Wang Pei-Jen, Chien Ming-Shan, Wu Fong-June, Chou Hong-Nong, Lee Shyh-Jye
Institute of Fisheries Science, National Taiwan University, Taipei, Taiwan, ROC.
Toxicon. 2005 Mar 1;45(3):303-8. doi: 10.1016/j.toxicon.2004.10.016. Epub 2004 Dec 10.
Microcystin-LR (MC-LR), a cyanobacterial toxin, is a potent inhibitor of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A). PP1 and PP2A are critical regulators in embryonic development. However, the effects of MC-LR in embryonic development have been controversial. MC-LR has been demonstrated to be highly toxic in medaka, but not in zebrafish or rabbit embryos. The causes of difference may be due to membrane impermeability that impaired the delivery of MC-LR into cytoplasm of zebrafish and rabbit embryos. Therefore, we microinjected MC-LR directly into developing zebrafish embryos and investigated the effects of MC-LR on embryonic development. We demonstrated that MC-LR induced the lethality of zebrafish embryos in a dose- and time-dependent manner. MC-LR also induced the loss of blastomere coherence via the interference of beta-catenin and cadherins distributions. Furthermore, the MC-LR treated fry revealed various developmental defects. These results suggested that MC-LR might affect the phosphorylation equilibrium of signaling molecules, including beta-catenin and cadherins, required early in zebrafish embryonic development.
微囊藻毒素-LR(MC-LR)是一种蓝藻毒素,是蛋白磷酸酶1(PP1)和蛋白磷酸酶2A(PP2A)的有效抑制剂。PP1和PP2A是胚胎发育中的关键调节因子。然而,MC-LR对胚胎发育的影响一直存在争议。MC-LR已被证明对青鳉具有高毒性,但对斑马鱼或兔胚胎则不然。差异的原因可能是膜不透性阻碍了MC-LR进入斑马鱼和兔胚胎的细胞质。因此,我们将MC-LR直接显微注射到发育中的斑马鱼胚胎中,并研究了MC-LR对胚胎发育的影响。我们证明,MC-LR以剂量和时间依赖性方式诱导斑马鱼胚胎的致死性。MC-LR还通过干扰β-连环蛋白和钙黏蛋白的分布诱导卵裂球黏附丧失。此外,经MC-LR处理的鱼苗表现出各种发育缺陷。这些结果表明,MC-LR可能会影响斑马鱼胚胎发育早期所需的信号分子(包括β-连环蛋白和钙黏蛋白)的磷酸化平衡。