Other Toxins (other + toxin)

Distribution by Scientific Domains

Selected Abstracts

Identification and Regulation of Genes from a Biocontrol Strain of Fusarium oxysporum

D. R. Fravel
Abstract Differential display with three time points revealed that thiram altered expression of numerous genes in the biocontrol fungus Fusarium oxysporum CS-20. Of the 101 bands purified from the differential display gel, 86 were successfully cloned, and 64 sequenced. Based on nucleic acid sequences, homology to known products was found using BLASTn for 26 sequences and homology to hypothetical proteins was found for six sequences, also from Gibberella zeae. One band (BM1 24-1) showed homology to an ABC transporter from three different fungi. Because of its association with detoxification functions, the ABC transporter was selected for further study. Mycelia of CS-20 were exposed to 25 ,g active ingredient (a.i.) thiram in liquid culture for various times from 0 to 8 h. Quantitative real-time PCR was used to evaluate gene expression. At 30 min after treatment with thiram, the ABC transporter was upregulated 20- to 25-fold relative to the control treatment. The ABC transporter was upregulated 15-fold at 1 h after treatment and 10-fold at 2 h. At 8 h after treatment, there was no difference between treated and non-treated for expression of the ABC transporter. Transcription of the gene encoding EST BM1 24-1 is induced in response to thiram treatment and may function in providing resistance in F. oxysporum isolate CS-20 to fungicides and other toxins. Tolerance to toxins may be critical to the successful inclusion of CS-20 in disease control strategies in cropping systems. [source]

Role of circulating neurotoxins in the pathogenesis of hepatic encephalopathy: potential for improvement following their removal by liver assist devices

Roger F. Butterworth
Abstract Both acute and chronic liver failure result in impaired cerebral function known as hepatic encephalopathy (HE). Evidence suggests that HE is the consequence of the accumulation in brain of neurotoxic and/or neuroactive substance including ammonia, manganese, aromatic amino acids, mercaptans, phenols, short-chain fatty acids, bilirubin and a variety of neuroactive medications prescribed as sedatives to patients with liver failure. Brain ammonia concentrations may attain levels in excess of 2 mm, concentrations which are known to adversely affect both excitatory and inhibitory neurotransmission as well as brain energy metabolism. Manganese exerts toxic effects on dopaminergic neurones. Prevention and treatment of HE continues to rely heavily on the reduction of circulating ammonia either by reduction of gut production using lactulose or antibiotics or by increasing its metabolism using l -ornithine- l -aspartate. No specific therapies have so far been designed to reduce circulating concentrations of other toxins. Liver assist devices offer a potential new approach to the reduction of circulating neurotoxins generated in liver failure. In this regard, the Molecular Absorbents Recirculating System (MARS) appears to offer distinct advantages over hepatocyte-based systems. [source]

Crystallization and preliminary X-ray diffraction data analysis of stenodactylin, a highly toxic type 2 ribosome-inactivating protein from Adenia stenodactyla

Giovanna Tosi
Ribosome-inactivating proteins (RIPs) inhibit protein synthesis and induce cell death by removing a single adenine from a specific rRNA loop. They can be divided into two main groups: type 1 and type 2 RIPs. Type 1 RIPs are single-chain enzymes with N-glycosidase activity. Type 2 RIPs contain two chains (A and B) linked by a disulfide bond. The A chain has RIP enzymatic activity, whereas the B chain shows lectin activity and is able to bind to glycosylated receptors on the cell surface. Stenodactylin is a type 2 RIP from the caudex of Adenia stenodactyla from the Passifloraceae family that has been recently purified and characterized. It shows a strong enzymatic activity towards several substrates and is more cytotoxic than other toxins of the same type. Here, the crystallization and preliminary X-ray diffraction data analysis of stenodactylin are reported. This RIP forms crystals that diffract to high resolution (up to 2.15,). The best data set was obtained by merging data collected from two crystals. Stenodactylin crystals belonged to the centred monoclinic space group C2 and contained two molecules in the asymmetric unit. [source]

Snake venom hyaluronidase: a therapeutic target

K. Kemparaju
Abstract The diffusion of toxins from the site of a bite into the circulation is essential for successful envenomation. Degradation of hyaluronic acid in the extracellular matrix (ECM) by venom hyaluronidase is a key factor in this diffusion. Hyaluronidase not only increases the potency of other toxins but also damages the local tissue. In spite of its important role, little attention has been paid to this enzyme. Hyaluronidase exists in various isoforms and generates a wide range of hyaluronic acid degradation products. This suggests that beyond its role as a spreading factor venom hyaluronidase deserves to be explored as a possible therapeutic target for inhibiting the systemic distribution of venom and also for minimizing local tissue destruction at the site of the bite. Copyright 2005 John Wiley & Sons, Ltd. [source]

Modification of epithelial cell barrier permeability and intercellular junctions by Clostridium sordellii lethal toxins

Catherine Boehm
Summary Clostridium sordellii lethal toxin (LT) is a glucosyltransferase which inactivates small GTPases from the Rho and Ras families. In the present work, we studied the effects of two variants, LT82 and LT9048, on the integrity of epithelial cell barrier using polarized MCCD (Mouse Cortical Collecting Duct) and MDCK (Madin-Darby Canine Kidney) cells. Our results demonstrate for the first time that LTs have very limited effects on tight junctions. In contrast, we show that both toxins modified the paracellular permeability within 2,4 h. Concomitantly LT82 and LT9048 induced a disorganization of basolateral actin filaments, without modifying apical actin. Both toxins mainly altered adherens junctions by removing E-cadherin-catenin complexes from the membrane to the cytosol. Similar effects on adherens junctions have been observed with other toxins, which directly or indirectly depolymerize actin. Thereby, Rac, a common substrate of both LTs, might play a central role in LT-dependent adherens junction alteration. Here, we show that adherens junction perturbation induced by LTs results neither from a direct effect of toxins on adherens junction proteins nor from an actin-independent Rac pathway, but rather from a Rac-dependent disorganization of basolateral actin cytoskeleton. This further supports that a dynamic equilibrium of cortical actin filaments is essential for functional E-cadherin organization in epithelia. [source]

Concentrations of dioxins and other organochlorines (PCBs, DDTs, HCHs) in human milk from Seveso, Milan and a Lombardian rural area in Italy: a study performed 25 years after the heavy dioxin exposure in Seveso

J Weiss
Aim: To investigate whether those who were exposed to high levels of the dioxin TCDD 25 years ago in Seveso, northern Italy still have higher than the expected levels of dioxins in their fat stores, and to investigate the concentrations of dioxins in the breast milk of mothers in Seveso and in two other regions in Italy. The load of vertically transmitted dioxins to the next generation, if being breastfed, was also investigated. Methods: As there may be a synergistic effect of mixtures of organic chlorines, the concentrations of pesticides such as DDTs and PCBs have also been studied in the same human milk samples. Breast milk from 12 mothers from Seveso, Central Milan and a Lombardian village was collected for analysis during the first week and 1 and 3 mo after delivery. Individual samples were used for the analysis of pesticides and PCBs, whereas dioxins were analysed in pooled samples from all 12 mothers on each occasion. Results: In human milk from Seveso, the TCDD concentration in fat calculated on a fresh weight basis was more than twice as high as the level in the other two regions, whereas the concentrations of investigated other toxins were lower in Seveso possible due to induction of the enzyme cytochrome P4501A, which means that the total level of dioxins was the same in all three locations. The congener profile, measured as mean toxic equivalency (TEQ) values, was the same in the Italian samples as previously reported from Stockholm. The calculations are based on the most recent WHO TCDD equivalency factors (TEF). The DDE concentration was higher in the samples from Milan than in the samples from the other two Italian regions, which may be due to the fact that, to a greater extent than in the other regions, Milanese food is imported from countries where DDT is still used as a pesticide. Conclusion: Twenty-five years after the dioxin catastrophe, human milk from mothers in Seveso has concentrations of the highly toxic dioxin congener TCDD that are more than twice as high as those in central Milan and a Lombardian village. This means that breastfed infants in Seveso still store an appreciable amount of TCDD in their body fat. The health consequences of this fact remain to be elucidated. The effect of the high load of DDTs in central Milan also has to be considered [source]