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学科主题: Biochemistry & Molecular Biology; Endocrinology & Metabolism; Toxicology; Zoology
题名: Molecular characterization and functions of zebrafish ABCC2 in cellular efflux of heavy metals
作者: Long, Yong1; Li, Qing1; Zhong, Shan2; Wang, Youhui3; Cui, Zongbin1
通讯作者: Cui, ZB, Chinese Acad Sci, Inst Hydrobiol, Key Lab Biodivers & Conservat Aquat Organism, 7 Donghu Rd, Wuhan 430072, Hubei, Peoples R China ; zbcui@ihb.ac.cn
关键词: MRP ; ABCC2 ; Heavy metals ; Detoxification ; Zebra fish
刊名: COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
发表日期: 2011-05-01
DOI: 10.1016/j.cbpc.2011.01.002
卷: 153, 期:4, 页:381-391
收录类别: SCI
文章类型: Article
部门归属: [Long, Yong; Li, Qing; Cui, Zongbin] Chinese Acad Sci, Inst Hydrobiol, Key Lab Biodivers & Conservat Aquat Organism, Wuhan 430072, Hubei, Peoples R China; [Zhong, Shan] Wuhan Univ, Coll Basic Med, Wuhan 430072, Hubei, Peoples R China; [Wang, Youhui] Zhejiang Inst Freshwater Fisheries, Huzhou 313001, Zhejiang, Peoples R China
WOS标题词: Science & Technology ; Life Sciences & Biomedicine
资助者: National Natural Science Foundation of China [30671602, 30871442]
类目[WOS]: Biochemistry & Molecular Biology ; Endocrinology & Metabolism ; Toxicology ; Zoology
研究领域[WOS]: Biochemistry & Molecular Biology ; Endocrinology & Metabolism ; Toxicology ; Zoology
摘要: Multidrug-resistance associated protein 2 (MRP2/ABCC2) plays crucial roles in bile formation and detoxification by transporting a wide variety of endogenous compounds and xenobiotics, but its functions in zebrafish (Danio rerio) remain to be characterized. In this study, Ne obtained the full-length cDNA of zebrafish abcc2, analyzed its expression in developing embryos and adult tissues, investigated its transcriptional response to heavy metals, and evaluated its roles n efflux of heavy metals including cadmium, mercury and lead. Zebrafish abcc2 gene is located on chromosome 13 and composed of 32 exons. The deduced polypeptide of zebrafish ABCC2 consists of 1567 amino acids and possesses most of functional domains and critical residues defined in human ABCC2. Zebrafish abcc2 gene is not maternally expressed and its earliest expression was detected in embryos at 72 hpf. In larval zebrafish, abcc2 gene was found to be exclusively expressed in liver, intestine and pronephric tubules. In adult zebrafish, the highest expression of abcc2 gene was found in intestine followed by those in liver and kidney, while relative low expression was detected in brain and muscle. Expression of abcc2 in excretory organs including kidney, liver and intestine of zebrafish larvae was induced by exposure to 0.5 mu M mercury or 5 mu M lead. Moreover, exposure to 0.125-1 mu M of mercury or lead also significantly induced abcc2 expression in these excretory organs of adult zebrafish. Furthermore, overexpression of zebrafish ABCC2 in ZF4 cells and zebrafish embryos decreased the cellular accumulation of heavy metals including cadmium, mercury and lead as determined by MRE (metal responsive element)- or EPRE (electrophile response element)-driven luciferase reporters and atomic absorption spectrometry. These results suggest that zebrafish ABCC2/MRP2 is capable of effluxing heavy metals from cells and may play important roles in the detoxification of toxic metals. (C) 2011 Elsevier Inc. All rights reserved,
英文摘要: Multidrug-resistance associated protein 2 (MRP2/ABCC2) plays crucial roles in bile formation and detoxification by transporting a wide variety of endogenous compounds and xenobiotics, but its functions in zebrafish (Danio rerio) remain to be characterized. In this study, Ne obtained the full-length cDNA of zebrafish abcc2, analyzed its expression in developing embryos and adult tissues, investigated its transcriptional response to heavy metals, and evaluated its roles n efflux of heavy metals including cadmium, mercury and lead. Zebrafish abcc2 gene is located on chromosome 13 and composed of 32 exons. The deduced polypeptide of zebrafish ABCC2 consists of 1567 amino acids and possesses most of functional domains and critical residues defined in human ABCC2. Zebrafish abcc2 gene is not maternally expressed and its earliest expression was detected in embryos at 72 hpf. In larval zebrafish, abcc2 gene was found to be exclusively expressed in liver, intestine and pronephric tubules. In adult zebrafish, the highest expression of abcc2 gene was found in intestine followed by those in liver and kidney, while relative low expression was detected in brain and muscle. Expression of abcc2 in excretory organs including kidney, liver and intestine of zebrafish larvae was induced by exposure to 0.5 mu M mercury or 5 mu M lead. Moreover, exposure to 0.125-1 mu M of mercury or lead also significantly induced abcc2 expression in these excretory organs of adult zebrafish. Furthermore, overexpression of zebrafish ABCC2 in ZF4 cells and zebrafish embryos decreased the cellular accumulation of heavy metals including cadmium, mercury and lead as determined by MRE (metal responsive element)- or EPRE (electrophile response element)-driven luciferase reporters and atomic absorption spectrometry. These results suggest that zebrafish ABCC2/MRP2 is capable of effluxing heavy metals from cells and may play important roles in the detoxification of toxic metals. (C) 2011 Elsevier Inc. All rights reserved,
关键词[WOS]: CONJUGATE EXPORT PUMP ; MULTIDRUG-RESISTANCE PROTEIN-2 ; TROUT ONCORHYNCHUS-MYKISS ; KIDNEY PROXIMAL TUBULES ; MRP2 GENE ; INORGANIC MERCURY ; APICAL MEMBRANE ; OXIDATIVE STRESS ; RAT HEPATOCYTES ; CMRP/CMOAT GENE
语种: 英语
WOS记录号: WOS:000289383700003
ISSN号: 1532-0456
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.ihb.ac.cn/handle/342005/15668
Appears in Collections:水生生物分子与细胞生物学研究中心_期刊论文

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作者单位: 1.Chinese Acad Sci, Inst Hydrobiol, Key Lab Biodivers & Conservat Aquat Organism, Wuhan 430072, Hubei, Peoples R China
2.Wuhan Univ, Coll Basic Med, Wuhan 430072, Hubei, Peoples R China
3.Zhejiang Inst Freshwater Fisheries, Huzhou 313001, Zhejiang, Peoples R China

Recommended Citation:
Long, Yong; Li, Qing; Zhong, Shan; Wang, Youhui; Cui, Zongbin.Molecular characterization and functions of zebrafish ABCC2 in cellular efflux of heavy metals,COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY,2011,153(4):381-391
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