Hypersensitive assessment of aryl hydrocarbon receptor transcriptional activity using a novel truncated cyp1a promoter in zebrafish

doi:10.1096/fj.201701171R

CORC > 重庆绿色智能技术研究院 > 中国科学院重庆绿色智能技术研究院 > 环境与健康研究中心

	Hypersensitive assessment of aryl hydrocarbon receptor transcriptional activity using a novel truncated cyp1a promoter in zebrafish
	Luo, Juan-Juan 1,2; Su, Dong-Sheng 1,2; Xie, Shao-Lin 2,3; Liu, Yi 2; Liu, Pei 1; Yang, Xiao-Jun 1; Pei, De-Sheng2
刊名	FASEB JOURNAL
	2018-05-01
卷号	32 期号:5 页码:2814-2826
关键词	T-cyp1a TCDD biomarker tumorigenesis
ISSN号	0892-6638
DOI	10.1096/fj.201701171R
英文摘要	2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent organic pollutant (POP), an unintentional byproduct of various industrial processes, and a human carcinogen. The expression of the cytochrome P450 1A (cyp1a) gene is upregulated in the presence of TCDD through activating the aryl hydrocarbon receptor pathway in a dose-dependent manner. Several essential response elements, including the 8 potential xenobiotic response elements in the cyp1a promoter region, have been identified to be the main functional parts for the response to TCDD. Thus, we aimed to develop a convenient and sensitive biomonitoring tool to examine the level of POPs in the environment and evaluate its potential human health risks by TCDD. Here, we established a transgenic zebrafish model with a red fluorescent reporter gene (mCherry) using the truncated cyp1a promoter. Under exposure to TCDD, the expression pattern of mCherry in the reporter zebrafish mirrored that of endogenous cyp1a mRNA, and the primary target tissues for TCDD were the brain vessels, liver, gut, cloaca, and skin. Our results indicated that exposure of the embryos to TCDD at concentrations as low as 0.005 nM for 48 h, which did not elicit morphologic abnormalities in the embryos, markedly increased mCherry expression. In addition, the reporter embryos responded to other POPs, and primary liver cell culture of zebrafish revealed that Cyp1a protein was mainly expressed in the cytoplasm of liver cells. Furthermore, our transgenic fish embryos demonstrated that TCDD exposure can regulate the expression levels of several tumor-related factors, including epidermal growth factor, TNF-alpha, C-myc, proliferating cell nuclear antigen, TGF-beta, serine/threonine kinase (Akt), and phosphorylated Akt, suggesting that our transgenic fish can be used as a sensitive model to evaluate the carcinogenicity induced by TCDD exposure.
资助项目	Three Hundred Leading Talents in Scientific and Technological Innovation Program of Chongqing[CSTCCXLJRC201714] ; Key Application and Development Program of Chongqing Science and Technology Commission[cstc2014yykfC20004] ; Key Application and Development Program of Chongqing Science and Technology Commission[cstc2014yykfC20002] ; Natural Science Foundation of Guangdong Province[2015A030313440] ; Hundred Talents Program of Chinese Academy of Sciences ; Li Ka Shing Foundation
WOS研究方向	Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics ; Cell Biology
语种	英语
出版者	FEDERATION AMER SOC EXP BIOL
WOS记录号	WOS:000432528000040
内容类型	期刊论文
源URL	[http://119.78.100.138/handle/2HOD01W0/6478]
专题	环境与健康研究中心
通讯作者	Yang, Xiao-Jun; Pei, De-Sheng
作者单位	1.Shantou Univ, Med Coll, Ctr Neurosci, Shantou, Peoples R China 2.Chinese Acad Sci, Chongqing Inst Green & Intelligent Technol, Chongqing 400714, Peoples R China 3.South China Agr Univ, Coll Marine Sci, Guangzhou, Guangdong, Peoples R China
推荐引用方式 GB/T 7714	Luo, Juan-Juan,Su, Dong-Sheng,Xie, Shao-Lin,et al. Hypersensitive assessment of aryl hydrocarbon receptor transcriptional activity using a novel truncated cyp1a promoter in zebrafish[J]. FASEB JOURNAL,2018,32(5):2814-2826.
APA	Luo, Juan-Juan.,Su, Dong-Sheng.,Xie, Shao-Lin.,Liu, Yi.,Liu, Pei.,...&Pei, De-Sheng.(2018).Hypersensitive assessment of aryl hydrocarbon receptor transcriptional activity using a novel truncated cyp1a promoter in zebrafish.FASEB JOURNAL,32(5),2814-2826.
MLA	Luo, Juan-Juan,et al."Hypersensitive assessment of aryl hydrocarbon receptor transcriptional activity using a novel truncated cyp1a promoter in zebrafish".FASEB JOURNAL 32.5(2018):2814-2826.