Bacterial protein toxins and cell vesicle trafficking

A group of bacterial protein toxins interfere with vesicular trafficking inside cells. Clostridial neurotoxins affect mainly the highly regulated fusion of neurotransmitter- and hormone-containing vesicles with the plasma membrane. They cleave the three SNARE proteins: VAMP, SNAP-25 and syntaxin, and this selective proteolysis results in a blockade of exocytosis. TheHelicobacter pylori cytotoxin is implicated in the pathogenesis of gastroduodenal ulcers. It causes a progressive and extensive vacuolation of cells followed by necrosis, after a cytotoxin-induced alteration of membrane trafficking by late endosomes. Vacuoles originate from this compartment in a rab7-dependent process and swell because they are acidic and accumulate membrane-permeant amines.     

蛇神经毒素在毕赤酵母中的分泌表达及其分离纯化

文中主要研究了毕赤酵母基因工程菌的构建及其发酵表达产物蛇神经毒素的分离纯化条件。蛇神经毒素编码基因由本实验室设计、合成，并重组构建成表达质粒pPIC9k-hPK。经电穿孔将该质粒转化毕赤酵母GS115 (His-Mut+)，筛选His+Muts型菌株，经诱导表达，产物进行SDS- PAGE电泳鉴定，相对分子质量与理论值一致，目标蛋白经小试发酵产量可达350mg/L。利用超滤、离子交换树脂及分子筛分离纯化，产物经高效液相色谱(HPLC)分析纯度达92%。     

Cellular pathology induced by snake venom phospholipase A2 myotoxins and neurotoxins: common aspects of their mechanisms of action

A large variety of snake toxins evolved from PLA₂ digestive enzymes through a process of ‘accelerated evolution’. These toxins have different tissue targets, membrane receptors and mechanisms of alteration of the cell plasma membrane. Two of the most commonly induced effects by venom PLA₂s are neurotoxicity and myotoxicity. Here, we will discuss how these snake toxins achieve a similar cellular lesion, which is evolutionarily highly conserved, despite the differences listed above. They cause an initial plasma membrane perturbation which promotes a large increase of the cytosolic Ca²⁺ concentration leading to cell degeneration, following modes that we discuss in detail for muscle cells and for the neuromuscular junction. The different systemic pathophysiological consequences caused by these toxins are not due to different mechanisms of cell toxicity, but to the intrinsic anatomical and physiological properties of the targeted tissues and cells. Received 05 March 2008; received after revision 08 April 2008; accepted 29 April 2008     

The potent tremorgenic neurotoxins lolitrem B and aflatrem: A comparison of the tremor response in mice

Summary Tremor dose-response curves were determined for mice dosed with the ryegrass neurotoxin lolitrem B, and the tremorgenic mycotoxin aflatrem. A family of characteristic curves was revealed for each tremorgen, with lolitrem B eliciting a sustained tremor response persisting for over 24 h.     

动物肽类神经毒素基因工程研究进展

介绍了克隆动物肽类神经毒素cDNA和基因组基因克隆的方法,以及毒素cDNA结构和毒素蛋白前体的翻译后加工过程。概述了毒素蛋白基因组基因的结构及其mRNA前体的加工过程。综述了在毒素蛋白的基因工程方面已取得的进展,并对未来的发展前景进行了探讨。     

Quantitative cytophotometric analyses of mesenteric mast cell granulation in acute soman intoxicated rats

Summary Effects of the organophosphate neurotoxin soman on rat mesenteric mast cell granule content were determined using scanning-integrating microdensitometric analysis of individual cell metachromasia. Mast cell degranulation was evidenced both with sublethal (0.5 LD₅₀) and lethal (1.5 LD₅₀) dosages and as early as 3–10 min post-injection. These data indicate a possible contribution of mast cell autacoids in the genesis of organophosphate-induced respiratory and circulatory collapse.Supported by U.S. Army Medical Research and Development Command Contract DAMD-17-81-C-1202.