Characterization of zebrafish Abcc4 as an efflux transporter of organochlorine pesticides.
Characterization of zebrafish Abcc4 as an efflux transporter of organochlorine pesticides.
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斑马鱼 Abcc4 作为有机氯农药外排转运蛋白的表征
DOI：
10.1371/journal.pone.0111664
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Cui Z
中科院分区：
文献类型：
--
作者：
Lu X;Long Y;Lin L;Sun R;Zhong S;Cui Z
滴滴涕和林丹是剧毒有机氯农药，由于在发展中国家频繁使用，对环境和公众健康造成不利影响。ABCC 4/MRP 4是一种有机阴离子转运蛋白，介导多种外源性和内源性化合物（如环核苷酸和抗癌药物）的细胞外排;然而，ABCC 4及其直系同源物是否在有机氯农药的解毒中起作用仍不清楚。在这里，我们证明了斑马鱼Abcc 4在DDT和linetrazole的细胞外排中的作用。斑马鱼abcc 4基因在卵母细胞中表达，在发育胚胎的透镜、胰腺、鳃、肝脏、肠和膀胱以及成体组织中检测到其转录本。DDT和Lincoln能诱导abcc 4基因的表达，过表达abcc 4能显著降低DDT和Lincoln对LLC-PK 1细胞和胚胎的毒性和蓄积。相反，Abcc 4-G1188 D突变体的过表达废除了其转运功能，而不影响其底物结合活性，并使LLC-PK 1细胞和发育中的胚胎对有毒农药敏感。此外，谷胱甘肽（GSH）参与了细胞内农药的外排，DDT和DDT可诱导胚胎发育过程中ATP酶的活性。因此，斑马鱼Abcc 4在有机氯农药的细胞外排中起着重要作用，可作为一种潜在的分子标记用于水环境中DDT和杀虫剂污染的监测。
DDT and lindane are highly toxic organochlorine pesticides and posing adverse effects on the environment and public health due to their frequent usage in developing countries. ABCC4/MRP4 is an organic anion transporter that mediates cellular efflux of a wide range of exogenous and endogenous compounds such as cyclic nucleotides and anti-cancer drugs; however, it remains unclear whether ABCC4 and its orthologs function in the detoxification of organochlorine pesticides. Here, we demonstrated the roles of zebrafish Abcc4 in cellular efflux of DDT and lindane. Zebrafish abcc4 was maternally expressed in the oocytes and its transcripts were detected in the lens, pancreas, gills, liver, intestine and bladder of developing embryos and in adult tissues examined. DDT and lindane were able to induce the expression of abcc4 gene and overexpression of Abcc4 significantly decreased the cytotoxicity and accumulation of DDT and lindane in LLC-PK1 cells and developing embryos. In contrast, overexpression of an Abcc4-G1188D mutant abolished its transporter function without effects on its substrate binding activity, and sensitized LLC-PK1 cells and developing embryos to toxic pesticides. Moreover, glutathione (GSH) was involved in the efflux of cellular pesticides and ATPase activity in developing embryos can be induced by DDT or lindane. Thus, zebrafish Abcc4 plays crucial roles in cellular efflux of organochlorine pesticides and can be used a potential molecular marker for the monitor of DDT and lindane contamination in the aquatic environment.
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DOI：
10.1158/1078-0432.ccr-13-0980
发表时间：
2013-08-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Furmanski BD;Hu S;Fujita KI;Li L;Gibson AA;Janke LJ;Williams RT;Schuetz JD;Sparreboom A;Baker SD
通讯作者：
Baker SD
影响因子：
3.8
作者：
LAGADIC, L;CUANY, A;ECHAUBARD, M
通讯作者：
ECHAUBARD, M
影响因子：
4.5
作者：
Doyotte, A;Cossu, C;Vasseur, P
通讯作者：
Vasseur, P
影响因子：
2.6
作者：
Fitzpatrick, PJ;OHalloran, J;Walsh, AR
通讯作者：
Walsh, AR
影响因子：
4.1
作者：
Lai, LQ;Tan, TM
通讯作者：
Tan, TM