Disease relevance of Sms

• In summary, the Gy mutation is associated with a recessively expressed mutation of the spermine synthase gene, leading to spermine deficiency, and a dominantly expressed mutation of the Pex gene, leading to hypophosphatemia [1].
• PURPOSE: To investigate the hypothesis that modulation of the function of activated macrophages is one of the mechanisms of the clinically observed anti-inflammatory and analgesic efficacy of low-dose radiotherapy in the treatment of a variety of painful joint diseases with total doses between 1 and 6 Gy [2].

High impact information on Sms

• Uridine had no effect on the apoptosis initiated by 1 Gy of gamma-radiation [3].
• Specifically, a low dose of ionizing radiation (3 Gy) induces phosphorylation of Akt at Ser473 in the vascular endothelium within minutes of irradiation [4].
• Inhibition of tumor growth is correlated with spermidine depletion and an increase of decarboxylated-S-adenosylmethionine, the aminopropyl donor in the spermidine and spermine synthase reactions [5].
• It was not clear to what extent these alterations were due to the loss of spermine synthase activity, since this chromosomal deletion extends well beyond the SpmS gene and includes at least one other gene termed Phex [6].
• The resulting Gy-CAG/SpmS mice had extremely high levels of spermine synthase and contained spermine in all tissues examined [6].

Biological context of Sms

• A pseudogene for spermine synthase was also identified in the mouse genome [1].
• Spermine is formed from spermidine by the action of spermine synthase, an aminopropyltransferase, whose gene (SpmS) is located on the X chromosome [6].
• NOS1-/- cells showed a prolonged G1 cell cycle arrest after 10 Gy [7].
• MATERIALS AND METHODS: Metabolic activity, cell proliferation, reproductive integrity, nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression by unstimulated or [LPS/gamma-IFN-stimulated macrophages in vitro was investigated at different times after radiation doses ranging from 0.3 Gy to 10 Gy [2].
• Inhibition of cell growth by combination of alpha-difluoromethylornithine and an inhibitor of spermine synthase [8].

Anatomical context of Sms

• With the use of homologous recombination technique, we disrupted the gene encoding spermine synthase in mouse embryonic stem cells [9].
• Effect of spermine synthase deficiency on polyamine biosynthesis and content in mice and embryonic fibroblasts, and the sensitivity of fibroblasts to 1,3-bis-(2-chloroethyl)-N-nitrosourea [10].
• I(K1)and I(to)currents were also studied in myocytes from mutant Gyro (Gy) mice in which the spermine synthase gene is disrupted, leading to a complete loss of spermine [11].
• The functional changes in macrophages (Mphi) following exposure to a high dose (6 Gy) of gamma-rays in vitro were investigated [12].
• 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 [13].

Associations of Sms with chemical compounds

• Effect of S-adenosyl-1,12-diamino-3-thio-9-azadodecane, a multisubstrate adduct inhibitor of spermine synthase, on polyamine metabolism in mammalian cells [14].
• It was found that N-(3-aminopropyl)-1,4-diamino-cis-but-2-ene [the cis isomer of the alkene analogue of spermidine] was a good substrate for spermine synthase, but that the trans isomer [N-(3-aminopropyl)-1,4-diamino-trans-but-2-ene] and the alkene analogue [N-(3-aminopropyl)-1,4-diaminobut-2-yne] were not substrates [15].
• 2. Ascites-tumour cells likewise exhibited high activities of L-ornithine decarboxylase (EC 4.1.1.17), S-adenosyl-L-methionine decarboxylase (EC 4.1.1.50), spermidine synthase (EC 2.5.1.16) and spermine synthase [16].
• Consistent with these observations, 17beta-oestradiol-treated tumours were less radio-responsive compared to control tumours when treated with a single radiation dose of 15 Gy [17].
• Mammalian spermine synthase activity was strongly inhibited by S-methyl-5'-methylthioadenosine [18].

Other interactions of Sms

• Effect of polyamine depletion on caspase activation: a study with spermine synthase-deficient cells [19].
• 1. Injection of 2,2-difluoroputrescine (DFPut) into the yolk sac of chick embryos causes the formation of 6,6-difluorospermidine (6,6DFSpd) and 6,6-difluorospermine (6,6DFSpm), demonstrating that the difluoroanalogs of putrescine and spermidine are in vivo substrates of spermidine and spermine synthase, respectively [20].

Analytical, diagnostic and therapeutic context of Sms

• Reverse transcription-polymerase chain reaction and immunofluorescence analysis of D2XRII murine bone marrow stromal cells showed that gamma irradiation with doses of 2-50 Gy from (137)Cs stimulated expression of nitric oxide synthase 2 (Nos2, also known as iNos) [21].
• The thorax of BALBc mice were exposed to 14 Gy radiation (experimental) or no radiation (control) and killed after at 1, 3, 6, 12, and 24 hours; 3, 15, and 30 days; and 3 and 6 months after treatment [22].

References