Effect Of Spermine Research Articles

The Effect of e-, i-, and n-Nitric Oxide Synthase Inhibition on Colonic Motility in Normal and Muscular Dystrophy (Mdx) Mice

To explore the origin of diarrhea or constipation in human Duchenne muscular dystrophy (DMD), the effect of the inhibition of e- , i-, and n-nitric oxide synthase (NOS) on the motility of proximal and distal segments of colon of muscular dystrophy (mdx) and control mice was studied. The frequency of migrating motor complexes (MMC) was higher in the proximal than in the distal segments in mdx colon (0.56 vs. 0.25 cpm) and in the control colon (0.7 vs. 0.25 cpm), and there was no difference when mdx was compared to control segments. High concentrations of NOS inhibitors, including 1,3-PBIT dihydrobromide (1,3-PBIT) and spermine, inhibited MMC. The dose of spermine required to inhibit MMC was lower for the proximal mdx colon than for the distal mdx or control colon. In the presence of tetrodotoxin, spermine (1 mM) and 1,3-PBIT (5 mM) reduced the magnitude of local, rhythmic contractions (LC) paced by the interstitial cells of Cajal (ICC), but 1,3-PBIT (50 microM) increased their magnitude. There was no difference in the effect of spermine and 1,3-PBIT on the LC between mdx and control colon. The results suggest an inhibition of MMC by high concentrations of e-, i-, and n-NOS inhibitors, modulation of ICC activity by e-NOS, and greater susceptibility of MMC to n-NOS inhibition in the mdx proximal than in the control colon, which is very likely because of a deficit in n-NOS in the mdx smooth muscle affecting the MMC pacemaker. A deficit in the effect of mdx smooth muscle n-NOS on an MMC pacemaker may be the origin of diarrhea or constipation in human DMD.

Spermine reduces infarction and neurological deficit following a rat model of middle cerebral artery occlusion: a magnetic resonance imaging study

The role of nitric oxide (NO) in post-ischemic cerebral infarction has been extensively examined, but few studies have investigated its role on the neurological deficit. In the present study, we investigated the effect of spermine on the temporal evolution of infarct volume, NO production and neurological deficit using magnetic resonance imaging in a model of permanent focal cerebral ischemia in rats. Spermine given at 10 mg/kg 2 h after ischemia reduced the infarct volume by 40% and abolished brain NO production and improved the neurological score 24 h, 48 h and 72 h after ischemia. Spermine also reduced the neurological deficit as evaluated by rotamex, grip strength and neurological severity score tests.

Immunomodulatory action of spermine and spermidine on NR8383 macrophage line in various culture conditions

We examined the effect of spermine (SPM) and spermidine (SPD) on tumor necrosis factor (TNF)α and monocyte chemoattractant protein-1 (MCP-1) secretion from macrophages in various culture conditions, including several protocols of polyamines addition and media supplemented with 0, 1 or 15% fetal bovine serum. TNFα secretion was inhibited by SPM or SPD added 18 h before stimulation in a concentration-dependent manner. Their effect was directly related to the presence of FBS. When SPM or SPD was added simultaneously to the stimulus, the TNFα secretion inhibition was higher than that obtained after pre-treatment. In this case, the effect was inversely proportional to the presence of FBS. The addition of polyamines also inhibited the secretion of MCP-1 in NR8383 cells. We conclude that SPM and SPD inhibited the secretion of inflammatory cytokines TNFα and MCP-1 in different ways, depending on culture conditions. In any case, SPM was more effective than SPD.

The effects of spermine on the accessibility of residues in the M2 segment of Kir2.1 channels expressed in Xenopus oocytes.

We examined the effects of spermine binding to aspartate at site 172 on the accessibility of internal trimethylammonioethylmethane thiosulphonate (MTSET) to substituted cysteines within the pore of a Kir2.1 channel. Spermine prevented MTSET modification in Q164C and G168C mutants, indicating that sites 164 and 168 are located externally to the spermine binding site. The rates of MTSET modification were significantly reduced by spermine in I176C mutants, indicating that site 176 is located internally to D172 and that the bound spermine hinders the reaction of MTSET with cysteine at site 176. Spermidine, putrescine and Mg2+ also decreased MTSET modification at site 176. The order of effect is putrescine > spermidine approximately = spermine approximately = Mg2+. To account for the electrostatic and physical repulsion between MTSET and polyamines, possible locations of polyamines in the pore are discussed. In D172C mutants, the spermine that bound to sites 224 and 299 completely inhibited channels at +40 mV, yet MTSET remained accessible to site 172. In addition, in the D172C mutant, spermine did not affect the exit rate of Ba2+ bound to the threonine at the site 141. These results indicate that spermine bound at the cytoplasmic pore induces channel closure at positions 141-172. The effects of spermine on the accessibility of amino acids in the pore may shed light on the structural and functional relationships of the Kir2.1 channels during inward rectification.

폴리아민에 의한 양배추 포스포리파제 D의 활성화

The effect of polyamines on the cabbage phospholipase D(PLD) activity was investigated. The PLD activity was determined by pH-stat titration of phosphatidic acid, one of the enzymatic reaction product, using phos- phatidyl choline small unilamellar vesicles as a substrate. The cabbage PLD was activated approximately 4 fold by sper- mine at 1 mM concentration. This spermine effect appears to be similar to the previous report on the PLD activation of rat brain mitochondrial fraction. It was also found that cationic polypetides such as polylysine and polyhistidine exerted a marked enhancement effect on the cabbage PLD. Particularly polyhistidine exerted approximately 5.5 fold enhance- ment effect at 0.062 mM concentration. The polyamine effect on the cabbage PLD was reexamined in the phos- phatidylcholine/sodium dodecyl sulfate mixed micellar system. The relevance of polyamine effect on PLD activity is discussed in relation to the active site of PLD.

Effect of polyamines on the inhibition of peptidyltransferase by antibiotics: revisiting the mechanism of chloramphenicol action.

Chloramphenicol is thought to interfere competitively with the binding of the aminoacyl-tRNA 3'-terminus to ribosomal A-site. However, noncompetitive or mixed-noncompetitive inhibition, often observed to be dependent on chloramphenicol concentration and ionic conditions, leaves some doubt about the precise mode of action. Here, we examine further the inhibition effect of chloramphenicol, using a model system derived from Escherichia coli in which a peptide bond is formed between puromycin and AcPhe-tRNA bound at the P-site of poly(U)-programmed ribosomes, under ionic conditions (6 mM Mg2+, 100 mM NH4+, 100 microM spermine) more closely resembling the physiological status. Kinetics reveal that chloramphenicol (I) reacts rapidly with AcPhe-tRNA.poly(U).70S ribosomal complex (C) to form the encounter complex CI which is then isomerized slowly to a more tight complex, C*I. A similar inhibition pattern is observed, if complex C modified by a photoreactive analogue of spermine, reacts in buffer free of spermine. Spermine, either reversibly interacting with or covalently attached to ribosomes, enhances the peptidyltransferase activity and increases the chloramphenicol potency, without affecting the isomerization step. As indicated by photoaffinity labeling, the peptidyltransferase center at which chloramphenicol binds, is one of the preferred cross-linking sites for polyamines. This fact may explain the effect of spermine on chloramphenicol binding to ribosomes.

Effect of spermine synthase on the sensitivity of cells to anti-tumour agents.

The role of spermine in the sensitivity of cells to various established and experimental anti-tumour agents was examined, using paired cell lines that possess or lack spermine synthase. All spermine-synthase-deficient cells had no detectable spermine, and elevated spermidine, content. Spermine content did not alter the cell growth rate. There was little or no difference in sensitivity of immortalized mouse embryonic fibroblasts to doxorubicin, etoposide, cisplatin, methylglyoxal bis(guanylhydrazone) or H(2)O(2) and only a slight increase in sensitivity to vinblastine and nocodazole. However, the absence of spermine clearly increased the sensitivity to 1,3-bis(2-chloroethyl)- N -nitrosourea, suggesting that depletion of spermine may be a useful way to increase the anti-neoplastic effects of anti-tumour agents that form chloroethyl-mediated interstrand DNA cross-links. The effects of spermine on the response to polyamine analogues (which have been proposed to be useful anti-neoplastic agents) were complex, and depended on the compound examined and on the cells tested. Sensitivity to CHENSpm ( N (1)-ethyl- N (11)-[(cycloheptyl)methyl]-4,8-diazaundecane) was substantially greater in immortalized fibroblasts that lack spermine. In contrast, BE-3-4-3 [ N (1), N (12)-bis(ethyl)spermine] and BE-3-3-3 [ N (1), N (11)-bis(ethyl)norspermine] were more active against cells that contained spermine. The presence of spermine correlated with a greater induction of spermidine/spermine- N (1)-acetyltransferase by BE-3-3-3, which is consistent with suggestions that this induction is important for the response to this drug. These findings support the concepts that different polyamine analogues have different sites of action and that CHENSpm has a different site of action from BE-3-3-3.

Involvement of voltage- and ligand-gated Ca2+ channels in the neuroexcitatory and synergistic effects of putative uremic neurotoxins

Renal failure has been viewed as a state of cellular calcium toxicity due to the retention of small fast-acting molecules. We have tested this hypothesis and identified potentially neuroexcitatory compounds among a number of putative uremic neurotoxins by examining the acute in vitro effects of these compounds on cultured central neurons. The in vitro neuroexcitatory and synergistic effects of guanidinosuccinate and spermine were also examined in vivo. The acute effects of 17 candidate uremic neurotoxins on murine spinal cord neurons in primary dissociated cell culture were investigated using the tight-seal whole-cell recording technique. The compounds studied comprised low-molecular-weight solutes like urea, indoles, guanidino compounds, polyamines, purines and phenoles, homocysteine, orotate, and myoinositol. Currents evoked by these compounds were further examined using various ligand- and voltage-gated ion channel blockers. The acute in vivo effects of guanidinosuccinate and spermine were behaviorally assessed following their injection in mice. It was shown that 3-indoxyl sulfate, guanidinosuccinate, spermine, and phenol evoked significant whole-cell currents. Inward whole-cell current evoked by 3-indoxyl sulfate was not blocked by any of the applied ligand- or voltage-gated ion channel blockers, and the compound appeared to influence miscellaneous membrane ionic conductances, probably involving voltage-gated Ca2+ channels as well. Phenol-evoked outward whole-cell currents were at least partly due to the activation of voltage-gated K+ channels, but may also involve a variety of other ionic conductances. On the other hand, inward whole-cell currents evoked by guanidinosuccinate and spermine were shown to be due to specific interaction with voltage- and ligand-gated Ca2+ channels. Guanidinosuccinate-evoked current was caused by activation of N-methyl-d-aspartate (NMDA) receptor-associated ion channels. Low (micromol/L) concentrations of spermine potentiated guanidinosuccinate-evoked current through the action of spermine on the polyamine binding site of the NMDA receptor complex, whereas current evoked by high (mmol/L) concentrations of spermine alone involved direct activation of voltage-gated Ca2+ channels. Finally, intracerebroventricular administration of 0.25 micromol/L spermine potentiated clonic convulsions induced by guanidinosuccinate. These neuroexcitatory and synergistic effects of guanidinosuccinate and spermine could take place at pathophysiologic concentrations. The observed in vitro and in vivo effects of uremic retention solutes suggest that the identified compounds could play a significant role in uremic pathophysiology. Some of the compounds tested displayed in vitro and in vivo neuroexcitatory effects that were mediated by ligand- and voltage-gated Ca2+ channels. The findings suggest a mechanism for the involvement of calcium toxicity in the central nervous system complications in renal failure with particular reference to guanidinosuccinate and spermine.

Effect of spermine on the activity of synaptosomal plasma membrane Ca 2+-ATPase reconstituted in neutral or acidic phospholipids

The activity of purified plasma membrane Ca 2+-ATPase (PMCA) from pig brain was inhibited by spermine (a naturally occurring and highly abundant polycation in brain). The level of inhibition was dependent on the phospholipid used for reconstitution as well as on the intact or truncated state of the enzyme. An IC 50 value of 12.5 mM spermine was obtained for both, the intact protein plus calmodulin and the trypsin-digested protein, reconstituted in phosphatidylcholine (PC). In the absence of calmodulin the intact Ca 2+-ATPase gave an IC 50 of 27 mM. This form was more sensitive to spermine inhibition when it was reconstituted with phosphatidylserine (PS), showing an IC 50 value of 2.5 mM spermine. However, the truncated form was less responsive to spermine inhibition, having an IC 50 value of 12.5 mM. Spermine has no effect on the affinity of the PMCA for Ca 2+ or ATP, but its effect on the protein is pH-dependent. It is suggested that spermine could bind to negatively charged residues on the ATPase with different accessibility, depending on the structural rearrangement of the protein. Further, when the protein is reconstituted in PS, spermine also binds to the lipid.

Ameliorative effects of histamine on 7-chlorokynurenic acid-induced spatial memory deficits in rats.

Histamine plays an important role in modulating acquisition and retention in learning and memory process in experimental animals. We examined the effects of polyamine and histamine on the N-methyl- d-aspartate (NMDA) receptor glycine site antagonist 7-chlorokynurenic acid-induced spatial memory deficits in radial maze performance in rats. Effects of histamine (0.5 or 1 nmol/site intracerebroventricularly), spermidine (1 nmol/site, intracerebroventricularly) and spermine (1 nmol/site, intracerebroventricularly) on spatial memory deficit in 9-week-old-male Wistar rats were observed. Both reference and working memory errors occurred in radial maze performance in rats, following intracerebroventricular injection of 7-chlorokynurenic acid (10 nmol/site). Spermidine (1 nmol/site, intracerebroventricularly) or spermine (1 nmol/site, intracerebroventricularly) antagonized 7-chlorokynurenic acid-induced deficits on working memory but not on reference memory errors. Intracerebroventricular histamine (0.5 or 1 nmol/site) or thioperamide (100 nmol/site) also ameliorated 7-chlorokynurenic acid-induced working memory deficits. To determine whether the effects of histamine involve histamine receptors, the effects of some methylhistamines were examined. The effects of R-alpha-methylhistamine on radial maze performance were mimicked by histamine. N(alpha)-methylhistamine had no effect on 7-chlorokynurenic acid-induced memory deficits, whereas 1-methylhistamine, but not 3-methylhistamine reversed 7-chlorokynurenic acid-induced working memory deficits. These results suggest that the amelioration of 7-chlorokynurenic acid-induced working memory deficits by histamine may involve a direct action of histamine at the polyamine sites on NMDA receptors.

Ambiol, spermine, and aminoethoxyvinylglycine prevent water stress and protect membranes in Pinus strobus L under drought

The ability of antistress compounds to enhance the drought tolerance of conifer seedlings was tested by feeding plant growth regulators (PGRs) to 1-year-old white pine (Pinus strobus L.), which were then subjected to either a moderate (11 day) or a more severe (16 day) drought. The following PGRs were either fed directly into the xylem or applied as a root drench: the antioxidant Ambiol (2-methyl-4-[dimethylaminomethyl]- 5-hydroxybenzimidazole dihydrochloride), the polyamine, spermine, an anti-ethylene agent, aminoethoxyvinylglycine (AVG), and the inhibitor, abscisic acid (ABA). Leaf water potentials (Ψl) declined in untreated seedlings when they were exposed to drought. Preconditioning with PGRs postponed water deficits and prevented membrane leakage under drought. The specific physiological adjustments observed were found to vary, depending on the type of compound. Ambiol, AVG and spermine caused transpirant rates to decline under drought. Although the antitranspirant effects of Ambiol and spermine would explain the increase in water use efficiency under drought, spermine also enhanced photosynthesis. The same compounds promoted osmotic adjustment, which would help to maintain turgor under drought. This was shown by the decline in osmotic potential at full turgor, and at zero turgor, in Ambiol and spermine-treated seedlings. Seedlings treated with Ambiol and ABA could sustain a greater water loss before turgor declined to zero. The possibility that preconditioning may help to maintain leaf physiological functioning under drought by reducing water stress and stress-ethylene production is discussed.

Voltage-Dependent Blockade of Connexin40 Gap Junctions by Spermine

The effects of spermine and spermidine, endogenous polyamines that block many forms of ion channels, were investigated in homotypic connexin (Cx)-40 gap junctions expressed in N2A cells. Spermine blocked up to 95% of I j through homotypic Cx40 gap junctions in a concentration- and transjunctional voltage ( V j)-dependent manner. V j was varied from 5 to 50 mV in 5-mV steps and the dissociation constants ( K m) were determined from spermine concentrations ranging from 10 μM to 2 mM. The K m values ranged from 4.9 mM to 107 μM for 8.6 ≤ V j ≤ 37.7 mV, within the physiological range of intracellular spermine for V j ≥ 20 mV. The K m values for spermidine were ≥ 5 mM. Estimates of the electrical distance ( δ) for spermine ( z = +4) and spermidine ( z = +3) were 0.96 and 0.76 respectively. Cx40 single channel conductance was 129 pS in the presence of 2-mM spermine and channel open probability was significantly reduced in a V j-dependent manner. Similar concentrations of spermine did not block I j through homotypic Cx43 gap junctions, indicating that spermine selectively blocks Cx40 gap junctions. This is contrary to our previous findings that large tetraalkylammonium ions, also known to block several forms of ion channels, block junctional currents ( I j) through homotypic connexin Cx40 and Cx43 gap junctions.

Effect of polyamines on in vitro platelet aggregation and in vivo thrombus formation

Introduction: 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 inhibited platelet activation, but there were no definitive studies testing their efficacy in an in vivo thrombosis model. We carried out detailed in vitro platelet aggregation studies using various concentrations of polyamines as well as agonists. Methods: Platelet aggregation was measured by a turbidimetric method. Electric current induced in vivo thrombosis model is used for assessing antithrombotic effect. Incidence of bleeding was evaluated by template bleeding and incisional bleeding. Results: Polyamines inhibited agonist-induced platelet aggregation in a dose-dependent manner. The inhibitory effect of polyamines is inversely proportional to the concentration of the agonist used. Among the polyamines, spermine is the potent inhibitor of platelet aggregation. A partially occlusive thrombus was generated by application of electric current in canine coronary artery. In control animals, the artery was completely occluded in 70±11 min after the current was discontinued. Blood flow remained patent for >240 min when 2 mg/kg spermine was given immediately after stopping the current. The antithrombotic effect of spermine was not associated with increased bleeding tendency. Conclusion: These results indicate that apart from inhibiting in vitro platelet aggregation polyamines can also inhibit in vivo thrombus formation. To our knowledge, this is the first study demonstrating this phenomenon.

The identification of spermine binding sites in 16S rRNA allows interpretation of the spermine effect on ribosomal 30S subunit functions.

A photoreactive analogue of spermine, N1-azidobenzamidino (ABA)-spermine, was covalently attached after irradiation to Escherichia coli 30S ribosomal subunits or naked 16S rRNA. By means of RNase H digestion and primer extension, the cross-linking sites of ABA-spermine in naked 16S rRNA were characterised and compared with those identified in 30S subunits. The 5' domain, the internal and terminal loops of helix H24, as well as the upper part of helix H44 in naked 16S rRNA, were found to be preferable binding sites for polyamines. Association of 16S rRNA with ribosomal proteins facilitated its interaction with photoprobe, except for 530 stem-loop nt, whose modification by ABA-spermine was abolished. Association of 30S with 50S subunits, poly(U) and AcPhe-tRNA (complex C) further altered the susceptibility of ABA-spermine cross-linking to 16S rRNA. Complex C, modified in its 30S subunit by ABA-spermine, reacted with puromycin similarly to non-photolabelled complex. On the contrary, poly(U)-programmed 70S ribosomes reconstituted from photolabelled 30S subunits and untreated 50S subunits bound AcPhe-tRNA more efficiently than untreated ribosomes, but were less able to recognise and reject near cognate aminoacyl-tRNA. The above can be interpreted in terms of conformational changes in 16S rRNA, induced by the incorporation of ABA-spermine.

Polyamine effects on human myometrial contractility

Objective: This study was undertaken to investigate the effects of the polyamine spermine on human uterine contractility. Study design: Under physiologic conditions, an isometric tension recording was performed in isolated myometrial strips from biopsy specimens obtained at elective cesarean delivery (n = 24 specimens) and from premenopausal hysterectomy specimens (n = 6 specimens). The effects of spermine (1 μmol/L-10 mmol/L in cumulative doses) on spontaneous, agonist-induced myometrial contractions were measured, and dose response curves were constructed. The pD2 (−log EC50) values and the maximal inhibition values achieved were compared for spontaneous and agonist-induced contractions. Results: Spermine exerted a potent relaxant effect on all spontaneous and agonist-induced myometrial contractions, with mean maximal inhibition values between 62.8% ± 4.3% and 91.4% ± 1.8% and pD2 values between 2.66 ± 0.23 and 4.01 ± 0.20. Its inhibitory effect varied significantly with different contraction types (pD2, P < .05; mean maximal inhibition, P < .001), and it was least potent on BAY K 8644-elicited contractions (pD2, P < .05; mean maximal inhibition, P < .01). Conclusion: The polyamine spermine exerts a potent relaxant effect on human uterine tissue. This effect appears to be mediated, at least partially, by calcium antagonism. Polyamines may play a role in the maintenance of uterine quiescence during pregnancy. (Am J Obstet Gynecol 2002;186:778-83.)

Activation of N-acylethanolamine-releasing phospholipase D by polyamines

N-acylethanolamines including anandamide (an endogenous ligand of cannabinoid receptors) are biosynthesized from N-acyl-phosphatidylethanolamine (PE) by a phosphodiesterase of the phospholipase D type. The enzyme partially purified from the particulate fraction of rat heart hydrolyzed N-palmitoyl-PE to N-palmitoylethanolamine with a specific activity of 50 nmol/min per mg protein at 37 °C in the presence of 10 mM CaCl 2. We found that the enzyme was highly activated in dose-dependent manner by polyamines like spermine, spermidine, and putrescine. Spermine was the most potent with an EC 50 value around 0.1 mM, and increased the specific enzyme activity 27 fold up to 53 nmol/min per mg protein. However, a synergistic effect of spermine and the known activator (Ca 2+ or Triton X-100) was not observed. The spermine-stimulated enzyme was also active with N-arachidonoyl-PE (a precursor of anandamide). Thus, polyamines may function as endogenous activators to control the biosynthesis of anandamide and other N-acylethanolamines.

The effect of spermine on plasmid condensation and dye release observed by fluorescence correlation spectroscopy.

We demonstrate that fluorescence correlation spectroscopy (FCS) can be employed to follow the conformational changes of DNA molecules induced by the addition of a cationic condensing compound (spermine). In our experiments the plasmid pHbetaAPr-1-neo (10 kbp; contour length 3.4 microm) was labeled with propidium iodide (PrIo) and then titrated with spermine to induce its condensation. When spermine was applied at concentrations above 5 microM (spermine/DNAphosphate=0.375), the diffusion time of the labeled plasmid dropped from 15 ms down to 3 ms (its diffusion coefficient, D, increased from 1.0x10(-12) m2/s to 6.0x10(-12) m2/s). The application of spermine was also accompanied by decreasing count rate and particle number, reflecting the dye's dissociation. The data presented show that FCS may become a valuable tool in studying supramolecular aggregate formation, especially when association is followed by a change in the hydrodynamic size of the resulting complex.

MODULATION BY POLYAMINES OF γ-GLUTAMYL TRANSPEPTIDASE ACTIVITY AND LACTATE PRODUCTION IN CULTURED SERTOLI CELLS FROM IMMATURE AND ADULT REGRESSED GOLDEN HAMSTER

Polyamines are involved in cellular growth and differentiation. To analyze a possible role of polyamines on the regulation of Sertoli cell function, we studied the effect of putrescine, spermidine, and spermine on γ-glutamyl transpeptidase (γ-GTP) activity and lactate production on Sertoli cell cultures obtained from immature and adult-regressed golden hamsters. Sertoli cells were cultured for 7 days. The 72 hour conditioned media obtained on day 6 were used to evaluate lactate levels. Gamma glutamyl transpeptidase activity was determined in the cells harvested on day 7. Cultured Sertoli cells isolated from immature and adult-regressed golden hamsters exhibited a clear morphological response to follicle-stimulating hormone (FSH) and to spermine. Gamma glutamyl transpeptidase activity increased in response to FSH in a dose-dependent manner. Dose-dependent stimulation of lactate production by FSH was also observed. For each functional parameter, a similar ED50 value of FSH stimulation was observed in both groups of animals. Spermine increased basal and FSH-stimulated γ-GTP activity in immature and adult-regressed Sertoli cell cultures. A stimulatory effect of spermidine and putrescine on γ-GTP activity was exclusively observed in adult-regressed Sertoli cell cultures. In Sertoli cells obtained from immature hamsters, spermine exerted a stimulatory effect on basal and FSH-stimulated lactate production.These results suggest that, in addition to the known effects of hormones and paracrine factors, polyamines may influence the functionality of Sertoli cells.

Synergistic Effects of Exogenous Spermine and Jasmonic Acid on the Volatile Production in Lima Bean Leaves(Abstracts of The 37th Annual Meeting of the Japanese Society for Chemical Regulation of Plants)

Synergistic Effects of Exogenous Spermine and Jasmonic Acid on the Volatile Production in Lima Bean Leaves(Abstracts of The 37th Annual Meeting of the Japanese Society for Chemical Regulation of Plants)

Oxidation products of polyamines induce mitochondrial uncoupling and cytochrome c release

Spermine is shown to uncouple isolated mitochondria and to trigger the selective release of cytochrome c. Pargyline, an inhibitor of amine oxidase (AO), fully prevented these effects of spermine, which instead were potentiated by exogenous AO. Hydrogen peroxide, an oxidation product of spermine, mimicked the effects of spermine on mitochondria, while the addition of catalase prevented them. Spermidine and putrescine also caused mitochondrial uncoupling and triggered cytochrome c release, with a potency which correlated with the substrate preference of mitochondrial AO. Pargyline protected human lymphoma U937 cells against UVB-induced apoptosis, by reducing AO activity, mitochondrial uncoupling and cytochrome c release.