Disease relevance of St8sia1

• GD3 synthase gene knockout mice exhibit thermal hyperalgesia and mechanical allodynia but decreased response to formalin-induced prolonged noxious stimulation [1].
• Thus, the high GD2:GD3 ratios characteristic of most neuroblastomas result from low levels of GD3 synthase as well as high levels of GD2 synthase [2].
• These results demonstrate that suppression of GD3-synthase expression, which results primarily in a marked decrease in the concentration of ganglioside GD3, greatly reduces cell spreading, invasion and both the incidence and growth rate of experimental metastasis of F-11 cells [3].

High impact information on St8sia1

• In our previous study (G. Zeng et al., Biochemistry, 38: 8762-8769, 1999), we established a subclone of the rat dorsal root ganglion-derived F-11 cells in which the expression of ganglioside GD3 was inhibited by stable transfection of the antisense vector against CMP-NeuAc: GM3 alpha2-8 sialyltransferase (GD3-synthase) gene [4].
• Therefore, our results demonstrate that reduced tumor growth in nude mice by suppression of GD3-synthase expression in F-11 cells results from minimal angiogenesis of the tumors through down-regulation of the VEGF expression, which indicates an important role for GD3 in tumor angiogenesis [4].
• For example, in cell lines containing high amounts of GD2 ganglioside, the level of the preceding enzyme in the pathway (GD3 synthase) was unexpectedly low [2].
• Results of the present study indicate that AGEs caused an inhibition of both bovine retinal pericyte (BRP) and rat renal mesangial cell (RMC) proliferation, associated with an increase of a-series gangliosides consecutive to GM3 synthase activity increase and GD3 synthase activity inhibition [5].
• Furthermore, GD3 synthase gene expression strongly decreased MMP-9 promoter activity in response to TNF-alpha [6].

Biological context of St8sia1

• Transfection of the protein A-fused ST8Sia III gene into COS-7 cells led to alpha 2,8-sialyltransferase activity toward sialylated glycoproteins and alpha 2,3-sialylated glycosphingolipids, such as alpha 2,3-sialylparagloboside and GM3 [7].
• The predicted amino acid sequence of ST8Sia IV showed 15.2, 56.0, and 26% identity with those of so far cloned mouse alpha2,8-sialytransferases, i.e. GD3 synthase (ST8Sia I), STX(ST8Sia II), and Sia(alpha)2,3Galbeta1,4GlcNAc(alpha)2,8-sialyl-transferase (ST8Sia III) [8].
• We generated double knock-out mice lacking the GM2/GD2 and the GD3 synthase gene by mating single gene mutants, and we analyzed the abnormal phenotypes of the mutant mice expressing only the GM3 ganglioside [9].
• A cDNA clone of GD3 synthase, pD3T-31 was co-transfected with a cDNA library prepared from rat brain RNA using the pcDNAI expression vector [10].
• When brain tissue was analyzed as a whole mass, a typical pattern corresponding to the reported findings obtained by biochemical analyses was observed, i.e., high expression of GD3 synthase gene in the early stage and gradual increase of GM2/GD2 synthase gene expression in the late stage of the development [11].

Anatomical context of St8sia1

• Co-transfection of the cell line with pM1T-9 and a GD3 synthase cDNA resulted in the expression of GD1b as well as GM1 [10].
• The mouse Sia alpha 2,3Gal beta 1, 4GalNAc alpha 2,8-sialyltransferase (ST8Sia III) genomic gene, whose transcripts are only expressed in fetal and newborn brain and testis, was isolated and its 5'-flanking region was analyzed [12].
• However, on treatment with DMSO, which induces muscle cells, there was no change in the level of GD3 synthase activity, and its transcript was hardly detected during the course of muscle differentiation [13].
• These results indicate that the GD3 synthase gene may be involved in early tooth development, particularly in the proliferation of dental epithelium [14].
• In addition, dental epithelial cells transiently transfected with the GD3 synthase gene showed enhanced proliferation [14].

Associations of St8sia1 with chemical compounds

• On the other hand, the level of GQ1b synthase (alpha 2,8-sialyltransferase, SAT-V) in RA-induced aggregates was significantly higher than that in neurons [13].
• The cells that expressed GD3 were established from Neuro2a cells by transfection of a mammalian expression vector into which were carried a cDNA encoding GD3 synthase and the blasticidin-S-deaminase gene with a SV40 promoter, followed by selection with blasticidin-S-hydrochloride [15].
• In addition, N2a-GD3 expressed acetylcholine esterase, indicating that the differentiation of Neuro2a cells was induced by expression of GD3 synthase and subsequent modification of the biosynthesis and expression of gangliosides [15].
• In a search for the genes involved in this ganglioside-induced Neuro2a differentiation, we used a tetracycline-regulated GD3 synthase cDNA expression system combined with differential display PCRs to identify mRNAs that were differentially expressed at four representative time points during the process [16].
• Optimum GD3 synthase activity was obtained at pH 6.0 using 0.1% detergent Triton CF-54 [17].

Regulatory relationships of St8sia1

• Addition of neutralizing anti-Fas-L antibodies reduced the extent of 'low-K+'-induced apoptosis and abolished the increase in GD3 levels and GD3 synthase mRNA [18].

Other interactions of St8sia1

• To further restrict the expression of gangliosides, the GD3S mutant mice were crossbred with mice carrying a disrupted GalNAcT gene encoding beta1,4-N-acetylgalactosaminyltransferase [19].
• The sequence of ST8Sia VI encodes a protein of 398 amino acids and shows 42.0 and 38.3% amino acid sequence identities to mouse alpha2,8-sialyltransferases ST8Sia I (GD3 synthase) and ST8Sia V (GD1c, GT1a, GQ1b, and GT3 synthases), respectively [20].
• We have disrupted the gene encoding GD3 synthase (GD3S), a sialyltransferase expressed in the CNS that is responsible for the synthesis of b-series gangliosides [19].
• GM2/GD2 synthase and GD3 synthase are key enzymes for ganglioside synthesis, because their relative activities regulate the main profiles of ganglioside expression [11].
• Degenerating granule cells showed increased expression of both Fas receptor and its ligand (Fas-L), at times that coincided with the increase in GD3 levels and the induction of GD3 synthase mRNA [18].

Analytical, diagnostic and therapeutic context of St8sia1

• Molecular cloning of Sia alpha 2,3Gal beta 1,4GlcNAc alpha 2,8-sialyltransferase from mouse brain [7].
• Mouse GD3 synthase (EC 2.4.99.8) cDNA was cloned by eukaryotic expression cloning, and its mRNA expression as well as that of GM2/GD2 synthase gene during the development of the mouse CNS was analyzed by using northern blotting, reverse transcription-polymerase chain reaction, and in situ hybridization [11].
• The chromosomal location of the GD3 synthase gene (SIAT8) was determined in human and mouse using fluorescence in situ hybridization and interspecific backcross analysis, respectively [21].
• The complete nucleotide sequence of the cDNA coding for rat GD3-synthase was determined for the first time using PCR and the rapid amplification of cDNA ends (RACE) procedures [22].
• We analyzed the expression of the GD3 synthase gene in laser-dissected teeth germs using RT-PCR [14].

References