased but to a much lesser extent (at 48 h in the striatum and at 24 and 48 h in the substantia nigra). Ornithine decarboxylase and diamine oxidase activities showed maximal increases at 24 h in the striatum of the lesioned side, whereas in the substantia nigra ornithine decarboxylase attained a very high value as early as 4 h after the operation and diamine oxidase activity peaked at 48 h. The enzyme activities returned toward the basal values at 168 h. On the intact side, ornithine decarboxylase showed a small increase starting at 4 h and diamine oxidase was enhanced at 48 h. These results indicate that the stimulation of biosynthetic and degradative enzymes of polyamine metabolism accompanied by marked and prolonged increases in putrescine may be essential events in the early phases of neuronal response to mechanical injury in the CNS.

Amine Oxidase (Copper-Containing)↗
PubMed1987

Polyamines and diamine oxidase activity in maternal, embryonal, and fetal tissues of rat after chronic ethanol consumption.

The effects of maternal ethanol consumption for 4 weeks before and throughout gestation on polyamine content and diamine oxidase activity of maternal, embryonal and fetal tissues are reported. At the 12th day of pregnancy, a decrease of putrescine in the liver of the mother and marked increases in putrescine, cadaverine and spermidine in embryos were observed. At day 18, putrescine and cadaverine diminished in maternal liver and placenta, and no changes in amine content in fetal liver and brain were found. At day 12, diamine oxidase activity increased in maternal liver and placenta, whereas it greatly diminished in embryos. At day 18, enzyme activity decreased in maternal liver, placenta, fetal liver and brain. These results indicate that chronic ethanol ingestion induces alterations in polyamine concentrations and metabolism in growing and developing tissues during pregnancy that might contribute to the adverse effect of ethanol on conceptual development.

Amine Oxidase (Copper-Containing)↗
PubMed1987

Effect of acute ethanol administration on diamine oxidase activity in maternal, embryonal and fetal tissues.

Pregnant rats were acutely treated with ethanol to study the influence of this drug on diamine oxidase activity of maternal, embryonal, and fetal tissues. When ethanol was given on day 12 of gestation, enzyme activity was unmodified in placenta and embryo, whereas it was reduced by 38 and 31%, respectively, in maternal liver and plasma at 3 h. When ethanol was given on day 18 of gestation, diamine oxidase activity diminished in maternal liver, plasma and placenta by about 35-40% at 6 h. Moreover, in the fetus ethanol caused a 35% diminution of enzyme activity in liver at 6 h and a 45% stimulation in brain at 3 h, and of about 65% at 6-12 h. These data may be of interest in view of the physiological role of diamine oxidase in the oxidation of the large amounts of amines produced during pregnancy.

Amine Oxidase (Copper-Containing)↗
PubMed1987

Effects of acute, oral ethanol on cardiovascular performance before and after experimental blunt cardiac trauma.

Acute changes in hemodynamic and electrophysiologic indices were measured following blunt cardiac trauma, oral ethanol, and a combination of both in dogs. Impacts with a velocity of 10 m/sec and a contact compression of 5 cm were delivered to most of the pericardium. Transient arrhythmias in impacted animals resulted in significant reductions in all hemodynamic responses at 15 minutes post-impact. Intragastric doses of 50% ethanol/distilled water yielded average blood alcohol concentrations of 60 +/- 10 mg%, 120 +/- 20 mg%, and 180 +/- 15 mg%. Alcohol effected significant reductions in dp/dt and cardiac index and elevations in total peripheral resistance during treatment. Alcohol and trauma resulted in per cent mortalities of 17, 50, and 71% for each such group primarily from electrical-mechanical dissociation. Surviving animals experienced significant declines in dp/dt, cardiac index, and mean aortic pressure at 15 minutes post-impact. Mean aortic pressure remained depressed while dp/dt, cardiac index, and total peripheral resistance returned to control values.

Administration, Oral↗
PubMed1987

Ethanol and polyamine metabolism in adult and fetal tissues: possible implication in fetus damage.

The influence of ethanol treatment on various enzymes involved in the metabolism of polyamines, substances implicated in cell physiology, growth and differentiation, is reviewed. In particular, we studied the effect of acute in utero ethanol exposure on fetal liver diamine oxidase, the enzyme involved in the oxidative deamination of biogenic amines as well as in the terminal catabolism of polyamines. Ethanol, in contrast to that previously observed in adult rat liver, caused in fetal liver a significant diminution in diamine oxidase activity, which appeared reversible and was not dose-dependent with 2 or 4 g/kg body weight. These findings and the possible implication of altered polyamine metabolism in the pathogenesis of fetal alcohol syndrome are discussed.

Adult↗
PubMed1986

Response of tissue diamine oxidase activity to polyamine administration.

The administration to rats of putrescine (750 mumol/kg body wt.) caused in liver, kidney and heart an increase in putrescine at 1 h and in diamine oxidase (EC 1.4.3.6) activity within 3-6 h. An increase in spermidine was observed at 9 h in liver and at 6 h in kidney, whereas in heart there was no change. The increase in diamine oxidase activity by exogenous putrescine was prevented by the administration of actinomycin D and cycloheximide, suggesting that syntheses of mRNA and protein are involved. Equimolar doses of 1,3-diaminopropane, 1,5-diaminopentane and monoacetylputrescine stimulated, similarly to putrescine, hepatic, renal and cardiac diamine oxidase activity. After the injection of a non-toxic dose of spermidine (750 mumol/kg body wt.), the increase in diamine oxidase activity occurred at 9 h in all the tissues studied, when a substantial putrescine formation from spermidine occurred. sym-Norspermidine, which is unable to form putrescine, did not cause an increase in enzyme activity. The possibility that the tissue contents of putrescine might regulate diamine oxidase activity is discussed.

Amine Oxidase (Copper-Containing)↗
PubMed1986

The potentiation of the response to blunt cardiac trauma by ethanol in dogs.

Acute changes in mechanical performance and electrical activity were followed after blunt cardiac trauma, ethanol infusion, and ethanol infusion and blunt cardiac trauma in 21 anesthetized dogs. Impact was delivered to most of the pericardium with an impact velocity of 10 m/sec and a contact compression of 5 cm. Impact alone caused transient arrhythmias and significant reductions in all hemodynamic parameters with ultimate recovery of rhythm and cardiac performance within 60 minutes after impact. Intravenous infusion of ethanol (average blood alcohol concentration, 65 +/- 1 mg %), resulted in no significant alterations in either mechanical performance or electrical activity but, when combined with trauma, caused a mortality rate of 67%. All animals died from excitation-contraction decoupling; a dissociation of electrical from mechanical activity such that an electrical event does not elicit a mechanical event strong enough to sustain life. It is concluded that even low blood alcohol concentrations can significantly reduce cardiac performance in the presence of otherwise nonfatal cardiac injury.

Animals↗
PubMed1985

Regulation of diamine oxidase expression by beta 2-adrenoceptors in normal and hypertrophic rat kidney.

The administration of preferential adrenergic receptor antagonists to uninephrectomized rats revealed the beta 2-adrenergic mediation in diamine oxidase activity increase that occurs in the remaining kidney undergoing compensatory hypertrophy. In fact, beta 1, beta 2- or beta 2, but not alpha 1-, alpha 2-, or beta 1-receptor-blocking agents prevented this enzyme enhancement. Further studies with adrenoceptor agonists, such as epinephrine (alpha 1, alpha 2, beta 1, beta 2), isoproterenol (beta 1, beta 2) or terbutaline (beta 2) showed that also in normal rat kidney diamine oxidase activity is under the control of catecholamine-beta 2-receptors through a mechanism that involves new synthesis of mRNA and protein. Theophylline, an inhibitor of phosphodiesterase, or forskolin, an activator of adenyl cyclase, increased diamine oxidase activity as does epinephrine or nephrectomy. Thus, catecholamine-triggered beta 2-receptors coupled to adenyl cyclase are involved in the regulation of diamine oxidase activity in normal and hypertrophic rat kidney.

Adrenergic Agonists↗
PubMed1984

Stimulation of hepatic and renal diamine oxidase activity after acute ethanol administration.

The effect of a single administration of ethanol (2 g/kg body weight) on hepatic and renal diamine oxidase activity was studied in fasted rats. Diamine oxidase activity significantly increased in liver and kidney 6 h after ethanol intubation. Pyrazole (an inhibitor of alcohol dehydrogenase), cycloheximide or actinomycin D (inhibitors of macromolecular syntheses), as well as prior adrenalectomy, prevented the ethanol-induced stimulation of diamine oxidase in the liver, but not in the kidney. The results demonstrated that the enhancement of diamine oxidase activity in the liver was due to an enzyme induction mediated by alcohol metabolism as well as by adrenals. In contrast, the stimulation of diamine oxidase activity in the kidney did not depend on synthesis of new enzyme molecules and was not mediated by ethanol metabolism or adrenal hormones.

Amine Oxidase (Copper-Containing)↗