Toxicological significance of renal Bcrp: Another potential transporter in the elimination of mercuric ions from proximal tubular cells.
Toxicological significance of renal Bcrp: Another potential transporter in the elimination of mercuric ions from proximal tubular cells.
复制标题
肾脏BCRP的毒理学意义：从近端管状细胞中消除汞离子的另一个潜在转运蛋白。
DOI：
10.1016/j.taap.2015.03.027
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发表时间：
2015-06-01
影响因子：
3.8
通讯作者：
Joshee, Lucy
中科院分区：
文献类型：
--
作者：
Bridges, Christy C.;Zalups, Rudolfs K.;Joshee, Lucy
关键词：
研究表明，无机汞（Hg 2+）从近端肾小管细胞分泌到管腔中与多药耐药相关蛋白2（Mrp 2）有关。考虑到Mrp 2和乳腺癌耐药蛋白（BCRP）之间的定位和底物特异性的相似性，我们假设BCRP也可能在近端肾小管分泌汞物质中发挥作用。为了验证这一假设，最初使用含有Bcrp的由内而外的膜囊泡检查Hg 2+的摄取。这些研究的结果表明，Bcrp可能能够运输某些共轭的Hg 2+。为了进一步研究Bcrp在处理汞离子和诱导Hg 2+诱导的肾病中的作用，将Sprague-Dawley和Bcrp敲除（bcrp−/−）大鼠静脉内暴露于无肾毒性（0.5 μmol · kg−1）、中度肾毒性（1.5 μmol · kg−1）或显著肾毒性（2.0 μmol · kg−1）剂量的HgCl 2。一般来说，Hg 2+在bcrp−/−大鼠器官中的蓄积量大于Sprague-Dawley大鼠，这表明Bcrp可能在Hg 2+从靶细胞输出中发挥作用。在肾脏内，bcrp−/−大鼠的细胞损伤和坏死比对照组更严重。坏死的模式，这是本地化的内部皮质和外部条纹的外部髓质是显着不同的观察到Mrp 2缺陷的动物。这些研究结果表明，BCRP可能参与选择汞物种的细胞出口，其在这种出口中的作用可能不同于Mrp 2。
Secretion of inorganic mercury (Hg2+) from proximal tubular cells into the tubular lumen has been shown to involve the multidrug resistance-associated protein 2 (Mrp2). Considering similarities in localization and substrate specificity between Mrp2 and the breast cancer resistance protein (Bcrp), we hypothesize that Bcrp may also play a role in the proximal tubular secretion of mercuric species. In order to test this hypothesis, the uptake of Hg2+ was examined initially using inside-out membrane vesicles containing Bcrp. The results of these studies suggest that Bcrp may be capable of transporting certain conjugates of Hg2+. To further characterize the role of Bcrp in the handling of mercuric ions and in the induction of Hg2+-induced nephropathy, Sprague-Dawley and Bcrp knockout (bcrp−/−) rats were exposed intravenously to a non-nephrotoxic (0.5 μmol • kg−1), a moderately nephrotoxic (1.5 μmol • kg−1) or a significantly nephrotoxic (2.0 μmol • kg−1) dose of HgCl2. In general, the accumulation of Hg2+ was greater in organs of bcrp−/− rats than in Sprague-Dawley rats, suggesting that Bcrp may play a role in the export of Hg2+ from target cells. Within the kidney, cellular injury and necrosis was more severe in bcrp−/− rats than in controls. The pattern of necrosis, which was localized in the inner cortex and the outer stripe of the outer medulla was significantly different from that observed in Mrp2-deficient animals. These findings suggest that Bcrp may be involved in the cellular export of select mercuric species and that its role in this export may differ from that of Mrp2.
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DOI：
10.1124/jpet.106.110379
发表时间：
2007-01-01
影响因子：
3.5
作者：
El-Sheikh, Azza A. K.;van den Heuvel, Jeroen J. M. W.;Russel, Frans G. M.
通讯作者：
Russel, Frans G. M.
影响因子：
3.5
作者：
Clarkson, Thomas W.;Vyas, Jayesh B.;Ballatorl, Nazzareno
通讯作者：
Ballatorl, Nazzareno
影响因子：
3.8
作者：
Bridges, Christy C.;Joshee, Lucy;Zalups, Rudolfs K.
通讯作者：
Zalups, Rudolfs K.
影响因子：
7.8
作者：
El-Sheikh, Azza A. K.;Greupink, Rick;Russel, Frans G. M.
通讯作者：
Russel, Frans G. M.
人类ABC转运蛋白ABCG2/BCRP在化学上的表达：分子癌疗法的基本和临床观点。
影响因子：
1.9
作者：
Noguchi K;Katayama K;Sugimoto Y
通讯作者：
Sugimoto Y