Disease relevance of St8sia2

• To investigate which of two PSA synthase (ST8Sia II and IV) are involved in the biosynthesis of PSA associated with NCAM, the expressions of PSA, PSA synthase activity, and the genes of two PSA synthases during in vitro neuronal differentiation of mouse embryonal carcinoma P19 cells were determined [1].
• Two polysialic acid synthases, mouse ST8Sia II and IV, synthesize different degrees of polysialic acids on different substrate glycoproteins in mouse neuroblastoma Neuro2a cells [2].
• Taken together, our findings indicate that this SUPER TWIG is therapeutic agent against infections by Stx-producing E. coli [3].
• Ovarian disease was not found in D7TX or STX mice [4].
• Gastritis developed in both female (57%) and male (50%) BALB/cBy mice after D3TX, occasionally after D7TX, but not after STX [4].

High impact information on St8sia2

• Enterohemorrhagic Escherichia coli (EHEC) 0157:H7 is a food-borne pathogen that can cause bloody diarrhea and, occasionally, acute renal failure as a consequence of Shiga toxin (Stx) production by the organism [5].
• Here we developed a series of carbosilane dendrimers, in which trisaccharides of globotriaosyl ceramide, a receptor for Stx, were variously oriented at their termini (referred to as SUPER TWIG), and identified a SUPER TWIG with six trisaccharides as a Stx neutralizer functioning in the circulation [3].
• The SUPER TWIG neutralized Stx in vivo by a mechanism in which the accumulation and immediate degradation of Stx by phagocytic macrophages present in the reticuloendothelial system were induced [3].
• Measurements of [(3)H]saxitoxin (STX) binding showed a significant reduction in the level of plasma membrane sodium channels in beta2(-/-) neurons [6].
• The synthesis of this unique carbohydrate polymer depends on the polysialyltransferases ST8SiaII and ST8SiaIV [7].

Chemical compound and disease context of St8sia2

• Ciprofloxacin but not fosfomycin causes Shiga toxin-encoding bacteriophage induction and enhanced Shiga toxin (Stx) production from E. coli O157:H7 in vitro [8].
• Daisy also protected streptomycin-treated mice from Escherichia coli O91:H21 and did not interfere with the ability of the murine immune system to produce Stx-specific protective antibodies [9].
• Azithromycin exhibited strong in vitro activity against STEC without inducing Stx-converting phage, in marked contrast to norfloxacin [10].
• It has been suggested that Shiga toxin (Stx) is necessary but not sufficient for hemolytic uremic syndrome (HUS) development, and pro-inflammatory stimuli such as lipopolysaccharide (LPS) from Gram negative bacteria are needed [11].
• Because cytokines, in particular TNF-alpha, contribute to the pathologic process in Stx-producing Escherichia coli (STEC) infection, this study suggested that anisodamine could be a potential drug for treatment of STEC infection [12].

Biological context of St8sia2

• Similar up-regulation of the ST8Sia II gene were observed during the differentiation of rat MNS-8 cells, which were derived from E-12 rat neuroepithelium of the neural tube and shown to differentiate into neurons [1].
• PSA synthase activity was not detected in undifferentiated or aggregated P19 cells, it increasing in parallel with ST8Sia II gene expression during differentiation [1].
• To verify the physiological relevance of identified mutations, identical amino acid substitutions were introduced into epitope-tagged variants of hamster ST8SiaIV and murine ST8SiaII and recombinant proteins were tested in vivo and in vitro [13].
• In the mammalian genome, two polysialyltransferases termed ST8Sia-II and ST8Sia-IV have been hypothesized to be responsible for the production of PSA in vivo [14].
• Genomic structure and promoter activity of the mouse polysialic acid synthase gene (mST8Sia II). Brain-specific expression from a TATA-less GC-rich sequence [15].

Anatomical context of St8sia2

• In further contrast with ST8Sia-IV deficiency, loss of ST8Sia-II did not impair hippocampal synaptic plasticity but instead resulted in the misguidance of infrapyramidal mossy fibers and the formation of ectopic synapses in the hippocampus [14].
• Polysialic acid synthase (ST8Sia II/STX) mRNA expression in the developing mouse central nervous system [16].
• The distribution of ST8Sia II mRNA in the neocortex and cerebellum coincided with the immunohistochemical localization of PSA [16].
• In this study, we examined the expression of PSA as well as 2 polysialyltransferases, PST and STX, in various tumor cell lines [17].
• Transfection of ST8Sia II gene into several cell lines including NIH3T3 led to the expression of polysialic acids on the cell surface [18].

Associations of St8sia2 with chemical compounds

• N-Glycanase treatment and linkage-specific sialidase treatment of glycoproteins revealed that STX transfers sialic acids through alpha 2,8-linkages to only N-linked oligosaccharides of glycoproteins [19].
• Phosphorylation of tyrosine residues of proteins in the DIM fraction increased by 10 min and returned to the resting level by 30 min after the addition of Stx [20].
• To study the early signal transduction after Stx addition, Gb3-enriched microdomains were prepared from ACHN cells by sucrose density gradient centrifugation of Triton X-100 lysate as buoyant, detergent-insoluble microdomains (DIM) [20].
• However, animals treated with ciprofloxacin had a marked increase in free fecal Stx, associated with death in two-thirds of the mice, whereas fosfomycin did not [8].
• The data suggest that azithromycin (at least at higher concentrations) has a strong effect on Stx production by STEC and on the Stx-induced inflammatory host response and prevents death in mice [10].

Other interactions of St8sia2

• These results indicate that ST8Sia II predominantly directs PSA expression during neuronal differentiation rather than ST8Sia IV [1].
• Enzymatic activity of a developmentally regulated member of the sialyltransferase family (STX): evidence for alpha 2,8-sialyltransferase activity toward N-linked oligosaccharides [19].

Analytical, diagnostic and therapeutic context of St8sia2

• Consistent with studies of animal models bearing these morphological changes, ST8Sia-II-deficient mice exhibited higher exploratory drive and reduced behavioral responses to Pavlovian fear conditioning [14].
• Comparison between ST8Sia II and IV mRNA expression was also undertaken by northern blot analysis and competitive PCR analysis [16].
• The MIST Alert for PSP also detected the majority of extracts containing PSP toxin greater than 32 microg STX equiv./100 g, which is the mouse bioassay detection limit [21].
• The HPLC profile showed no traces of TTX, but only the presence of PSPs (STX, GTX 2 and GTX 3) [22].
• Detection of Stx binding to renal sections and apoptotic cells were performed using mouse monoclonal anti-Stx 2 antibody and the TUNEL method, respectively [23].

References