Forchlorfenuron (CPPU) causes disorganization of the cytoskeleton and dysfunction of human umbilical vein endothelial cells, and abnormal vascular development in zebrafish embryos
Forchlorfenuron (CPPU) causes disorganization of the cytoskeleton and dysfunction of human umbilical vein endothelial cells, and abnormal vascular development in zebrafish embryos
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DOI：
10.1016/j.envpol.2020.115791
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发表时间：
2021-01-02
影响因子：
8.9
通讯作者：
Lee, Simon Ming-yuen
中科院分区：
文献类型：
--
作者：
Gong, Guiyi;Kam, Hiotong;Lee, Simon Ming-yuen
氯吡脲（CPPU）已在世界范围内使用，以增加各种农产品的尺寸和改善其质量。CPPU及其代谢产物具有持久性，经常在水果、水、沉积物和水生生物中检测到。虽然公众通过2011年中国镇江西瓜丑闻的爆发而了解了CPPU，但很少有人知道它对环境和野生动物的潜在影响。在这项研究中，CPPU对发育中的血管生成和血管系统，这是容易受到持久性毒物的侮辱，在体内斑马鱼胚胎（Danio rerio）的不良影响进行了研究。暴露于10 mg CPPU/L会损害存活和孵化，而暴露于2.5 mg CPPU/L则会阻碍发育。CPPU可明显抑制主静脉（CCV）、肠段间血管（ISV）和肠下血管（SIV）的发育，并呈剂量依赖性。此外，CPPU引起细胞骨架的紊乱。在体外培养的人脐静脉内皮细胞（HUVECs）中，CPPU抑制细胞增殖、迁移和管状结构的形成。Western blot分析结果显示，CPPU可增加HUVECs FLT-1的磷酸化，但抑制FAK及其下游MAPK通路的磷酸化。总之，CPPU对斑马鱼和HUVECs的发育内皮系统产生发育毒性。这至少部分是由于FAK/MAPK信号通路的抑制，而不是与VEGF受体（VEGFR）的直接相互作用。(C)2020爱思唯尔有限公司保留所有权利。
Forchlorfenuron (CPPU) has been used worldwide, to boost size and improve quality of various agricultural products. CPPU and its metabolites are persistent and have been detected frequently in fruits, water, sediments, and organisms in aquatic systems. Although the public became aware of CPPU through the exploding watermelon scandal of 2011 in Zhenjiang, China, little was known of its potential effects on the environment and wildlife. In this study, adverse effects of CPPU on developmental angiogenesis and vasculature, which is vulnerable to insults of persistent toxicants, were studied in vivo in zebrafish embryos (Danio rerio). Exposure to 10 mg CPPU/L impaired survival and hatching, while development was hindered by exposure to 2.5 mg CPPU/L. Developing vascular structure, including common cardinal veins (CCVs), intersegmental vessels (ISVs) and sub-intestinal vessels (SIVs), were significantly restrained by exposure to CPPU, in a dose-dependent manner. Also, CPPU caused disorganization of the cytoskeleton. In human umbilical vein endothelial cells (HUVECs), CPPU inhibited proliferation, migration and formation of tubular-like structures in vitro. Results of Western blot analyses revealed that exposure to CPPU increased phosphorylation of FLT-1, but inhibited phosphorylation of FAK and its downstream MAPK pathway in HUVECs. In summary, CPPU elicited developmental toxicity to the developing endothelial system of zebrafish and HUVECs. This was do, at least in part due to inhibition of the FAK/MAPK signaling pathway rather than direct interaction with the VEGF receptor (VEGFR). (C) 2020 Elsevier Ltd. All rights reserved.