Sager P R, Matheson D W
Cellular and Reproductive Toxicology Department, ICI Americas Inc., Farmington, CT 06032.
Toxicology. 1988 May;49(2-3):479-92. doi: 10.1016/0300-483x(88)90034-0.
The neuronal response to several neurotoxic chemicals includes disruption of the cytoskeleton such as interactions with microtubules and altered distribution of neurofilaments. Methylmercury (microtubule disrupting) and acrylamide and 2,5-hexanedione (neurofilament disrupting) have been used in a cell culture (PtK2) system to distinguish the cytoskeletal targets of these compounds. Methylmercury caused disassembly of microtubules with secondary collapse of vimentin filaments (epithelial cell equivalent of neurofilaments) at higher concentrations; actin filaments were unaltered. This confirms that disruption of actin does not contribute to methylmercury-induced interference with mitosis. In contrast, both acrylamide and 2,5-hexanedione caused a perinuclear redistribution of vimentin filaments with sparing of microtubules. Biochemical studies revealed that 2,5-hexanedione treatment resulted in high molecular weight vimentin-immunoreactive species, presumably by cross-linking of proteins. Selective action of both acrylamide and 2,5-hexanedione on vimentin filaments and the similarity of effects suggest that a common mechanism of damage may occur whereby these compounds act directly on both vimentin and neurofilaments.
神经元对几种神经毒性化学物质的反应包括细胞骨架的破坏，如与微管的相互作用以及神经丝分布的改变。甲基汞（破坏微管）、丙烯酰胺和2,5 -己二酮（破坏神经丝）已被用于细胞培养（PtK2）系统，以区分这些化合物的细胞骨架靶点。甲基汞在较高浓度下会导致微管解聚，同时波形蛋白丝（上皮细胞中相当于神经丝）继发性塌陷；肌动蛋白丝未发生改变。这证实了肌动蛋白的破坏与甲基汞诱导的有丝分裂干扰无关。相比之下，丙烯酰胺和2,5 -己二酮都会导致波形蛋白丝在细胞核周围重新分布，而微管则不受影响。生化研究表明，2,5 -己二酮处理会产生高分子量的波形蛋白免疫反应性物质，可能是通过蛋白质交联形成的。丙烯酰胺和2,5 -己二酮对波形蛋白丝的选择性作用以及效应的相似性表明，可能存在一种共同的损伤机制，即这些化合物直接作用于波形蛋白和神经丝。
