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22.
Incorporation of [14C]acetate was used as an index of acetylation of histone fractions in rabbit hearts. Spermine (10?6 and 10?5m) enhanced acetylation of all histone fractions in myocardial purified nuclei. In perfused hearts, spermine increased acetylation only in arginine-rich histone fractions. During the early stage of myocardial hypertrophy, a condition associated with a rise in the spermine content in the heart, an increased incorporation of [14C]acetate into F2a2 and F2a1 histone fractions was observed. From the results, a possible role of spermine in the mechanism of gene derepression is postulated. 相似文献
23.
Räsänen T.-L. Alhonen L. Sinervirta R. Uimari A. Kaasinen K. Keinänen T. 《Scandinavian journal of gastroenterology》2013,48(7):787-793
Background: The male antifertility agent gossypol has been reported to induce spermidine/spermine N 1 -acetyltransferase (SSAT) in canine prostate cells. As SSAT is the rate-controlling enzyme in the catabolism of the polyamines and is involved in the development of acute pancreatitis in a recent transgenic rat model, we exposed normal and transgenic rats over-expressing SSAT to gossypol to evaluate its effect on pancreatic polyamine metabolism and organ integrity. Methods: Pancreatic SSAT activity, polyamine pools, pancreatic histology and plasma ! -amylase activity were determined after different doses of gossypol. Results: Gossypol increased pancreatic putrescine and decreased spermidine and spermine pools in normal rats accompanied by tissue oedema and significantly elevated plasma amylase activity. In transgenic rats, the drug strikingly induced SSAT, profoundly depleted the higher polyamines and caused distinct pancreatitis. The combination of gossypol at doses harmless to transgenic pancreas with an inhibitor of polyamine oxidase caused massive synergistic induction of SSAT, profound depletion of the polyamine pools and acute pancreatitis. Conclusions: The results indicate that gossypol induces pancreatitis through an activation of polyamine catabolism. 相似文献
24.
Recent findings indicate that rapid and transient changes in polyamine metabolism, termed the polyamine-stress-response, may occur repeatedly in the brain after chronic intermittent stress. Here, we sought to examine the effects of chronic intermittent restraint stress, or of daily intraperitoneal dexamethasone injections on polyamine concentrations in the hippocampus of adult male C57BL/6 mice. Additionally, we studied the effects of alpha-difluoromethylornithine, an irreversible ornithine decarboxylase inhibitor, on stress-induced changes in polyamines and on behavioral reactivity to novelty stress measured in an open-field arena. As previously observed, following a single stress episode putrescine concentration increased transiently, but the polyamines spermidine and spermine remained unchanged. Following chronic restraint stress, putrescine concentration was increased after each daily stress episode with the largest increase observed after the 4th episode, while spermidine was increased just after the 2nd and 4th episodes and spermine only after the 4th daily episode. In contrast, all polyamine concentrations were increased after 10 injections of either dexamethasone or vehicle (0.9% NaCl). A 14-day course of alpha-difluoromethylornithine treatment resulted in a complete putrescine depletion and over 50% reduction in polyamines, and led to changes in open field activity indicative of altered emotional behavior. CONCLUSIONS: (a) while putrescine concentration increases in the hippocampus after each restraint stress episode, spermidine and spermine undergo a delayed but transient increase; (b) in contrast, chronic dexamethasone treatment may lead to a permanent increase in the concentrations of all polyamines and; (c) chronic alpha-difluoromethylornithine treatment reduces brain polyamine concentrations and modulates emotional reactivity to novelty stress. The study indicates that the brain polyamine-stress-response is a dynamic process that varies with the type, intensity and length of stressful stimuli, and implicates this response as an adaptive mechanism in the reaction to stressors. 相似文献
25.
Elizabeth Lynne Conway 《Brain research》1998,800(1):691
The effects of spermine on the acquisition and retention of spatial learning in the Morris water maze were studied. Spermine 25 and 125 nmol i.c.v. did not alter the ability of rats to find a hidden platform in the water maze when administered before training over 5 days. However, the inhibitory effect of the benzodiazepine, diazepam (3 mg/kg i.p., 30 min prior to training), on path length to target was markedly potentiated by the higher dose of spermine, consistent with spermine acting as a functional antagonist at the NMDA receptor. This drug combination did not affect performance on visible platform trials. Administration of doses of 125 and 250 nmol (but not 62.5 nmol) of spermine i.c.v. in the week prior to training (daily for 5 days) dose-dependently inhibited subsequent learning of a platform position in the absence of drug. These higher doses of spermine produced neuronal loss and increased
binding indicating microglial activation predominantly in the hippocampus and to a lesser extent in the striatum, septum, thalamus and amygdala. Spermine 125 nmol i.c.v. (daily for 7 days) also abolished retention of a previously learned platform position when administered in an interval between training and retention testing. The inhibitory effects of spermine 125 nmol i.c.v. (daily for 7 days) on subsequent spatial learning were not antagonised by concomitant administration of 30 nmol dizocilpine. These results demonstrate that spermine produces a delayed neurotoxic effect in particular neuronal populations in the brain that selectively impair spatial learning and recall. 相似文献
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26.
The ability of nitrendipine, nisoldipine, verapamil and gabapentin to inhibit the development of CNS excitation induced by spermine was assessed in mice. Injection of an excitotoxic dose of spermine (100 μg, i.c.v.) in mice results in worsening tremor that culminates in the development of a fatal tonic convulsion within 8 h of spermine administration. The dihydropyridines, nitrendipine and nisoldipine, which are L-type calcium channel antagonists acting at the 1 subunit, inhibited the development of spermine-induced effects. Verapamil, which also acts at the 1 subunit of the L-type calcium channel, also inhibited the development of spermine-induced CNS excitation. Gabapentin, a postulated L-type calcium channel antagonist interacting at the 2δ subunit, did not inhibit the development of spermine-induced effects. These results show that antagonists of the 1 subunit of L-type calcium channels can effectively inhibit the effects of spermine in vivo. This may highlight the importance of L-type calcium channels in spermine action. 相似文献
27.
Polyamines can modulate activation of N-methyl-d-aspartate (NMDA) receptors by binding to a specific polyamine site associated with a NMDA receptor macrocomplex. Polyamines induce histamine release from mast cells, although the mechanism had not been defined. We have examined whether spermine, a natural polyamine, and compound , regarded as a synthetic polyamine, activate mast cells by a polyamine site associated with a NMDA receptor macrocomplex. Spermine induced secretion of histamine from rat peritoneal mast cells and rat brain mast cells in a concentration-dependent manner. Rat peritoneal mast cells were used as a model system to explore the effects of NMDA antagonists on polyamine-induced histamine release. Ifenprodil, MK801 and arcaine inhibited histamine secretion from mast cells exposed to polyamines; the percentage inhibition was greater against spermine than compound . These data support the proposal that spermine (and possibly compound ) induce histamine release from mast cells by interacting with a specific polyamine site on a NMDA receptor complex. 相似文献
28.
Patrick Merkel Alexander Beck Khalid Muhammad Syed Abid Ali Caroline Sch?nfeld Wolfgang Voelter Michael Duszenko 《Toxicon》2007,50(4):457-469
The snake venom from the leaf-nosed viper Eristocophis macmahoni was analyzed regarding its toxic effects on the bloodstream form of Trypanosoma brucei. A considerable trypanocidal effect was measured with an IC5 value of 186 ng/ml in bloodstream form parasites. Following several high performance liquid chromatography (HPLC) separation steps, the major trypanocidal activity was assigned to a single fraction by in vitro toxicity assays. Analysis by off-line ESI-MS(n) revealed an m/z value of 202.2 for the precursor ion and fragment ions of m/z=129.1 (MS2) and 112.1 (MS3), respectively, clearly corresponding to the molecular mass and the fragmentation pattern of the polyamine spermine. Quantification of spermine within the viper venom using an on-line hydrophilic interaction chromatography (HILIC) ESI-MS method revealed that this compound constituted approximately 1% of the dry venom mass. The polyamine oxidase activity in the fetal calf serum used for cultivation was responsible for a trypanocidal effect of pure spermine in the low micromolar range, whereas the antitrypanosomal activity of crude snake venom was virtually independent from serum, suggesting the oxidation of spermine by intrinsic venom components. Using fetal calf serum, spermine was shown to induce autophagy in the parasites using transmission electron microscopy (TEM). 相似文献
29.
Pakala R 《Thrombosis research》2003,110(1):47-51
Polyamines are polycations present in all living organisms and have been shown to play an important role in various physiological functions. Previous studies have shown that various amines including polyamines inhibit platelet activation. Among the amines tested tetra-amine, spermine is the potent inhibitor of platelet aggregation. In spite of vast literature on the anti-aggregatory effect of amines, there are no definitive studies testing their efficacy in an in vivo thrombosis model. In the present study, we investigated if polyamines could inhibit in-vivo thrombosis. A partially occlusive thrombus was generated by application of electric current in canine coronary artery. In control animals, the artery was completely in 76+/-14 min after the current was discontinued. When 40 mg/kg (1.44 mM) spermine was given immediately after stopping the current blood flow remained patent for >240 min. At equimolar concentration, triamine, spermidine and diamine putrescine are also equally effective in preventing thrombus development. The anti thrombic effect of polyamines was not associated with increased bleeding tendency, as judged by the amount of blood adsorbed by a gauge pad placed in a surgical incision extending to the muscle tissue and by a standard template bleeding. These results indicate that apart from inhibiting in-vitro platelet aggregation polyamines can also inhibit in-vivo thrombus formation. 相似文献
30.
Spermine-induced negative inotropic effect in isolated rat heart,is mediated through the release of ATP 总被引:1,自引:0,他引:1
Guevara-Balcázar G Querejeta-Villagómez E Nuevo-Adalla O Orozco-Guillen A Rubio-Gayosso I Hernández-Castillo JR Zamora-Garza M Ceballos-Reyes G 《Biochemical pharmacology》2003,66(1):157-161
Putrescine, spermidine and spermine are natural compounds found in up to millimolar concentrations in eukaryotic and prokaryotic cells. At physiologic pH, the polyamines are protonated (+2, +3 and +4 charges), their polycationic properties lead to the assumption that they could affect physiological systems by binding to anionic sites of the cellular membrane and/or by modulating ion channels. At the cardiovascular level, their effects are not completely understood. However, these compounds may be able to exert the induction of synthesis and release of cellular mediators. In an attempt to explore this possibility, we used the isolated and perfused rat heart, Langendorff, model in order to evaluate the inotropic effects of these polyamines, putrescine, spermidine and spermine. Dose-response curves (0.1-0.6 mM) for putrescine, spermidine and spermine were constructed; with the finding that spermine had the largest negative effect. The obtained effects were not blocked by nitric oxide synthesis inhibitors (L-NAME), H(1) and H(2) receptor antagonists (Brompheniramine and Cimetidine) or by Glibenclamide, an antagonist of ATP-sensitive K(+) channels. We found that spermine-induced and increased ATP concentration in cardiac effluents. Reactive Blue, a P(2y) purinoreceptor antagonist and Aminophylline, an unspecific adenosine receptor antagonist, blocked the spermine-induced effects. These results showed that ATP, at least in part, is responsible of the spermine cardiovascular effects. Adenosine was shown to also play an important role on those effects. 相似文献