Disease relevance of St8sia2

• In comparison to the HX pups with euthyroid or STX mothers, the HX infants with CTX mothers also showed reduced weight gain (-57% and -40%, respectively) and tail growth (-40% and -34%, respectively) [1].
• The effect of chronic in utero hypoxia on voltage-sensitive Na+ channels in newborn rat brain was investigated by means of ligand binding and autoradiography with [3H]saxitoxin (STX, Na+ channel ligand) [2].
• Shiga toxin (Stx) plays a central role in the etiology of hemolytic uremic syndrome (HUS) associated with Stx-producing Escherichia coli infection [3].
• Severe polyuria was observed as an early event with no other obvious sequelae after Stx administration, in parallel with elevated urinary level of aquaporin 2 (AQP2) water channel protein that was determined by a sandwich EIA assay [3].
• High frequency and long duration of block can be attained if sufficiently high concentrations of STX are used, although latency is long and the doses used may produce systemic toxicity [4].

High impact information on St8sia2

• Saturable binding of STX was significantly higher in homogenized Schwann cells (410 +/- 37 fmol/mg of protein) than in intact Schwann cells (214 +/- 21 fmol/mg of protein) [5].
• Administration of STX or ALX to rats in vivo stimulated H2O2 generation and caused DNA fragmentation in pancreatic islets [6].
• We conclude from these studies that the presence of beta 1, but not beta 2, is required for the integrity of the STX/TTX binding site of the solubilized and purified rat brain sodium channel [7].
• Treatment of the channel with 1.0 M MgCl2 followed by sedimentation through sucrose gradients results in complete separation of beta 1 from the alpha-beta 2 complex and complete loss of [3H]saxitoxin (STX) binding activity [7].
• Although Stx is known to be the major virulence factor of the pathogen, it is still unclear whether Stx directly impairs renal cells in vivo to cause such histological changes and deterioration of renal function [8].

Chemical compound and disease context of St8sia2

• Surgical thyroidectomy (STX) of the mothers reduced the weight gain of HX and sham HX pups by 28% and 22%, respectively, but it did not affect tail growth in either group of pups, Their pups were either hypophysectomized (HX) or sham HX, and some pups were also chemically thyroidectomized (CTX) by tapazole injections [1].
• Frequency of satisfactory blocks and mean duration of block can be increased and systemic toxicity reduced if STX is administered with a vasoconstrictor agent [4].

Biological context of St8sia2

• Measurements were made of specific binding of [3H]saxitoxin (STX) and the frequency and rate of rise of spontaneously occurring action potentials, the physiological expression of Na-channel density [9].
• In a range of membrane potentials where the channels were open greater than 98% of the time, STX block was voltage-dependent, provided sufficient time was allowed to reach a steady state [10].
• From their voltage dependence and kinetics, it was possible to distinguish single-channel current fluctuations due to blocking and unblocking of the channels by STX from those caused by intrinsic channel gating [10].
• Northern blot analysis indicated a substantial down-regulation of ST8Sia II from high expression at postnatal day 2 to almost undetectable levels at the age of 6 months [11].
• We have isolated a cDNA clone for the rat homologue of PST and compared its amino acid and nucleotide sequence to that of rat STX [12].

Anatomical context of St8sia2

• In situ hybridization of selected brain regions at postnatal days 2, 11, and 21 confirmed the decline of ST8Sia II level in isocortex, hippocampus, and cerebellum [11].
• Scatchard analysis showed the channels in TH-treated myotubes to have lower affinity for STX than those in control cells [13].
• A22Na flux assay in irradiated synaptosomes directly demonstrated that [3H]STX binding sites and veratridine-stimulated, STX-blocked 22Na efflux had similar sensitivities to UV radiation [14].
• To assess the consequence of the direct action of Stx on renal cells, left kidneys of rats were perfused with Stx1 from the renal artery through the renal vein and then revascularized [8].
• To determine whether or not polyalpha2,8sialyltransferases are downregulated during the differentiation of oligodendrocytes, the enzyme activity and expression of ST8Sia II and ST8Sia IV mRNA at two stages of maturation in JS12/1 and JS3/16 oligodendrocytes were examined [15].

Associations of St8sia2 with chemical compounds

• Measurements were made of specific [3H]-saxitoxin (STX) binding, action potential properties, 86Rb-uptake and 2-deoxyglucose (2-DG) uptake [16].
• Treatment of cultures with cycloheximide or actinomycin D, inhibitors of protein and RNA synthesis, completely prevented the increase in STX-binding induced by GF treatment [9].
• 2. The binding of [3H]-lifarizine was unaffected by sodium channel toxins binding to site 1 (tetrodotoxin), site 3 (alpha-scorpion venom) or site 5 (brevetoxin), Furthermore, lifarizine at concentrations up to 10 microM had no effect on [3H]-saxitoxin (STX) binding to toxin site 1 [17].
• 2. The Na+ channel blockers saxitoxin (STX, 1 nM) and tetrodotoxin (TTX, 1 microM), whilst having little effect on resting spontaneous activity, virtually abolished the inhibitory actions of cicaprost (10 nM) and nicotine (3 microM); inhibitory responses to isoprenaline (20 nM) were not affected [18].
• We studied inbred rats that received pancreas transplants with either systemic (STX) or portal (PTX) venous drainage after prior induction of diabetes with streptozotocin and sham-operated controls [19].

Other interactions of St8sia2

• ST8Sia II was not detectable at any time point in the subependymal layer and the layers of the olfactory bulb [11].

Analytical, diagnostic and therapeutic context of St8sia2

• Surgical thyroidectomy (STX) of the mothers reduced the weight gain of HX and sham HX pups by 28% and 22%, respectively, but it did not affect tail growth in either group of pups, and it did not affect serum T4 levels in the sham HX infants [1].
• Fasting plasma glucose and insulin levels were similar in all 3 groups, but fasting plasma glucagon levels were elevated in STX (mean +/- SEM, 282+/-35 ng/L) in comparison to PTX rats (119+/-9 ng/L, P < .05), although the difference versus the control group (191+/-31 ng/L) was insignificant [19].
• Immunoblotting revealed that Stx treatment markedly induced an elevation in urinary AQP2 level and reduction in AQP2 protein in the renal plasma membranes [3].
• Using a competitive RT-PCR on RNA extracts from the HNS, we demonstrate furthermore a significant decrease in the expression levels of both STX and PST mRNAs in lactating versus virgin animals [20].
• STX (saxitoxin), alone and with various vasoconstrictor and local anesthetic agents, was evaluated for its ability to produce topical anesthesia on the rabbit cornea, peripheral nerve block in the rat, and epidural anesthesia in the dog [4].

References