Oukkache Naoual, Rosso Jean-Pierre, Alami Meriem, Ghalim Norredine, Saïle Rachid, Hassar Mohammed, Bougis Pierre E, Martin-Eauclaire Marie-France
Faculté de Médecine Secteur Nord, CNRS FRE 2738, BIMC, Institut Jean Roche, Université de la Méditerranée, bd Pierre Dramard, 13916 Marseille Cedex 20, France.
Toxicon. 2008 Apr;51(5):835-52. doi: 10.1016/j.toxicon.2007.12.012. Epub 2007 Dec 17.
Scorpion venoms are very complex mixtures of molecules, most of which are peptides displaying different kinds of biological activity. Indeed, these peptides specifically bind to a variety of pharmacological targets, in particular ionic channels located in prey tissues, resulting in neurotoxic effects. Toxins modulating Na+, K+, Ca2+ and Cl(-) currents have been described in scorpion venoms. In this work, we have used several specific antibodies raised against the most lethal scorpion toxins already described to screen the Moroccan scorpion Androctonus mauretanicus mauretanicus venom in order to characterize new compounds. This immunological screening was also implemented by toxicity tests in mice and with mass spectrometry study, providing new informations on the molecular composition of this venom. In fine, we were able to determine the molecular masses of 70-80 different compounds. According to the immunological data obtained, many toxins cross-react with three sera raised against the most lethal alpha-toxins found in North African scorpion venoms, but not at all with those raised against the main beta-toxins from South and North American venoms. Some of the previously described toxins from Androctonus mauretanicus mauretanicus venom could thus be detected by combining immunological tests, toxicity in mice and molecular masses. Among these toxins, one of them, which showed a mild cross-reaction with the serum raised against AaH I (a highly potent toxin from the venom of Androctonus australis), was identified as Amm III and fully sequenced.
蝎毒是非常复杂的分子混合物,其中大多数是具有不同生物活性的肽。实际上,这些肽能特异性结合多种药理学靶点,特别是猎物组织中的离子通道,从而产生神经毒性作用。蝎毒中已发现调节钠、钾、钙和氯离子电流的毒素。在这项研究中,我们使用了几种针对已描述的最致命蝎毒素产生的特异性抗体,对摩洛哥蝎种马氏金蝎毒液进行筛选,以鉴定新的化合物。这种免疫筛选还通过小鼠毒性试验和质谱研究来实施,从而获得了有关这种毒液分子组成的新信息。最终,我们能够确定70 - 80种不同化合物的分子量。根据获得的免疫数据,许多毒素与针对北非蝎毒中发现的最致命α毒素产生的三种血清发生交叉反应,但与针对南美和北美毒液中主要β毒素产生的血清完全不发生交叉反应。因此,通过结合免疫试验、小鼠毒性试验和分子量测定,可以检测出马氏金蝎毒液中一些先前已描述的毒素。在这些毒素中,有一种与针对AaH I(一种来自澳大利亚金蝎毒液的高效毒素)产生的血清有轻微交叉反应,被鉴定为Amm III并进行了全序列测定。