Montecucco C, Gutiérrez J M, Lomonte B
Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José 2060, Costa Rica.
Cell Mol Life Sci. 2008 Sep;65(18):2897-912. doi: 10.1007/s00018-008-8113-3.
A large variety of snake toxins evolved from PLA(2) 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 PLA(2)s 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 Ca(2+) 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.
各种各样的蛇毒毒素通过“加速进化”过程从磷脂酶A2（PLA(2)）消化酶演变而来。这些毒素具有不同的组织靶点、膜受体以及改变细胞质膜的机制。蛇毒PLA(2)最常引发的两种效应是神经毒性和肌毒性。在此，我们将讨论这些蛇毒毒素如何造成一种在进化上高度保守的类似细胞损伤，尽管存在上述差异。它们会引发最初的质膜扰动，促使细胞质中钙离子浓度大幅升高，进而导致细胞退化，其作用方式我们将针对肌肉细胞和神经肌肉接头进行详细讨论。这些毒素所导致的不同全身病理生理后果并非源于不同的细胞毒性机制，而是由于靶组织和细胞固有的解剖学和生理学特性。
