Molecular analysis, developmental function and heavy metal-induced expression of ABCC5 in zebrafish
Molecular analysis, developmental function and heavy metal-induced expression of ABCC5 in zebrafish
复制标题
斑马鱼ABCC5的分子分析、发育功能及重金属诱导表达
DOI：
10.1016/j.cbpb.2010.09.005
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发表时间：
2011-01-01
影响因子：
2.2
通讯作者：
Cui, Zongbin
中科院分区：
文献类型：
--
作者：
Long, Yong;Li, Qing;Cui, Zongbin
ABCC5/MRP5是一种有机阴离子转运体，通过外排抗癌药物、毒物和第二信使cGMP参与组织防御和细胞信号转导，但其在斑马鱼中的生理功能尚不清楚。在此，我们报道了斑马鱼ABCC5的特性、时空表达、发育功能及其对重金属的转录反应。斑马鱼abcc5基因位于18号染色体上，由28个外显子组成。推导的斑马鱼ABCC5多肽由1426个氨基酸组成，与其他物种的序列具有很高的同源性。斑马鱼abcc5是母系表达的，其转录产物主要分布在发育中的胚胎的脑、晶状体、肝脏和肠道中。在成体中，斑马鱼abcc5广泛表达，在睾丸、脑、眼睛、卵巢、肠道和肾脏中表达水平较高，但在鳃、肝脏、心脏和肌肉中表达水平相对较低。内源性ABCC5活性的显性-负性阻断导致斑马鱼胚胎发育迟缓，p21信号通路活性明显增强，细胞内cGMP含量显着增加。此外，镉、铅、汞、砷均能显著诱导ZF4细胞和斑马鱼胚胎中abcc5的表达。重金属诱导的ABCC5主要在受精后96h的胚胎肝脏中表达。在成年斑马鱼中，这些重金属中的一种或多种显著诱导了脑、肠、肝、肾和卵巢中abcc5的表达。此外，ABCC5的过表达减轻了Cd对斑马鱼胚胎的毒性，但不影响汞或砷的毒性。因此，ABCC5可能通过输出第二信使分子和细胞外的毒物在斑马鱼的胚胎发育和重金属解毒中发挥积极的作用。(C)2010 Elsevier Inc.保留所有权利。
ABCC5/MRP5 is an organic anion transporter that participates in tissue defense and cellular signal transduction through efflux of anticancer drugs, toxicants and a second messenger cGMP, but its physiological functions in zebrafish remain to be defined. Herein, we report the characterization, spatiotemporal expression and developmental function of zebrafish ABCC5 and its transcriptional responses to heavy metals. Zebrafish abcc5 gene is located on chromosome 18 and comprised of 28 exons. The deduced polypeptide of zebrafish ABCC5 consists of 1426 amino acids, which shares high sequence identity with those from other species. Zebrafish abcc5 is maternally expressed and its transcripts are mainly distributed in brain, lens, liver and intestine of developing embryos. In adults, zebrafish abcc5 is extensively expressed, at higher levels in testis, brain, eye, ovary, intestine and kidney, but at relatively lower levels in gill, liver, heart and muscle. Blockage of endogenous ABCC5 activity by its dominant-negative led to the developmental retardation of zebrafish embryos in which activity of p21 signaling was markedly stimulated and cellular cGMP content was significantly increased. In addition, expression of abcc5 in ZF4 cells and zebrafish embryos was significantly induced by cadmium (Cd), lead (Pb), mercury (Hg) or arsenic (As). The induced expression of ABCC5 by heavy metals was mainly detected in the liver of embryos at 96-h post-fertilization (hpf). In adult zebrafish, expression of abcc5 in brain, intestine, liver, kidney and ovary was significantly induced by one or more of these heavy metals. Furthermore, overexpression of ABCC5 attenuated the toxicity of Cd to zebrafish embryos, but did not affect the toxicity of Hg or As. Thus, ABCC5 is likely to play an active role in embryonic development and heavy metal detoxification through the export of second messenger molecules and toxicants out of cells in zebrafish. (C) 2010 Elsevier Inc. All rights reserved.