Donghu Experimental Station of Lake Ecosystems, State Key Laboratory for Freshwater Ecology and Biotechnology of China, Institute of Hydrobiology, The Chinese Academy of Sciences, Wuhan, People's Republic of China.
PLoS One. 2011;6(7):e22676. doi: 10.1371/journal.pone.0022676. Epub 2011 Jul 29.
As cynobacterial blooms frequently occur in fresh waters throughout the world, microcystins (MCs) have caused serious damage to both wildlife and human health. MCs are known to have developmental toxicity, however, the possible molecular mechanism is largely unknown. This is the first toxicological study to integrate post-transcriptomic, proteomic and bioinformatics analysis to explore molecular mechanisms for developmental toxicity of MCs in zebrafish. After being microinjected directly into embryos, MC-RR dose-dependently decreased survival rates and increased malformation rates of embryos, causing various embryo abnormalities including loss of vascular integrity and hemorrhage. Expressions of 31 microRNAs (miRNAs) and 78 proteins were significantly affected at 72 hours post-fertilisation (hpf). Expressions of miR-430 and miR-125 families were also significantly changed. The altered expressions of miR-31 and miR-126 were likely responsible for the loss of vascular integrity. MC-RR significantly reduced the expressions of a number of proteins involved in energy metabolism, cell division, protein synthesis, cytoskeleton maintenance, response to stress and DNA replication. Bioinformatics analysis shows that several aberrantly expressed miRNAs and proteins (involved in various molecular pathways) were predicted to be potential MC-responsive miRNA-target pairs, and that their aberrant expressions should be the possible molecular mechanisms for the various developmental defects caused by MC-RR.
由于蓝藻水华经常在世界各地的淡水中发生,微囊藻毒素(MCs)对野生动物和人类健康造成了严重的损害。已知 MCs 具有发育毒性,但其可能的分子机制在很大程度上尚不清楚。这是首次将转录组学、蛋白质组学和生物信息学分析相结合,探索 MC 对斑马鱼发育毒性的分子机制的毒理学研究。在将 MC-RR 直接注射到胚胎中后,它会剂量依赖性地降低胚胎的存活率并增加畸形率,导致各种胚胎异常,包括血管完整性丧失和出血。在受精后 72 小时(hpf),31 种 microRNAs(miRNAs)和 78 种蛋白质的表达受到显著影响。miR-430 和 miR-125 家族的表达也发生了显著变化。miR-31 和 miR-126 的表达改变可能导致血管完整性丧失。MC-RR 显著降低了许多参与能量代谢、细胞分裂、蛋白质合成、细胞骨架维持、应激反应和 DNA 复制的蛋白质的表达。生物信息学分析表明,一些异常表达的 miRNA 和蛋白质(涉及多种分子途径)被预测为潜在的 MC 反应性 miRNA-靶对,它们的异常表达可能是 MC-RR 引起各种发育缺陷的可能分子机制。