Forchlorfenuron (CPPU) causes disorganization of the cytoskeleton and dysfunction of human umbilical vein endothelial cells, and abnormal vascular development in zebrafish embryos

Gong，Guiyi1,2; Kam，Hiotong1; Tse，Yu chung2; Giesy，John P.3,4,5; Seto，Sai wang6; Lee，Simon Ming yuen1

2021-02-15

10.1016/j.envpol.2020.115791

ENVIRONMENTAL POLLUTION   影响因子和分区

0269-7491

1873-6424

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).

Blood vessels Crop growth promotor HUVECs Septin Toxicity

EI ; SCI

英语

其他

Science and Technology Development Fund, Macau SAR["0058/2019/A1","0016/2019/AKP"] ; University of Macau[MYRG2019-00105ICMS]

Environmental Sciences & Ecology

Environmental Sciences

WOS:000614114100002

ELSEVIER SCI LTD

20210109720259

Agricultural products ; Agricultural robots ; Aquatic organisms ; Metabolites ; Phosphorylation

Biology:461.9 ; Marine Science and Oceanography:471 ; Chemical Reactions:802.2 ; Agricultural Products:821.4

ENVIRONMENT/ECOLOGY

2-s2.0-85098565959

Scopus

1.State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences,University of Macau,Macao
2.Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research,Department of Biology,Southern University of Science and Technology (SUSTech),Shenzhen,518055,China
3.Toxicology Centre,University of Saskatchewan,Saskatoon,S7N 5B3,Canada
4.Department of Veterinary Biomedical Sciences,University of Saskatchewan,Saskatoon,S7N 5B4,Canada
5.Department of Environmental Sciences,Baylor University,Waco,76706,United States
6.Department of Applied Biology and Chemistry Technology,The Hong Kong Polytechnic University,Kowloon,Hung Hom,Hong Kong

Gong，Guiyi,Kam，Hiotong,Tse，Yu chung,et al. Forchlorfenuron (CPPU) causes disorganization of the cytoskeleton and dysfunction of human umbilical vein endothelial cells, and abnormal vascular development in zebrafish embryos[J]. ENVIRONMENTAL POLLUTION,2021,271.

Gong，Guiyi,Kam，Hiotong,Tse，Yu chung,Giesy，John P.,Seto，Sai wang,&Lee，Simon Ming yuen.(2021).Forchlorfenuron (CPPU) causes disorganization of the cytoskeleton and dysfunction of human umbilical vein endothelial cells, and abnormal vascular development in zebrafish embryos.ENVIRONMENTAL POLLUTION,271.

Gong，Guiyi,et al."Forchlorfenuron (CPPU) causes disorganization of the cytoskeleton and dysfunction of human umbilical vein endothelial cells, and abnormal vascular development in zebrafish embryos".ENVIRONMENTAL POLLUTION 271(2021).