Uptake of polyamines by human lymphocytes and their effect on lactate formation from glucose.
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Biomedical subjects
Publications and source records attributed to S Colombatto.
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The effect of turpentine, a chemical inflammatory agent, on polyamine synthesis has been studied. Ornithine decarboxylase activity is markedly increased in liver 6 hrs after subcutaneous injection of turpentine, and then decreases. No significant modification is observed in S-adenosylmethionine decarboxylase. Putrescine injected prior to turpentine prevents this increase. Putrescine, spermidine and spermine concentrations are all increased following turpentine, but with different patterns: spermidine alone keeps increasing for 50 hours. Putrescine and spermidine injected prior to turpentine partially counteract the increase of serum alpha 2-macroglobulin, which is believed to be a marker of inflammation.
1. When injected i.p., sodium selenite promoted a marked increase of rat liver ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMDC) activities; when administered with the diet for 6 weeks, a less marked increase in liver ODC was observed, whereas SAMDC was not significantly changed. 2. Protein synthesis was involved in the observed modifications. The rate of ODC inactivation was also changed. 3. ODC increase was accompanied by an enhanced putrescine concentration in liver. 4. A marked increase of ODC, accompanied by an enhancement of putrescine, was promoted by selenite (i.p.) also in chicken liver, together with an enhancement of glutathione concentration. Spermidine acetyltransferase (SAT) was also increased. 5. In the bursa of Fabricius, SAT activity was also increased, whereas ODC was decreased. However the expected modifications in polyamine concentration were not observed. 6. Decrease of ODC activity in the bursa was not due to an antizyme. 7. In vitro, selenite concentrations known to inhibit cell proliferation (greater than 1 microgram/ml) inhibited both ODC and SAT activities; at lower concentration, SAT activity was enhanced.
Vanadate in the presence of pyridoxal phosphate promotes the decarboxylation of S-adenosylmethionine. Pyridoxal has a lower effect; pyridoxine none. The rate of decarboxylation depends on pyridoxal phosphate and vanadate concentration. Vanadate as low as 10(-7) M gives significant decarboxylation. The reaction seems to occur through the formation of a Schiff base. The spectral shift elicited by S-adenosylmethionine on pyridoxal phosphate due to the presence of the sulfonium function is influenced by vanadate. Orthovanadate is a little less effective then metavanadate; vanadyl sulfate is even less efficient, and the effect of Cu2+ at the same concentration is still lower. Bleomycin partially prevents the vanadium effect. In vivo, vanadate promotes a marked increase in chicken liver S-adenosylmethionine and S-adenosylhomocysteine concentration, whereas the polyamine concentration is unaffected.
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Prolonged treatment with caffeine promotes in rats an increase of liver ornithine carbamyltransferase activity (14-day treatment). In contrast, arginase activity is already reduced in brain and kidney after 10 days, and in the liver much later (17 days). Ornithine transaminase activity was increased in both liver and kidney, while in the brain it was reduced (17 days). Ornithine decarboxylase activity showed only minor modifications in kidney, while it was unchanged in brain. Of the polyamines, only spermidine was significantly modified, being increased in brain, decreased in liver and kidney. Although these results do not explain the mechanism of the modification of brain arginine and ornithine concentration promoted by caffeine, they point to further marked effects, i.e. on OAT activity and on spermidine concentration, which could have a relevant metabolic role.
BACKGROUND: As previous studies demonstrated, free polyamines (putrescine, spermidine and spermine) are increased in neoplastic tissue and in body fluid (blood, urine and spinal fluid) of patients with tumours in various localization. In pediatric oncology, there aren't many specific markers useful to screen subjects at risk of developing cancer or to follow-up after treatment. For these reasons, polyamines' levels in plasma and erythrocytes have been evaluated in three groups of patients: healthy, with acute leukemia and with solid tumour. METHODS: Polyamines' content has been determined on samples of blood, previously dansylated, by HPLC (high performance liquid chromatography). RESULTS: The results of this study show that putrescine is decreased in plasma of patients with acute leukemia and with solid tumours. The difference, even if more important in subjects with leukemia, is significant in both groups. Spermidine instead, shows an increase, but only in patients with solid tumour. Erythrocyte assays reveal a significant decrease of spermidine in subjects with acute leukemia with consequent inversion of spermidine/spermine ratio. In erythrocytes there aren't any other significant changes in relation to the levels observed in healthy patients. Polyamine assay, especially that of putrescine and spermidine in plasma, could be propounded as a marker for pediatric neoplasms. CONCLUSIONS: Moreover, as it is well-known, pediatric neoplasms lead to alterations of polyamine metabolism, because the synthesis and catabolism of these molecules is closely involved in tumoral growth. Consequently, inhibitors of polyamine synthesis could be used with success in antineoplastic chemotherapy.