scholarly journals Polyamine metabolism in liver of young rats

1978 ◽  
Vol 174 (3) ◽  
pp. 727-732 ◽  
Author(s):  
M E Brosnan ◽  
G W Symonds ◽  
D E Hall ◽  
D L Symonds

Rat liver undergoes a phase of rapid growth during weaning. We followed the changes in polyamine metabolism occurring during this period of natural growth, and compared them with changes in DNA and RNA accumulation. There was a 2.5-fold increase in the number of cells per liver between suckling (18–19 days old) and weaning (30–32 days old) rats. Ornithine decarboxylase activity increased from the low value in 18-day-old rat pups and remained significantly higher (approx. 5–10-fold) than that in adult rats from day 21 to day 34. Putrescine-dependent S-adenosylmethionine decarboxylase activity was slightly but significantly increased during most of this period. Spermidine and RNA concentrations fluctuated in concert, whereas spermine content per cell doubled during the period from day 23 to day 30.

1982 ◽  
Vol 202 (1) ◽  
pp. 175-181 ◽  
Author(s):  
C Danzin ◽  
N Claverie ◽  
J Wagner ◽  
J Grove ◽  
J Koch-Weser

2-Difluoromethylornithine (DFMO), an enzyme-activated irreversible inhibitor of ornithine decarboxylase, causes marked changes in the polyamine metabolism of ventral prostate when given to adult rats in drinking water (20 g/l) for 3 consecutive days. A 90% inhibition of ornithine decarboxylase activity is accompanied by approx. 80% decreases of the concentrations of putrescine and spermidine and by a 36% decrease in spermine. Concomitantly, S-adenosylmethionine decarboxylase activity increases 7-fold and the concentration of decarboxylated S-adenosylmethionine 450-fold. When DFMO is given to immature rats for 12 consecutive days the above described changes are accompanied by a marked reduction in the age-dependent increases of the wet weight and RNA and DNA contents of the ventral prostate. In adult rats DFMO decreases the weight and RNA content of the ventral prostate within 4 days by 32% and 24% respectively and maintains them constant for the next 19 days. After 23 days of treatment, the prostatic weight is 46% of that of control animals of the same age, whereas the weights of other organs are only slightly decreased. Cytological studies carried out at this time show that DFMO reduces the size of both prostatic acini and the epithelial cells lining the acini.


1981 ◽  
Vol 196 (2) ◽  
pp. 603-610 ◽  
Author(s):  
D Hopkins ◽  
K L Manchester

Concentrations of spermidine, spermine and putrescine have been measured in rat diaphragm muscle after unilateral nerve section. The concentration of putrescine increased approx. 10-fold 2 days after nerve section, that of spermidine about 3-fold by day 3, whereas an increase in the concentration of spermine was only observed after 7-10 days. It was not possible to show enhanced uptake of either exogenous putrescine or spermidine by the isolated tissue during the hypertrophy. Consistent with the accumulation of putrescine, activity of ornithine decarboxylase increased within 1 day of nerve section, was maximally elevated by the second day and then declined. Synthesis of spermidine from [14C]putrescine and either methionine or S-adenosylmethionine bt diaphragm cytosol rose within 1 day of nerve section, but by day 3 had returned to normal or below normal values. Activity of adenosylmethionine decarboxylase similarly increased within 1 day of nerve section, but by day 3 had declined to below normal values. Activity of methionine adenosyltransferase was elevated throughout the period studied. The concentration of S-adenosylmethionine was likewise enhanced during hypertrophy. Administration of methylglyoxal bis(guanylhydrazone) produced a marked increase in adenosylmethionine decarboxylase activity and a large increase in putrescine concentration, but did not prevent the rise in spermidine concentration produced by denervation. Possible regulatory mechanisms of polyamine metabolism consistent with the observations are discussed.


2011 ◽  
pp. 961-969 ◽  
Author(s):  
J. TCHEKALAROVA ◽  
H. KUBOVÁ ◽  
P. MAREŠ

Repeated postnatal caffeine treatment of rat pups led to transient developmental changes in cortical epileptic afterdischarges. To know if physiological cortical functions are also affected transcallosal evoked potentials were studied. Rat pups of the Wistar strain were injected daily with caffeine (10 or 20 mg/kg s.c.) from postnatal day (P) 7 to P11, control siblings received saline. Cortical interhemispheric responses were tested at P12, 18, 25 and in young adult rats. Amplitude of initial monosynaptic components was evaluated in averaged responses. Single pulses as well as paired and frequency (five pulses) stimulations were used. Developmental rules – highest amplitude of responses in 25-day-old rats, potentiation with paired and frequency stimulation present since P18 – were confirmed. Caffeine-treated rats exhibited transient changes: single responses were augmented in P25 if high stimulation intensity was used, paired-pulse and frequency responses were higher in experimental than in control animals at P12, the opposite change was observed in 18- and more markedly in 25-day-old rats. No significant changes were found in adult animals, monosynaptic transcallosal responses represent a simple and robust system. The developmental profile of described changes did not exactly correspond to changes in epileptic afterdischarges supporting the possibility that afterdischarges did not arise from early monosynaptic components of responses. In spite of transient nature of changes they can reflect delayed or more probably modified brain development.


1981 ◽  
Vol 29 (10) ◽  
pp. 1189-1195 ◽  
Author(s):  
T Tanaka ◽  
E W Gresik ◽  
T Barka

An antiserum against purified rat parotid amylase was used to localize the protein in parotid glands of developing and adult rats. The unlabeled antibody peroxidase-antiperoxidase method and the protein A-gold colloid technique were used at the light and electron microscope levels, respectively. Immunoreactive amylase was detected in a few scattered cells in the glands of 2-day-old rats. During the following days the number of cells stained immunocytochemically for amylase increased rapidly; at 15 days of age all acinar cells revealed amylase, but the intensity of immunostaining varied from cell to cell. Electron microscopically, amylase was localized in the secretory granules, and by using a more concentrated antiserum, in the rough endoplasmic reticulum and Golgi complex. At early stages of development the acinar cells contained fewer and smaller secretory granules than in adult animals; the gold particles indicative of amylase were randomly distributed over the secretory granules. In the glands of adult rats, amylase was distributed inhomogeneously within the secretory granules. In the majority of secretory granules gold colloid particles were located over the electron-dense portions of the granules. However, secretory granules in which an amylase-rich shell surrounded an amylase-poor or amylase-negative "core" were not infrequent.


1981 ◽  
Vol 61 (4) ◽  
pp. 1005-1012 ◽  
Author(s):  
T. K. SMITH

Experiments were conducted to determine the effects of factorial combinations of dietary ornithine and methionine on chick growth, carcass composition, and the regulatory enzymes of polyamine synthesis. Week-old leghorn cockerel chicks were fed 12 soy protein-based semipurified diets containing 0.00, 0.50, 0.85 or 1.25% ornithine plus 0.55, 0.75 or 1.00% methionine for 2 wk. Weight gains were depressed as dietary methionine increased but only when ornithine was fed at less than 0.85%. Ornithine supplements depressed growth regardless of methionine levels. Carcass protein decreased with supplemental ornithine when methionine was fed at 0.55% but not at higher levels. Methionine supplements decreased carcass protein only in the absence of ornithine. Feeding 0.85% ornithine plus 0.55% methionine resulted in increased activity of S-adenosylmethionine decarboxylase in heart, pancreas, and muscle when compared to the control diet containing 0.00% ornithine plus 0.55% methionine. Dietary ornithine supplements lowered ornithine decarboxylase activities in heart, pancreas, and liver regardless of methionine level. It can be concluded that there is a nutritional interrelationship between ornithine and methionine as indicated by their cumulative effects on growth, carcass composition, and S-adenosylmethionine decarboxylase activity.


2011 ◽  
Vol 438 (2) ◽  
pp. 229-244 ◽  
Author(s):  
Lyn-Marie Birkholtz ◽  
Marni Williams ◽  
Jandeli Niemand ◽  
Abraham I. Louw ◽  
Lo Persson ◽  
...  

New drugs are urgently needed for the treatment of tropical and subtropical parasitic diseases, such as African sleeping sickness, Chagas' disease, leishmaniasis and malaria. Enzymes in polyamine biosynthesis and thiol metabolism, as well as polyamine transporters, are potential drug targets within these organisms. In the present review, the current knowledge of unique properties of polyamine metabolism in these parasites is outlined. These properties include prozyme regulation of AdoMetDC (S-adenosylmethionine decarboxylase) activity in trypanosomatids, co-expression of ODC (ornithine decarboxylase) and AdoMetDC activities in a single protein in plasmodia, and formation of trypanothione, a unique compound linking polyamine and thiol metabolism in trypanosomatids. Particularly interesting features within polyamine metabolism in these parasites are highlighted for their potential in selective therapeutic strategies.


1980 ◽  
Vol 188 (2) ◽  
pp. 491-501 ◽  
Author(s):  
L Alhonen-Hongisto ◽  
H Pösö ◽  
J Jänne

The anti-proliferative effects of 1,1′-[(methylethanediylidene)dinitrilo]diguanidine [methylglyoxal bis(guanylhydrazone)] and 1,1′-[(metHYLETHANEDIYLIDENE)dinitrilo]bis-(3-aminoguaNIDINE) HAVE BEEN STUDIED IN Ehrlich ascites carcinoma cells grown in suspension cultures. Both compounds are potent inhibitors of S-adenosyl-L-methionine decarboxylase from the tumour cells. In the presence of putrescine (but not in its absence), the inhibition produced by 1,1′-[methylethanediylidene)dinitrilo]bis-(3-aminoguanadine) was apparently irreversible, as judged by persistent depression of the enzyme activity even after extensive dialysis. The two compounds produced similar increases in adenosylmethionine decarboxylase activity, which resulted from a striking stabilization of the enzyme in cells grown in the presence of the drugs. The inhibitory effect of the two diguanidine derivatives on the synthesis of DNA and protein became evident after an exposure of 4–8 h. At that time, the only change seen in tumour polyamines in cells grown in the presence of the inhibitors was an increase in cellular putrescine. To find out whether the compounds initially interfered with the energy production of the tumour cells, the cultures were grown in the presence of uniformly labelled glucose, and the formation of lactate, as well as the oxidation of the sugar into CO2, were measured. The activation of glycolysis upon dilution of the tumour cells with fresh medium and the subsequent formation of labelled CO2 were siliar in control cells and in cells exposed to methylglyoxal bis(buanylhydrazone), 1,1′-[(methylethanediylidene)dinitrilo]bis-(3-aminoguanidine) or diaminopropanol. Only a marginal decrease in the cellular content of ATP was found in cells exposed to the inhibitors for 24 h. The diguanidine-induced growth inhibition was fully reversed by low concentrations of exogenous polyamines. However, the possibility remained that the reversal by polyamines was due to a decrease of intracellular diguanidine concentration. Our results indicate that the mode of action of 1,1′-[(methylethanediylidene)dinitrilo]bis-(3-aminoguanidine) is fully comparable to that of methylglyoxal bis(guanylhydrazone), as regards stabilization of adenosylmethionine decarboxylase and the appearance of growth inhibition in Ehrlich ascites cells. The data tend to support the view that both compounds apparently have an early anti-proliferative effect unrelated to polyamine metabolism.


1976 ◽  
Vol 158 (3) ◽  
pp. 529-533 ◽  
Author(s):  
C A Manen ◽  
R L Blake ◽  
D H Russell

The PRO/Re strain of inbred mice are characterized by abnormally high concentrations of proline in both blood (hyperprolinaemia) and urine (prolinuria). They excrete increased amounts of polyamines in their urine. Male PRO/Re mice excreted putrescine at 175% and spermidine at 300% the amount of male C57BL/6J controls. Female PRO/Re mice excreted putrescine at 115% and spermidine at 150% of the amount in the urine of female controls. Examination of the enzymes involved in polyamine biosynthesis revealed that ornithine decarboxylase, the initial enzyme in the polyamine-biosynthetic pathway, was increased by 150% in the kidneys and by 100% in the liver of male PRO/Re mice. There was no significant difference between PRO/Re and C57BL/6J male mice for either putrescine- or spermidine-stimulated S-adenosylmethionine decarboxylase activity. Female PRO/Re mice showed no significant difference from female C57BL/6J mice for any of the enzymes examined. When the concentrations of the polyamines in the tissues of the PRO/Re mice were determined, spermidine and spermine concentrations in the kidneys of the male PRO/Re mice were twice those of the controls. Spermidine concentration in the livers of both male and female PRO/Re mice was approx. 130% that of the controls. Polyamine concentrations in the brains were similar in controls and mutants. The increased polyamine biosynthesis and excretion in the PRO/Re mutant mice may be a mechanism to decrease the extent of proline accumulation.


2017 ◽  
Vol 73 (4) ◽  
pp. 234-238
Author(s):  
Aleksandra Ewa Krawczyk ◽  
Jadwiga Jaworska-Adamu

The aim of the study was the immunohistochemical evaluation of the impact of the age of animals treated with the sodium salt of glutamic acid on the behaviour of astrocytes of the infundibular nucleus (IN). Immunohistochemical peroxidase-antiperoxidase reactions were conducted on brain sections of 10-day-old (I) and 63-day-old (II) rats treated s.c with monosodium glutamate (MSG) in a dose of 4g/kg b.w. for three consecutive days. The staining was performed using specific antibodies against glial fibrillary acidic protein (GFAP), S-100β protein and Ki-67 antigen. Cells immunopositive for the proteins under investigation were assessed morphologically and morphometrically in an Olympus BX51 light microscope with the Cell ^ D program. Statistically significant differences were tested using ANOVA and the non-parametric Kruskal-Wallis test. In the infundibular nucleus of 10-day-old rats treated with MSG, there was an increase in the number of GFAP, S-100β and Ki-67 immunopositive astrocytes without any changes in their morphology, which was typical of immature glia. In adult rats treated with MSG, a decrease in the number of cells expressing GFAP and S-100β was found. Most astrocytes had thick and weakly branched processes, in contrast to those observed in control animals. The results of our study showed a diverse behaviour of astroglia of IN in young and adult rats treated with MSG. In 10-day-old rats, hyperplasia of glia occurred, whereas in 63-day-old individuals there was a loss and hypertrophy of astrocytes, which may indicate a late stage of their reactivity. This information may contribute to targeting the therapy of diseases of the nervous system induced by the excitotoxic effects of glutamate.


1975 ◽  
Vol 151 (1) ◽  
pp. 67-73 ◽  
Author(s):  
H Pösö ◽  
R Sinervirta ◽  
J Jänne

1. S-Adenosyl-L-methionine decarboxylase (S-adenosyl-L-methionine carboxy-lyase, EC 4.1.1.50) was purified more than 1100-fold from extracts of Saccharomyces cerevisiae by affinity chromatography on columns of Sepharose containing covalently bound methylglyoxal bis(guanylhydrazone) (1,1′[(methylethanediylidene)dinitrilo]diguanidine) [Pegg, (1974) Biochem J. 141, 581-583]. The final preparation appeared to be homogeneous on polyacrylamide-gel electrophoresis at pH 8.4. 2. S-Adenosylmethionine decarboxylase activity was completely separated from spermidine synthase activity [5′-deoxyadenosyl-(5′),3-aminopropyl-(1),methylsulphonium-salt-putrescine 3-aminopropyltransferase, EC 2.5.1.16] during the purification procedure. 3. Adenosylmethionine decarboxylase activity from crude extracts of baker's yeast was stimulated by putrescine, 1,3-diamino-propane, cadaverine (1,5-diaminopentane) and spermidine; however, the purified enzyme, although still stimulated by the diamines, was completely insensitive to spermidine. 4. Adenosylmethionine decarboxylase has an apparent Km value of 0.09 mM for adenosylmethionine in the presence of saturating concentrations of putrescine. The omission of putrescine resulted in a five-fold increase in the apparent Km value for adenosylmethionine. 5. The apparent Ka value for putrescine, as the activator of the reaction, was 0.012 mM. 6. Methylglyoxal bis(guanylhydrazone) and S-methyladenosylhomocysteamine (decarboxylated adenosylmethionine) were powerful inhibitors of the enzyme. 7. Adenosylmethionine decarboxylase from baker's yeast was inhibited by a number of conventional carbonyl reagents, but in no case could the inhibition be reversed with exogenous pyridoxal 5′-phosphate.


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