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Microcystin-LR exposure induced nephrotoxicity by triggering apoptosis in female zebrafish

机译:微囊藻毒素-LR暴露通过触发雌性斑马鱼的凋亡诱导肾毒性

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Recently, several studies showed that microcystin-LR (MCLR) can accumulate and induce toxicity in kidney. However, the exact mechanism is unknown. The aim of this study was to explore the mechanism of MCLR-induced nephrotoxicity. To this end, adult zebrafish were exposed to MCLR (0, 1, 5 and 25 mu g/L) for 60 days. Exposure to MCLR caused histopathological lesions, which were characterized by renal tubules filled with eosinophilic casts, abnormal renal tubules, intertubular space decrease, and blood infiltration in renal cells. RNA-Seq analysis indicated that exposure to MCLR significantly interfered with renal gene expressions, and these genes were enriched in various pathways, such as oxidative phosphorylation, cell cycle, and protein processing in endoplasmic reticulum, which were related to apoptosis. Furthermore, terminal deoxynucleotide transferase-mediated deoxy-UTP nick end labelling (TUNEL) assay showed that MCLR exposure induced renal cell apoptosis. In addition, negative changes of the reactive oxygen species (ROS) level as well as apoptotic-related gene, protein expressions and enzyme activities suggested that MCLR could induce production of ROS, subsequently triggering apoptosis via p53-bcl-2 and caspase-dependent pathway in the kidney of zebrafish. Therefore, it can be concluded that apoptosis is a primary case of MCLR-induced nephrotoxicity. (C) 2018 Elsevier Ltd. All rights reserved.
机译:最近,一些研究表明,微囊藻毒素-LR(MCLR)可以在肾脏中积累并诱导毒性。但是,确切的机制尚不清楚。这项研究的目的是探讨MCLR诱导的肾毒性的机制。为此,成年斑马鱼暴露于MCLR(0、1、5和25μg / L)60天。暴露于MCLR会引起组织病理学损害,其特征是充满肾小管的嗜酸性粒细胞,异常的肾小管,小管间空间减少以及肾细胞的血液浸润。 RNA-Seq分析表明,暴露于MCLR会显着干扰肾脏基因的表达,并且这些基因富含各种途径,例如氧化磷酸化,细胞周期和内质网中的蛋白质加工,这些途径与细胞凋亡有关。此外,末端脱氧核苷酸转移酶介导的脱氧-UTP缺口末端标记(TUNEL)分析表明,MCLR暴露可诱导肾细胞凋亡。此外,活性氧(ROS)水平以及凋亡相关基因,蛋白质表达和酶活性的负变化表明MCLR可以诱导ROS的产生,随后通过p53-bcl-2和caspase依赖性途径触发细胞凋亡。在斑马鱼的肾脏。因此,可以得出结论,凋亡是MCLR诱导的肾毒性的主要情况。 (C)2018 Elsevier Ltd.保留所有权利。

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