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马兜铃酸——体外诱导大鼠肾近端小管细胞的转录组反应

Aristolochic acids - Induced transcriptomic responses in rat renal proximal tubule cells in vitro.

作者信息

Bloch Katarzyna M, Evans Andrew, Lock Edward A

机构信息

Liverpool John Moores University, Liverpool, UK.

出版信息

Genom Data. 2015 Jun 1;5:254-6. doi: 10.1016/j.gdata.2015.05.028. eCollection 2015 Sep.

DOI:10.1016/j.gdata.2015.05.028
PMID:26484264
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4584013/
Abstract

Aristolochic acids (AAs) are the active components of herbal drugs derived from Aristolochia species that have been used for medicinal purposes since antiquity. However, AAs have recently been discovered to be highly nephrotoxic and induced urothelial cancer in humans and malignant tumors in the kidney and urinary tract of rodents. In this study, we exposed rat renal proximal tubule cells in vitro to a sub-cytotoxic level of AAs at three different time points (6 h, 24 h and 72 h). We then analyzed the gene expression profile after the compound exposure. Functional analysis with Ingenuity Pathways Analysis and DAVID tools revealed that at the late time point (72 h) there are many significantly altered genes involved in cancer-related pathways such as p53 signaling. MIAMI-compliant microarray data are deposited in the NCBI GEO database under accession number GSE68687 and can be found at: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE68687.

摘要

马兜铃酸(AAs)是源自马兜铃属植物的草药中的活性成分,自古以来就被用于药用。然而,最近发现AAs具有高度肾毒性,并可导致人类尿路癌以及啮齿动物肾脏和尿路的恶性肿瘤。在本研究中,我们在体外将大鼠肾近端小管细胞暴露于亚细胞毒性水平的AAs中三个不同时间点(6小时、24小时和72小时)。然后我们分析了化合物暴露后的基因表达谱。使用Ingenuity Pathways Analysis和DAVID工具进行的功能分析显示,在较晚时间点(72小时),有许多参与癌症相关途径(如p53信号通路)的基因发生了显著改变。符合MIAMI标准的微阵列数据已存入NCBI GEO数据库,登录号为GSE68687,可在以下网址找到:http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE68687 。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5b4/4584013/520e025ab532/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5b4/4584013/520e025ab532/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5b4/4584013/520e025ab532/gr1.jpg

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本文引用的文献

1
Molecular evidence for an involvement of organic anion transporters (OATs) in aristolochic acid nephropathy.有机阴离子转运体(OATs)参与马兜铃酸肾病的分子证据。
Toxicology. 2009 Oct 1;264(1-2):74-9. doi: 10.1016/j.tox.2009.07.014. Epub 2009 Jul 28.
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p53 mutations as fingerprints for aristolochic acid: an environmental carcinogen in endemic (Balkan) nephropathy.p53突变作为马兜铃酸的指纹图谱:一种地方性(巴尔干)肾病中的环境致癌物。
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Aristolochic acid and the etiology of endemic (Balkan) nephropathy.
马兜铃酸与地方性(巴尔干地区)肾病的病因
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Mutagenesis. 2005 Jan;20(1):45-9. doi: 10.1093/mutage/gei007. Epub 2005 Jan 11.
5
Application of simplified in vitro screening tests to detect genotoxicity of aristolochic acid.应用简化的体外筛选试验检测马兜铃酸的遗传毒性。
Food Chem Toxicol. 2004 Dec;42(12):2021-8. doi: 10.1016/j.fct.2004.07.016.
6
Aristolochic acid as a probable human cancer hazard in herbal remedies: a review.马兜铃酸作为草药中潜在的人类致癌风险:综述
Mutagenesis. 2002 Jul;17(4):265-77. doi: 10.1093/mutage/17.4.265.
7
Misuse of herbal remedies: the case of an outbreak of terminal renal failure in Belgium (Chinese herbs nephropathy).草药的不当使用:比利时终末期肾衰竭暴发事件(中草药肾病)
J Altern Complement Med. 1998 Spring;4(1):9-13. doi: 10.1089/acm.1998.4.1-9.
8
Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays.用于细胞生长和存活的快速比色测定法:应用于增殖和细胞毒性测定。
J Immunol Methods. 1983 Dec 16;65(1-2):55-63. doi: 10.1016/0022-1759(83)90303-4.
9
Mutagenicity of the two main components of commercially available carcinogenic aristolochic acid in Salmonella typhimurium.市售致癌马兜铃酸的两种主要成分在鼠伤寒沙门氏菌中的致突变性。
Cancer Lett. 1984 May;23(1):97-101. doi: 10.1016/0304-3835(84)90067-3.
10
Tumour induction in mice following exposure to aristolochic acid.小鼠暴露于马兜铃酸后诱发肿瘤的情况。
Arch Toxicol. 1988;61(6):504-5. doi: 10.1007/BF00293699.