Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Spermine”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1990

Combined regulation of ornithine and S-adenosylmethionine decarboxylases by spermine and the spermine analogue N1 N12-bis(ethyl)spermine.

In the present study, the spermine (SPM) analogue N1N12-bis(ethyl)spermine (BESPM) is compared with SPM in its ability to regulate ornithine decarboxylase (ODC) and S-adenosyl-L-methionine decarboxylase (AdoMetDC) activities in intact L1210 cells and in the mechanism(s) by which this is accomplished. Unlike the comparable spermidine (SPD) analogue N1N8-bis(ethyl)spermidine, which regulates only ODC, BESPM suppresses both ODC and AdoMetDC activities. With 1 microM-SPM or -BESPM, near-maximal suppression of enzyme activity (i.e. less than 70%) was achieved after 2 h for ODC and 12 h for AdoMetDC. After such treatment, ODC activity fully recovered within 2-4 h, and that of AdoMetDC within 12 h, when cells were reseeded into drug-free media. It was deduced that an intracellular accumulation of BESPM or SPM equivalent to only approximately 200-450 pmol/10(6) cells was sufficient to fully invoke ODC regulatory mechanisms. Decreases in both enzyme activities after BESPM or SPM treatment were closely paralleled by concomitant decreases in the amount of enzyme protein. Since cellular ODC or AdoMetDC mRNA was not similarly decreased by either BESPM or SPM treatment, it was concluded that translational and/or post-translational mechanisms were probably responsible for enzyme regulation. In support of the former of these possibilities, it was demonstrated that both BESPM and SPM preferentially inhibited the translation in vitro of ODC and AdoMetDC relative to albumin in a reticulocyte-lysate system. On the basis of the consistent similarities between BESPM and SPM in all parameters studied, it is concluded that the analogue most likely acts by mechanisms identical with those by which SPM acts in suppressing polyamine biosynthesis.

Adenosylmethionine Decarboxylase↗
PubMed1991

1H and 31P nuclear magnetic resonance studies of spermine binding to the Z-DNA form of d(m5CGm5CGm5CG)2. Evidence for decreased spermine mobility.

The binding of spermine to the d(m5CGm5CGm5CG) duplex has been studied by proton and phosphorus nuclear magnetic resonance techniques in order to investigate the mobility and nature of spermine bound to the resulting Z-DNA complex. A characterization of the B to Z transition as a function of increasing spermine concentration demonstrated doubling of the non-exchangeable proton and the phosphorus peaks at a ratio of about 1:1 (spermine/duplex) and a re-simplification of the spectrum at 2:1 (spermine/duplex) where about 90% or the DNA was fully converted into the Z-form. However, some of the Z-DNA proton chemical shifts differed between the 1:1 and 2:1 titration points. Since these differences involved primarily the exchangeable terminal imino and amino protons, they could result from end effects. Discrepancies were generally not observed with the non-terminal proton shifts nor with the phosphorus shifts. These proton and phosphorus chemical shift changes are fully consistent with a B to Z transition. Complexed spermine peaks appear about 0.1 parts per million upfield from the uncomplexed form. The spermine and both the B and Z-DNA hexamer signals are noticeably broadened at the 1:1 ratio but the remaining signals re-sharpen at the 2:1 ratio. Both one-dimensional and two-dimensional studies revealed negative nuclear Overhauser effect (NOE) contacts between each spermine proton. Therefore, spermine has a longer correlation time than that observed for unbounded spermine. These results are contrasted with the positive NOE contacts observed for the B-DNA-spermine complexes reported by Wemmer et al. using the dodecamer d(CGCGAATTCGCG)2 and reported here using the hexamer d(ATGCAT)2. While the mobility of spermine in the Z-DNA complex is significantly less than that of the B-DNA complex, no clear evidence of intermolecular spermine-DNA proton NOE contacts is observed.

Base Sequence↗
PubMed1976

Stimulation of RNA polymerases I, II and III from rat liver by spermine, and specific inhibition of RNA polymerase I by higher spermine concentrations.

Spermine stimulates activities of higherly purified rat liver nuclear RNA olymerases I, II and III 3 to 4 fold. Inclusion of (NH4)2SO4 at concentrations required for maximal enzyme activities does not significantly enhance the degree of stimulation of polymerase activities by spermine, but maintains the stimulatory levels of enzymes over a broader range of spermine concentrations. The stimulatory effect of spermine at a concentration of 1 mM is a useful method for the elevation of activities of all RNA polymerases and thus provides a means to measure these enzymes when extracted from small quantities of tissues or cells. Based on the differential stimulation of the polymerases by spermine, a higher concentration of spermine (5 mM) can be selected to inhibit RNA polymerase I specifically.

Animals↗
PubMed1991

Correlation between spermine stimulation of rat liver Ile-tRNA formation and structural change of the acceptor stem by spermine.

We have recently reported that the interaction of spermine with the acceptor and anticodon stems may be important for spermine stimulation of rat liver Ile-tRNA formation [Peng, Z. et al. (1990) Arch. Biochem. Biophys. 279, 138-145]. To pinpoint which interaction of spermine is more important for spermine stimulation of Ile-tRNA formation, Ile-tRNA formation and ribonuclease V1 sensitivity of tRNA(Ile) were studied using purified tRNAs(Ile) from rat liver, wheat germ, brewer's yeast, torula yeast and Escherichia coli. The results indicate that spermine stimulation of rat liver Ile-tRNA formation correlated with the structural change of the acceptor stem by spermine. The nucleotide sequence of wheat germ tRNA(Ile) was also determined.

Acetates↗
PubMed1990

Spermine-like functions of N1, N12-bis(ethyl)spermine: stimulation of protein synthesis and cell growth and inhibition of gastric ulceration.

The spermine analogue N1, N12-bis(ethyl)spermine (BESPM) could mimic the functions of spermine in the following aspects: 1) BESPM could stimulate globin and ornithine decarboxylase synthesis in a rabbit reticulocyte cell-free system; 2) the addition of BESPM to the culture medium could recover cell growth of polyamine-deficient bovine lymphocytes; 3) spermidine uptake by bovine lymphocytes was inhibited by BESPM and spermine to a comparable degree; and 4) stress-induced gastric ulceration was inhibited by subcutaneous administration of BESPM. Since BESPM was less toxic than spermine for mice, BESPM or its derivatives may be useful for diseases which can be cured by polyamines.

Animals↗
PubMed1991

A molecular mechanics study of spermine complexation to DNA: a new model for spermine-poly(dG-dC) binding.

Molecular mechanics calculations of the binding of spermine to a number of solvated DNA helices have led to the development of a new model for spermine complexation. The structural details of the complexes formed with d(GCGCGCGCGC)2 and d(ATATATATAT)2 decamers allowed a rationalization of the observed experimental differences for binding to these two helices. For d(ATATATATAT)2 it was concluded that spermine remains in a cross-major groove binding site. Conversely, for d(GCGCGCGCGC)2 spermine reorientation via specific ligand-base-pair hydrogen-bond formation allows complexation along the major groove. The solvent plays an important role in differentiating the two binding modes. A mechanism of spermine complexation to natural DNA is postulated from these results. Past experimental data are also considered in the context of the new model.

Base Sequence↗
PubMed1991

Superoxide dismutase activity regulation by spermine: a new dimension in spermine biochemistry and sperm development.

Amines are a group of highly important compounds of biological importance; they are known promoters of cell growth, can complex with nucleic acids and can stimulate DNA-primed RNA polymerase activity. Spermine, a polyamine abundantly present in the secretions of the male accessory sex organs, has received no functional attributes till date. This study had been a pioneer attempt to validate the hypothesis of a metalloenzyme activity modulation by spermine and implicit correlations have been drawn.

Animals↗
PubMedDate not supplied

Differential effects of the spermine analog, N1, N12-bis(ethyl)-spermine, on polyamine metabolism and cell growth in human melanoma cell lines and melanocytes.

We have previously found that in one of two human melanoma cell lines, potent increase in the polyamine catabolizing enzyme, spermidine/spermine N1-acetyltransferase (SSAT), correlate with growth sensitivity to the spermine analog, N1, N12-bis(ethyl) spermine (BESPM). Herein, we examine the generality of this SSAT response among seven human melanoma cell lines (LOX, SH-1, STO-1, HO, PANUT-3, MALME-3 and Ebey) and normal melanocytes and further evaluate its possible correlation with growth sensitivity. Following treatment with 10 microM BESPM for 48 hr, SSAT activity among the various cell lines increased from basal levels of 20-90 pmol/min/mg to levels ranging from 170 to 30,470 pmol/min/mg. Five of the seven cell lines and melanocytes induced SSAT activity to levels to greater than 2,500 pmol/min/mg and three of these, to levels greater than 10,000 pmol/min/mg. When ranked according to SSAT responsiveness (LOX less than SH-1 less than STO-1 less than HO less than PANUT-3 less than MALME3 less than Ebey), there was a general correlation among the cell lines with growth sensitivity. Antiproliferative effects ranged from slowing of cell growth in the less SSAT responsive lines (LOX, SH-1) to total cessation of cell growth or overt cytotoxicity in the more potently SSAT responsive lines (MALME-3, Ebey). The polyamine biosynthetic enzyme activities, ornithine and S-adenosylmethionine decarboxylase, were similarly suppressed in all cell lines, presumably via analog activation of inherent regulatory mechanisms. Polyamine pool reduction occurred to a greater extent than predicted in cell lines where SSAT was increased to greater than 2500 pmol/min/mg suggesting a possible role for the enzyme in enhancing polyamine excretion and/or catabolism. The occurrence of potent SSAT induction among several human melanoma cell lines and the growth sensitivity of these same lines to BESPM suggests that the enzyme response may represent a determinant of drug action in this particular malignancy.

Acetyltransferases↗
PubMed1991

[Spermine inhibition of in vitro fertilizing ability of human spermatozoa and its possible mode of action].

The direct effect of spermine at various concentrations (0.25-8.0 mmol/L) on in vitro fertilizing ability of human spermatozoa was evaluated by the penetration test of zona-free hamster egg. To study the effect of spermine on capacitation, as judged by the rate of penetration, spermatozoa were incubated in BWW with various concentrations of spermine for 6 h at 37 degrees C. The hyperactivated motility of spermatozoa was markedly inhibited by spermine at a concentration of 4.0 mmol/L. The penetration rate was decreased proportionally to the dose of spermine used. Spermatozoa were incubated in BWW with 0.5 mmol/L spermine for 6 h and another 4 h after spermine was washed off with spermine-free BWW. The percentage of penetration was comparable to that of the control. Therefore, spermine-mediated inhibition of capacitation was reversible. Moreover, exogenous dbcAMP (0.5-1.0 mmol/L) or caffeine (10 mmol/L) could antagonize significantly the spermine-induced inhibition of capacitation with a correlation coefficient of 0.990. The content of spermine in fertile men spermatozoa was assayed by HPLC. Before capacitation spermine in spermatozoa was 7.05 micrograms/10(7) cells, whereas after capacitation it was no longer detectable, indicating that spermine may be an inhibitor of in vitro capacitation in human sperm. To study the effect of spermine on capacitated sperm, spermine was added to the BWW medium after sperm had been preincubated in spermine-free BWW. The persistent presence of spermine could interfere with spermatozoa attachment to, binding to and penetration into zona-free hamster eggs, which was related to the concentration (r = 0.820) used.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Spermine stimulates the threonyl-tRNA formation in rat liver.

The effects of spermine have been studied on the aminoacylation reaction catalyzed by rat liver threonyl-tRNA synthetase. Spermine can not replace Mg2+ in this reaction. However, a stimulatory and synergistic effect was observed on the threonyl-tRNA formation, in the presence of spermine and suboptimal concentration of Mg2+. Other divalent cations like Ba2+, Ca2+, Mn2+ and Co2+ can substitute Mg2+ in the threonyl-tRNA formation, but in all these cases spermine had no significant effect. Spermine prevented the inhibitory effects caused by excess of ATP or tRNA on the aminoacylation reaction. Association constants were determined by equilibrium dialysis for the tRNA-spermine complex (Ka = 3.7 x 10(3) M-1) and by differential spectrophotometry for the ATP-spermine complex (Ka = 7.8 x 10(3) M-1). No enzyme-spermine complex could be detected by equilibrium dialysis. Some roles have been ascribed for the polyamine spermine in the stimulation of the threonyl-tRNA formation. ATP-spermine and tRNA-spermine can not function as substrates for the threonyl-tRNA synthetase, since Mg2+ is indispensable. The stimulatory effect by spermine is important considering the physiological concentration of Mg2+ in the tissues. Probably in vivo spermine would have a relevant role lowering the real Mg2+ concentration required in the aminoacylation reaction.

Adenosine Triphosphate↗
PubMed1990

Responsibility of tRNA(Ile) for spermine stimulation of rat liver Ile-tRNA formation.

To determine whether tRNA or aminoacyl-tRNA synthetase is responsible for spermine stimulation of rat liver Ile-tRNA formation, homologous and heterologous Ile-tRNA formations were carried out with Escherichia coli and rat liver tRNA(Ile) and their respective purified Ile-tRNA synthetases. Spermine stimulation was observed only when tRNA from the rat liver was used. Spermine bound to rat liver tRNA(Ile) but not to the purified aminoacyl-tRNA synthetase complex. Kinetic analysis of Ile-tRNA formation revealed that spermine increased the Vmax and Km values for rat liver tRNA(Ile). The Km value for ATP and isoleucine did not change significantly in the presence of spermine. Furthermore, higher concentrations of rat liver tRNA(Ile) tended to inhibit Ile-tRNA formation if spermine was absent. Spermine restored isoleucine-dependent PPi-ATP exchange in the presence of rat liver tRNA(Ile), an inhibitor of this exchange. The nucleotide sequence of rat liver tRNA(Ile) was determined and compared with that of E. coli tRNA(Ile). Differences in nucleotide sequences of the two tRNAs(Ile) were observed mainly in the acceptor and anticodon stems. Limited ribonuclease V1 digestion of the 3'-32P-labeled rat liver tRNA(Ile) showed that both the anticodon and acceptor stems were structurally changed by spermine, and that the structural change by spermine was different from that by Mg2+. The influence of spermine on the ribonuclease V1 digestion of E. coli tRNA(Ile) was different from that of rat liver tRNA(Ile). The results suggest that the interaction of spermine with the acceptor and anticodon stems may be important for spermine stimulation of rat liver Ile-tRNA formation.

Amino Acyl-tRNA Synthetases↗
PubMed1979

Effects of spermine on the detection of induced forward mutation at the Can1 locus in yeast: evidence for selection against canavanine-resistant mutants.

The effect of exogenous spermine tetrahydrochloride (0.5 mg/ml) on hydrazine- and nitrous acid-induced forward mutation to canavanine resistance (CAN1 leads to can1, normal to defective arginine permease) was examined in stationary-phase haploid Saccharomyces cerevisiae. Post-treatment cell division (specifically DNA replication) is required for hydrazine mutagenesis at this locus, whereas nitrous acid mutagenesis exhibits, in addition, a significant post-treatment-independent component. Spermine addition only during mutagenic treatments in buffer did not affect mutagen cytotoxicity, but did result in a slight yet consistent decrease in induced mutation frequencies. Addition of spermine to the yeast extract--peptone--dextrose (YEPD) post-treatment growth medium resulted in dramatic reductions of induced mutation frequencies, which could be alleviated by pregrowth in spermine-containing YEPD. Such a medium was found to cause an apparent temporary growth inhibition for almost 40 h, after which the growth rate of the culture increased rapidly. Cultures "recovering" from spermine inhibition were no longer inhibitable by spermine in fresh medium, suggesting an outgrowth of spontaneous and/or induced spermine-resistant derivatives. Genetic analysis of one isolate revealed a single dominant nuclear gene conferring resistance by some means other than defective spermine uptake. Growth of this mutant was only slightly inhibited by spermine (20% increase in doubling time), while mutation expression remained high. Results of competitive growth experiments indicated that spermine-containing YEPD exerted a selection pressure against canavanine-resistant cells, while YEPD by itself did not. The mechanism for this selection is not presently understood. With respect to replication-dependent induced mutation at CAN1, our initial observation of a strong apparent antimutagenic action of spermine was found to be best explained by this specific selection against can1 mutants. This underscores the need for caution in the interpretation of experiments designed to study physiological modification of mutagenic potential.

Canavanine↗
PubMed1991

Spermine: an anti-oxidant and anti-inflammatory agent.

This work demonstrates that spermine is a natural antioxidant and anti-inflammatory agent. It is found that: (1) Spermine inhibits the cytochrome C reduction initiated by FMLP- or PMA-stimulated human granulocytes. (2) Spermine inhibits the Fe(III)/xanthine oxidase stimulated lipid peroxidation of brain phospholipid liposomes. The antioxidative effect disappears at high Fe(III) concentrations. (3) Spermine forms a complex with Fe(II). (4) Spermine inhibits the Fe(II)-induced depolymerization of hyaluronic acid, and EDTA abolishes this effect. (5) Spermine or spermine-Fe(II) has no superoxide mimetic effect. These findings suggest that spermine has at least two antioxidative mechanisms of action: (I) Spermine inhibits the generation of the transport of superoxide radicals from stimulated granulocytes, and (II) Spermine inhibits the Haber-Weiss reaction by forming an unreactive chelate with Fe. Spermine thus prevents generation of destructive hydroxyl radicals.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1990

Reversibility of spermine-induced intestinal maturation in the rat.

In the present investigation, the reversibility of spermine-induced precocious intestinal maturation was studied. Neonatal rats received either saline or spermine (4 mumol, twice daily) solution orally on the 11th and 12th postnatal day. They were killed on the 13th, 14th, 15th, 16th, and 17th postnatal days. After the small bowel was removed, it was either divided into three equal parts or prepared for electrophoretic analysis. Histological examination, protein content measurement, and disaccharidase activity estimation were performed on each part of the intestine. Spermine administration was shown to induce structural and mucosal enzyme changes characteristic of postnatal maturation. This phenomenon, which was generally clearly observed in 13- and 14-day-old rats, then became less apparent in 15- and 16-day-old animals. Differences were noted according to the segment of intestine or the biochemical parameter analyzed. When rats were 17 days old, no significant differences generally existed between control and spermine-treated rats. If the 140- to 150-kDa proteins, isolated by electrophoresis, are assumed to represent the subunits of the sucrase-isomaltase complex, the results obtained indicate that spermine induces a modification of the concentration of this complex. When compared to values obtained in adult rats, the concentration of the complex was approximately three times higher in spermine-treated 13-day-old rats, while no differences were found in spermine-treated 14-day-old rats. Further, similar concentrations were found in control and spermine-treated rats with an age of 17 days. These results suggest that spermine-induced precocious intestinal maturation is reversible when spermine treatment is stopped.

Animals↗
PubMed1989

Efficacy and toxicity of N,N',N",N"'-tetra(2,3,4-trihydroxybenzoyl)-spermine for decorporation of 239Pu from mice.

Male SAS/4 mice were injected i.v. with 6.6 kBq 239Pu-citrate. After 1 or 24 h a single i.p. injection of 15 or 30 mumol kg-1 or repeated (three or four) daily injections of 30 mumol kg-1 of tetra-THB-spermine were given, and at 4 or 7 days Pu retention was measured in liver, kidneys and femur. Besides tetra-THB-spermine, equimolar doses of tetra-DHB-spermine were injected for comparison, or equimolar doses of diethylene triamine-pentaacetic acid (DTPA) as a reference compound. Histological changes in kidneys and liver were examined after i.p. injections of 30 mumol kg-1 or at 2-13 times higher doses of tetra-THB-spermine. The results show that: (1) Introduction of an additional hydroxy group into the aromatic moieties of tetra-DHB-spermine results in increased hydrophilicity, lower toxicity and a lower renal retention of Pu. (2) Tetra-THB-spermine and tetra-DHB-spermine are similarly effective in removing plutonium from liver and bone. Their efficacies in removing Pu from bone are approximately similar to those of DTPA but for whole-body removal they are generally inferior. (3) Multiple (30 mumol kg-1) of tetra-THB-spermine were no more effective than a single injection at mobilizing Pu from the liver. (4) Four injections of tetra-THB-spermine induced cloudy swelling and fatty degeneration in epithelial cells of the proximal convoluted tubules. At levels of 400 mumol kg-1 tetra-THB-spermine produced severe degenerative glomerular lesions, foci of liver necrosis and thromboses of the portal vein branch.

Animals↗
PubMed1989

Molecular dynamics of spermine-DNA interactions: sequence specificity and DNA bending for a simple ligand.

We used molecular dynamics to model interactions between the physiologically important polyamine spermine and two B-DNA oligomers, the homopolymer (dG)10-(dC)10 and the heteropolymer (dGdC)5-(dGdC)5. Water and counterions were included in the simulation. Starting coordinates for spermine-DNA complexes were structures obtained by molecular mechanics modeling of spermine with the two oligomers; in these models, spermine binding induced a bend in the heteropolymer but not in the homopolymer. During approximately 40 psec of molecular dynamics simulation, spermine moves away from the floor of the major groove and interacts nospecifically with d(G)10-d(C)10. In contrast, a spermine-induced bend in the helix of (dGdC)5-(dGdC)5 is maintained throughout the simulation and spermine remains closely associated with the major groove. These results provide further evidence that the binding of spermine to nucleic acids can be sequence specific and that bending of alternating purine-pyrimidine sequences may be a physiologically important result of spermine binding.

Base Sequence↗
PubMed1977

Specific effects of spermine on ouabain-sensitive and potassium-dependent phosphatase activity of kidney plasma membranes. Specificity of the potassium sites.

Specific inhibition of ouabain-sensitive and K+-dependent p-nitrophenyl-phosphatase activity of rabbit kidney plasma membranes by spermine (N,N'-bis(3-aminopropyl)-1,4-butanediamine) was characterized kinetically. 1. Inhibition by spermine was competitive with K+. The Ki for spermine was 31 micronM in the presence of 1 mM Mg2+. 2. Excess Mg2+ inhibited the ouabain-sensitive phosphatase activity in competition with K+. The Ki for Mg2+ was 2.6 mM. 3. Increasing Mg2+ concentrations reduced the spermine inhibition. This could be observed at Mg2+ concentrations higher than that of K+. 4. In the absence of inhibition by Mg2+, spermine was noncompetitive with Mg2+ which was essential for the ouabain-sensitive phosphatase activity. This could be observed at Mg2+ concentrations lower than that of K+. 5. Although Ca2+ was a strong inhibitor of the ouabain-sensitive phosphatase activity in the presence of K+, it produced a small stimulation of the activity in the absence of K+. Approximately 0.1 mM Ca2+ gave the maximum stimulation. 6. The observed Ca2+- and Mg2+-dependent phosphatase activity was inhibited strongly by ouabain and by spermine. The half-maximal inhibition concentrations of ouabain and spermine were 0.1 and 63 micronM, respectively. It is likely that Mg2+, Ca2+ and spermine bind to the same site as does K+.

4-Nitrophenylphosphatase↗