State Key Laboratory of Pollution Control and Resources Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China.
Toxicol Sci. 2011 Aug;122(2):395-405. doi: 10.1093/toxsci/kfr131. Epub 2011 May 20.
Microcystins (MCs) produced by cyanobacteria and their continuing "blooms" are a worldwide problem owing to the toxicity of microcystin-LR (MC-LR) to plants and animals. In the present study, we investigated membrane transport of MC-LR and its toxic effects on zebrafish embryos using fragmentation of embryos, scanning electron microscope (SEM), fluorescence microscopy, and toxic exposure tests. At a concentration < 0.04 mmol/l, MC-LR was predominantly adsorbed on outer membrane surface of embryos according to Langmuir isotherm. The absorption characteristics of MC-LR within the range from 0.05 to 0.4 mmol/l conformed to Freundlich isotherm model. At concentrations > 0.50 mmol/l MC-LR directly entered the cytoplasm via partition. Thinning and disruption of membranes was confirmed using SEM and fluorescence morphological observations. Exposure to different concentrations of MC-LR resulted in differences in membrane transport and toxicity characteristics. At low concentrations, more than 75% of the adsorbed MC-LR accumulated on the outer membrane surface and resulted in axial malformation, tail curving, and tail twisting. Increasing the concentration of MC-LR to between 0.05 and 0.4 mmol/l improved membrane transport and it was evident in cytoplasm of embryos, resulting in serious pericardial edema, hatching gland edema, hemagglutination, hemorrhage, and vacuolization. At > 0.50 mmol/l, more than 70% of the adsorbed MC-LR entered the cytoplasm and this was lethal to the embryos. The current research outlines a new method and mechanism for the transmembrane transport of large molecular weight organic compounds and could be important for studies concerning molecular toxicology.
微囊藻毒素(MCs)由蓝藻产生,且其持续“水华”是一个全球性的问题,这是由于微囊藻毒素-LR(MC-LR)对植物和动物的毒性。在本研究中,我们通过胚胎破碎、扫描电子显微镜(SEM)、荧光显微镜和毒性暴露试验,研究了 MC-LR 的膜转运及其对斑马鱼胚胎的毒性作用。在浓度<0.04mmol/L 时,根据朗缪尔等温线,MC-LR 主要吸附在胚胎的外膜表面。在 0.05-0.4mmol/L 的范围内,MC-LR 的吸收特性符合弗雷德里希等温线模型。在浓度>0.50mmol/L 时,MC-LR 通过分配直接进入细胞质。SEM 和荧光形态学观察证实了膜的变薄和破坏。暴露于不同浓度的 MC-LR 导致膜转运和毒性特征的差异。在低浓度时,超过 75%的吸附 MC-LR 积累在外膜表面,导致轴向畸形、尾巴弯曲和扭曲。增加 MC-LR 的浓度至 0.05-0.4mmol/L 之间,改善了膜转运,这在胚胎的细胞质中表现明显,导致严重的心包水肿、孵化腺水肿、红细胞凝集、出血和空泡化。在浓度>0.50mmol/L 时,超过 70%的吸附 MC-LR 进入细胞质,这对胚胎是致命的。本研究概述了一种新的方法和机制,用于大分子量有机化合物的跨膜转运,这对于分子毒理学研究可能很重要。