Disease relevance of STX2

• The virulence genes selected for each category were Stx1, Stx2, and eaeA for enterohemorrhagic E. coli (EHEC), eaeA for enteropathogenic E. coli (EPEC), STIb and LTI for enterotoxigenic E. coli (ETEC), ipaH for enteroinvasive E. coli (EIEC) and Shigella spp., and aggR for enteroaggregative E. coli (EAEC) [1].
• Epimorphin expression in interstitial pneumonia [2].
• These findings suggest that epimorphin contributes to repair of pulmonary fibrosis in nonspecific interstitial pneumonia, perhaps partly by inducing expression of matrix metalloproteinase 2, which is an important proteolytic factor in lung remodeling [2].
• Structure of shiga toxin type 2 (Stx2) from Escherichia coli O157:H7 [3].
• Any of these structural differences might result in different mechanisms of action of the two toxins and the development of hemolytic uremic syndrome upon exposure to Stx2 [3].

Psychiatry related information on STX2

• A 'short family therapy' in schizophrenia, according to a specific systemic model (the 'Elementary Pragmatic Model' or EPM) with a strong paradoxical structure is presented [4].
• With regard to all measures (number of drop-outs, symptoms according to the Brief Psychiatric Rating Scale, social activity according to the Strauss-Carpenter Outcome Scale and an interactive test) the EPM group showed better results [4].
• Although standard EEG rarely demonstrates characteristic changes that may help differentiate causes of dementia, CEEG/EPM appears to demonstrate, on occasion, abnormalities in the posterior temporal and parietal regions in patients with a diagnosis of probable Alzheimer's disease and rarely in other forms of dementia or depression [5].
• In CEEG/EPM studies, a pattern of relative suppression of alpha activity or suppressed auditory P300 amplitude in the posterior parietal regions was observed in 11 or 23 (48%) patients with Alzheimer's disease and 2 of 31 (6%) patients with other forms of dementia [5].

High impact information on STX2

• Epimorphin: a mesenchymal protein essential for epithelial morphogenesis [6].
• The identification of protein factors, such as epimorphin, scatter factor, and activin, that induce epithelial branching and convergent extension-like movements in embryonic tissues are important breakthroughs in our understanding of the role of mesenchyme in epithelial morphogenesis [7].
• The vesicle-associated membrane proteins (VAMPs) 1 and 2 specifically bind the acceptor membrane proteins syntaxin 1A and 4 but not syntaxin 2 or 3 [8].
• Insulin-induced ATP release from human platelets correlated with the association of syntaxin 2 with the vesicle-associated membrane protein 3 but was not associated with the activation of alphaIIbbeta3 integrin [9].
• In lysates of A818-6 cells we detected the 34-and 31-kD isoforms and the dimers, and in lysates of fibroblasts the 150-kD tetramers of epimorphin additionally [10].

Chemical compound and disease context of STX2

• Novel and as yet rare non-O157 Shiga toxin (Stx)-producing Escherichia coli (STEC) serotypes are emerging in Europe. Two different sorbitol-fermenting STECs, O100:H- carrying the virulence gene stx2 and O127:H40 carrying stx1 and eae genes (found in two related subjects), were isolated from patients' stool samples [11].
• EPM was also more active than TMP against Moraxella catarrhalis, Neisseria meningitidis, and Bacteroides spp., but it was less active than TMP against all other gram-negative bacteria tested [12].
• Additionally, when mice were treated with ciprofloxacin, an antibiotic that induces the O157:H7 Stx2-converting phage, the animals were more susceptible to the Stx2d1-producing mutant [13].
• In addition, the toxicity of Stx2 alone, or in presence of LPS, is independent of the T cell compartment [14].

Biological context of STX2

• Epimorphin is known as a mesenchymal factor involved in epithelial morphogenesis [15].
• The predicted amino acid sequence of the rat epimorphin protein exhibited 96 and 86% identity with the mouse and human epimorphin proteins, respectively [16].
• Within the cosmid insert, nine epimorphin exons were identified and sequenced [16].
• The epimorphin gene is highly conserved among humans, mice, and rats and maps to human chromosome 7, mouse chromosome 5, and rat chromosome 12 [16].
• The presence of both the general transport proteins (NSF and SNAPs) and specific transport proteins (syntaxin 2 and 4) indicates that platelet exocytosis uses a molecular mechanism similar to other secretory cells such as neurons [17].

Anatomical context of STX2

• This suggests that, although syntaxin 3 is the main target SNARE operating in exocytic transport to the apical plasma membrane in certain epithelial cell types, syntaxin 2 may play an important role in this trafficking route in others [18].
• The recombinant epimorphin guided the endothelial cells to align themselves in tandem and to present a branched morphology in the three-dimensional culture system [15].
• Epithelial-mesenchymal interactions are crucial for various epithelial tissue organizations and epimorphin is one of the important signaling molecules from the mesenchyme [19].
• Immunohistochemistry and metalloproteinase activity assay demonstrated augmented expression of metalloproteinase induced by recombinant epimorphin in human alveolar epithelial cells [2].
• These results suggest that epimorphin is the primary morphogen in the mammary gland but that growth factors are necessary to achieve the appropriate cell numbers for the resulting morphogenesis to be visualized [20].

Associations of STX2 with chemical compounds

• Our major finding was that, in contrast to Stx, the active site of the A-subunit of Stx2 is accessible in the holotoxin, and a molecule of formic acid and a water molecule mimic the binding of the adenine base of the substrate [3].
• Closely following the change in ceramide level was an increase in the expression of globotriaosylceramide (Gb3), the receptor for Stx2 [21].
• Blackbody infrared radiative dissociation of the protonated B(5) ions of Stx2 at the +12 and +13 charge states proceeds, at reaction temperatures of 120 to 180 degrees C, predominantly by the ejection of a single subunit from the complex [22].
• Exposure to Stx1 and Stx2, 100 ng/ml, reduced cell viability to approximately 25% of control values after 24 h and 20 microM curcumin restored viability to nearly 75% of control [23].
• Cells were stimulated by Stx1 or Stx2 (5 ng/ml) with or without CV6209 addition (12-100 microg/ml) for various periods of time [24].

Physical interactions of STX2

• A fourth mutant protein, S48D, shows abolishment of syntaxin 3 interaction but binds syntaxin 2 at normal and syntaxin 1A at mildly reduced efficiency [18].

Regulatory relationships of STX2

• Apoptosis induced by Stx1 (200 ng/ml) and apoptosis induced by Stx2 (200 ng/ml) were maximal following incubation with cells for 24 h (94.3% +/- 1.8% and 81.7% +/- 5.2% of the cells, respectively) [25].
• The protective effect of curcumin against Stx1 and Stx2-induced injury to HK-2 was not related to its antioxidant properties [23].
• Apoptosis was not observed in A subunit-free preparations of the Stx1 B pentamer which competitively inhibited Stx2 B pentamer-mediated apoptosis [26].

Other interactions of STX2

• Double-labeled fluorescent images revealed expression of matrix metalloproteinase 2 in re-epithelialized cells overlying epimorphin-positive early fibrotic lesions [2].
• In comparison, the plasma membrane SNAREs syntaxin 2 and syntaxin 4 each inhibited basal exocytosis, but only syntaxin 4 significantly inhibited Ca(2+)-stimulated secretion [27].
• It is concluded that, under the solution conditions investigated, the homopentamer of Stx2 B subunit is thermodynamically less stable than that of Stx1 B subunit [22].
• In addition, this assay was shown to be specific, because neither Stx1 nor Stx2 bound to GM3, but both bound weakly to Gb4Cer [28].
• Multiplex polymerase chain reaction using primers specific for stx1 and stx2 detected STEC in 18% of cow stool samples, 50% of raw beef samples, and 1.4% and 0.6% of bloody and watery stool samples, respectively, from hospitalized diarrhea patients [29].

Analytical, diagnostic and therapeutic context of STX2

• The sequence analysis of a human homologue revealed that both of primary and predicted secondary structures of epimorphin are highly conserved among species and this molecule has some isoforms including a putative soluble type [19].
• Molecular cloning of human epimorphin: identification of isoforms and their unique properties [19].
• Northern and Western blotting analyses revealed that epimorphin expression in NSIP samples were significantly higher than those in control lungs and lungs with UIP [2].
• Stx1 and Stx2 were found to circulate in the plasma of mice following intravenous injection, and both toxins were cleared rapidly from the blood [30].
• Interaction of Shiga toxin from Escherichia coli with human intestinal epithelial cell lines and explants: Stx2 induces epithelial damage in organ culture [31].

References