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细胞骨架作为有机磷化合物的非胆碱能靶点。

The cytoskeleton as a non-cholinergic target of organophosphate compounds.

机构信息

Department of Toxicology, Center for Research and Advanced Studies of the National Polytechnic Institute. Av. IPN 2508, San Pedro Zacatenco, C.P. 07360, Mexico City, Mexico.

Department of Toxicology, Center for Research and Advanced Studies of the National Polytechnic Institute. Av. IPN 2508, San Pedro Zacatenco, C.P. 07360, Mexico City, Mexico.

出版信息

Chem Biol Interact. 2021 Sep 1;346:109578. doi: 10.1016/j.cbi.2021.109578. Epub 2021 Jul 13.

Abstract

Current organophosphate (OP) toxicity research now considers potential non-cholinergic mechanisms for these compounds, since the inhibition of acetylcholinesterase (AChE) cannot completely explain all the adverse biological effects of OP. Thanks to the development of new strategies for OP detection, some potential molecular targets have been identified. Among these molecules are several cytoskeletal proteins, including actin, tubulin, intermediate filament proteins, and associated proteins, such as motor proteins, microtubule-associated proteins (MAPs), and cofilin. in vitro, ex vivo, and some in vivo reports have identified alterations in the cytoskeleton following OP exposure, including cell morphology defects, cells detachments, intracellular transport disruption, aberrant mitotic spindle formation, modification of cell motility, and reduced phagocytic capability, which implicate the cytoskeleton in OP toxicity. Here, we reviewed the evidence indicating the cytoskeletal targets of OP compounds, including their strategies, the potential effects of their alterations, and their possible participation in neurotoxicity, embryonic development, cell division, and immunotoxicity related to OP compounds exposure.

摘要

目前,有机磷(OP)毒性研究现在考虑了这些化合物的潜在非胆碱能机制,因为乙酰胆碱酯酶(AChE)的抑制不能完全解释 OP 的所有不良生物学效应。由于 OP 检测的新策略的发展,已经确定了一些潜在的分子靶标。这些分子包括几种细胞骨架蛋白,如肌动蛋白、微管蛋白、中间丝蛋白和相关蛋白,如马达蛋白、微管相关蛋白(MAPs)和丝切蛋白。在体外、离体和一些体内报告中,已经确定了 OP 暴露后细胞骨架的改变,包括细胞形态缺陷、细胞脱落、细胞内运输中断、有丝分裂纺锤体形成异常、细胞迁移能力改变和吞噬能力降低,这表明细胞骨架与 OP 毒性有关。在这里,我们综述了表明 OP 化合物的细胞骨架靶标的证据,包括它们的策略、它们改变的潜在影响,以及它们在与 OP 化合物暴露相关的神经毒性、胚胎发育、细胞分裂和免疫毒性中的可能参与。

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