Disease relevance of spermidine

• Gentle lysis of E. coli cells in the presence of a DNA counterion (either 1.0 M NaCl or 5 mM spermidine) permits the isolation of the folded intact bacterial chromosome associated with membrane fragments [1].
• Spermidine nitrosation and gastric cancer [2].
• However, the specific mechanisms responsible for the increased paraquat toxicity in the spermidine-deficient mutants remain to be determined [3].
• The spermidine present in purified virus is associated with viral RNA at the time of packaging and formation of intact virions [4].
• Spermidine, an intrinsic component of turnip yellow mosaic virus [4].

Psychiatry related information on spermidine

• In Alzheimer's disease, arcaine inhibition of [3H]dizocilpine binding (in both the absence and the presence of spermidine) was not different from control in either of the two brain areas examined [5].
• METHOD: 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 [6].
• The affected males have mild-to-moderate mental retardation (MR), hypotonia, cerebellar circuitry dysfunction, facial asymmetry, thin habitus, osteoporosis, kyphoscoliosis, decreased activity of SMS, correspondingly low levels of intracellular spermine in lymphocytes and fibroblasts, and elevated spermidine/spermine ratios [7].
• In the present study, we investigated the effect of immediate post-training bilateral infusion of spermidine, a polyamine agonist, into the amygdala on inhibitory avoidance learning of rats [8].
• Pretreatment with 80 mg/kg but not 15 or 40 mg/kg spermidine (i.p.) before dizocilpine impaired maze learning compared to saline controls [9].

High impact information on spermidine

• In vitro experiments with a fusion construct using reticulocyte lysates demonstrate polyamine-dependent expression with a frameshift efficiency of 19% at the optimal concentration of spermidine [10].
• The RNA moieties of ribonuclease P purified from both E. coli (M1 RNA) and B. subtilis (P-RNA) can cleave tRNA precursor molecules in buffers containing either 60 mM Mg2+ or 10 mM Mg2+ plus 1 mM spermidine [11].
• Transglutaminase was effective in promoting the binding of spermidine to the sperm [12].
• Three of the six spermidine homologs supported cell growth during a 48-hour incubation in the presence of DFMO, indicating that a two-carbon extension of spermidine structure was tolerated for biological function [13].
• No more than 15 percent of the spermidine normally present in L1210 cells was required for cell proliferation in the presence of DFMO [13].

Chemical compound and disease context of spermidine

• The spermidine contents of numerous virus preparations were in the range 200-700 molecules per virion and were considerably in excess of those of spermine [4].
• Although not highly significant, spermidine concentrations were elevated slightly in benign hyperplasia, whereas the putrescine content was decreased compared to normal tissue [14].
• At 1 mug/ml at 37 degrees, the naturally occurring spermidine derivative of bleomycin (A5) was far more lethal to Escherichia coli than were several other bleomycins tested [15].
• These changes are similar to previously reported changes in the spermidine concentration in sera and in tumors following the administration of a single dose of 5-fluorouracil to rats with 3924A hepatomas [16].
• Escherichia coli mutants completely deficient in adenosylmethionine decarboxylase and in spermidine biosynthesis [17].

Biological context of spermidine

• Polyamines putrescine, spermidine, and spermine specifically inhibit the PK 380--catalyzed phosphorylation of eukaryotic initiation factor 2 alpha (eIF-2 alpha) [18].
• These results suggest that the uranyl, hexamminecobalt (III) and spermidine ions compete for the same high affinity binding site on the junction [19].
• Absolute requirement of spermidine for growth and cell cycle progression of fission yeast (Schizosaccharomyces pombe) [20].
• CPENSpm treatment results in the superinduction of the polyamine catabolic enzyme spermidine/spermine N1-acetyltransferase (SSAT) in sensitive cell types and has been demonstrated to induce programmed cell death (PCD) [21].
• Treatment of the linear, ligated plasmid with spermidine results in formation of condensates that were detected by light scattering and observed by transmission electron microscopy [22].

Anatomical context of spermidine

• Spermidine requirement for cell proliferation in eukaryotic cells: structural specificity and quantitation [13].
• This rise is prevented by exogenous spermidine but only in the presence of monocytes [23].
• CONCLUSIONS: Spermidine or spermine is essential for hepatocyte growth factor-induced DNA synthesis in primary cultured rat hepatocytes [24].
• Identification of hypusine, an unusual amino acid, in a protein from human lymphocytes and of spermidine as its biosynthetic precursor [25].
• On further incubation in the spermidine-deprived medium, growth occurs in most of the cells, not by cell division but rather by cell elongation, with an abnormal distribution of the actin cytoskeleton, DNA (4', 6-diamidino-2-phenylindole staining), and calcofluor-staining moieties [20].

Associations of spermidine with other chemical compounds

• Lactase, sucrase, and maltase specific activities (micromoles of substrate hydrolyzed per minute per gram of protein) were 80 +/- 10, 10 +/- 3, and 116 +/- 19 for the saline-treated rats; 51 +/- 7, 34 +/- 2, and 315 +/- 37 for the spermidine-treated rats; and 25 +/- 2, 46 +/- 5, and 419 +/- 63 for the spermine-treated rats, respectively [26].
• Increases in the activity of S-adenosylmethionine decarboxylase and the content of spermidine were observed 33-37 hr after administration of galactosamine [27].
• Schizosaccharomyces pombe cells that cannot synthesize spermidine or spermine because of a deletion-insertion in the gene coding for S-adenosylmethionine decarboxylase (Deltaspe2) have an absolute requirement for spermidine for growth [20].
• The naturally occurring organic polycations such as spermine and spermidine inhibit histamine-stimulated gastric acid secretion by bullfrog gastric mucosa in vitro; spermine is much more potent than spermidine [28].
• A cluster of basic residues in glutathione reductase is replaced by neutral, hydrophobic, or acidic residues in trypanothione reductase, consistent with the nature of the spermidine linkage and the change in overall charge of the substrate from -2 to +1, respectively [29].

Gene context of spermidine

• The conversion of putrescine to spermidine in the biosynthetic pathway of plant polyamines is catalyzed by two closely related spermidine synthases, SPDS1 and SPDS2, in Arabidopsis [30].
• These results indicate that S. cerevisiae contains an antizyme-like mechanism for the control of the level of ornithine decarboxylase by spermidine, even though, as contrasted with other eukaryotic cells, no specific antizyme homologue has been detected either in in vitro experiments or in the S. cerevisiae genome [31].
• The polyamine requirement for the growth of this double mutant could only be satisfied by spermidine; i.e., spermine was not effective because it cannot be oxidized to spermidine in the absence of the FMS1 gene [32].
• In both MEU1(+) and the meu1Delta cultures, the ODC levels were markedly decreased by the addition of spermidine to the media, and thus our results contradict the postulation of Subhi et al [33].
• Transformation of stk2::lacZ cells with the STK2 gene cloned into a single-copy expression vector restored spermidine transport to wild-type levels [34].

Analytical, diagnostic and therapeutic context of spermidine

• High-performance liquid chromatography and competition studies with spermidine indicated that the homologs, which vary in the length of the carbon chain separating the amines, penetrated the cells [13].
• The spermine/spermidine N(1)-acetyltransferase gene (SSAT) was successfully validated by reverse transcription-polymerase chain reaction, immunohistochemistry, and Western blot analyses [35].
• The major polyamine of turnip yellow mosaic virus has been identified as spermidine by gas chromatography and mass spectrometry of the trifluoroacetamido derivative [4].
• Under conditions of the precipitation or purification from juice by differential centrifugation, only small amounts of exogenous radioactive spermidine and spermine became bound to virus [4].
• Crystallization of virus in 40% saturated MgSO4 or 7.5% heparin or dialysis did not decrease viral spermidine [4].

References