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学科主题: Biochemistry & Molecular Biology
题名: Molecular analysis and heavy metal detoxification of ABCC1/MRP1 in zebrafish
作者: Long, Yong ; Li, Qing ; Cui, Zongbin
通讯作者: Cui, ZB, Chinese Acad Sci, Key Lab Biodivers & Conservat Aquat Organism, Inst Hydrobiol, 7 Donghu Rd, Wuhan 430072, Hubei, Peoples R China ; zbcui@ihb.ac.cn
关键词: ABC transporter ; ABCC1 ; Multidrug resistance ; Tissue defense ; Heavy metals
刊名: MOLECULAR BIOLOGY REPORTS
发表日期: 2011
卷: 38, 期:3, 页:1703-1711
收录类别: SCI
部门归属: [Long, Yong; Li, Qing; Cui, Zongbin] Chinese Acad Sci, Key Lab Biodivers & Conservat Aquat Organism, Inst Hydrobiol, Wuhan 430072, Hubei, Peoples R China; [Long, Yong] Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China
资助者: National Natural Science Foundation of China [30671602, 30871442]
摘要: ABCC1/MRP1 belongs to the ATP-binding cassette superfamily and its elevated expression is closely associated with the multidrug resistance of various tumor cells. In normal tissues, ABCC1 confers resistance to a wide variety of xenobiotics and toxicants, demonstrating its important roles in tissue defense. Here, we report the cloning and functional characterization of abcc1 gene in zebrafish. This gene is localized on zebrafish chromosome 3 and contains a 4,557 bp open-reading frame. The deduced polypeptide is composed of 1,518 amino acids, which shares 70% identity with human ABCC1. Phylogenetic analysis revealed that ABCC1 proteins from thirteen vertebrate species are highly conserved during evolution. Transcriptional expression of zebrafish abcc1 gene in developing embryos was examined by whole-mount in situ hybridization and real-time PCR. Transcripts of zebrafish abcc1 gene were detectable in four-cell stage embryos, indicating that this gene is maternally expressed. ABCC1 mRNAs were ubiquitously distributed in embryos before 12 h post-fertilization (hpf) and mainly localized in eyes and brain from 24 to 72 hpf, and in gills from 96 to 120 hpf. In addition, zebrafish abcc1 gene was highly expressed in 1-hpf embryos and detected in all adult tissues examined, with highest expression in testis and lowest in heart and liver. Exposure of ZF4 cells and embryos to CdCl2 center dot 2.5H(2)O, HgCl2, Pb(NO3)(2), or Na3AsO4 center dot 12H(2)O significantly induced transcriptional expression of abcc1 gene. Furthermore, overexpression of abcc1 improved the survival rates of embryos exposed to Cd, Hg or As, while overexpression of a abcc1 mutant (ABCC1-G1420D) sensitized zebrafish embryos to toxic metals. These data indicate that zebrafish ABCC1 has crucial roles in heavy metals detoxification.
语种: 英语
WOS记录号: WOS:000286941400033
ISSN号: 0301-4851
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内容类型: 期刊论文
URI标识: http://ir.ihb.ac.cn/handle/342005/15526
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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Long, Yong; Li, Qing; Cui, Zongbin.Molecular analysis and heavy metal detoxification of ABCC1/MRP1 in zebrafish,MOLECULAR BIOLOGY REPORTS,2011,38(3):1703-1711
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