Effect of ochratoxin A on redox-regulated transcription factors, antioxidant enzymes and glutathione-S-transferase in cultured kidney tubulus cells
Effect of ochratoxin A on redox-regulated transcription factors, antioxidant enzymes and glutathione-S-transferase in cultured kidney tubulus cells
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DOI：
10.1016/j.fct.2008.04.023
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发表时间：
2008-08-01
影响因子：
4.3
通讯作者：
Rimbach, G.
中科院分区：
文献类型：
--
作者：
Boesch-Saadatmandi, C.;Loboda, A.;Rimbach, G.
赭曲霉毒素A(OTA)是一种主要由赭曲霉和疣状青霉产生的真菌毒素，是一种世界性的食品和饲料污染物。太田油对肾脏有毒性，对啮齿类动物也是一种肾脏致癌物质。OTA显示其毒性的潜在分子和细胞机制尚未完全阐明。本文研究了赭曲霉毒素A对体外培养的肾小管上皮细胞氧化还原调节转录因子、抗氧化酶和谷胱甘肽-S-转移酶活性的影响。将融合的LLC-PK1细胞与不同浓度的OTA共同孵育24 h，流式细胞仪检测发现OTA可降低细胞内超氧化物歧化酶活性，增加细胞内活性氧水平。此外，OTA还导致GST mRNA和活性水平下调。较低的GST水平伴随着调节GST基因转录的激活蛋白-1(AP-1)和核因子-E2相关因子-2(Nrf2)的反式激活减少。目前的数据表明，可能由于AP-1和Nrf2依赖的信号转导途径导致的ROS生成增加和GST活性降低，可能是OTA所致肾毒性的中心环节。(C)2008爱思唯尔有限公司。保留所有权利。
Ochratoxin A (OTA), a mycotoxin mostly produced by Aspergillus ochraceus and Penicillium verrucosum, is a worldwide contaminant of food and feedstuff. OTA is nephrotoxic and a renal carcinogen in rodents. The underlying molecular and cellular mechanisms by which OTA exhibits its toxicity have yet not been fully clarified. In the present study the effects of ochratoxin A on the activity of redox-regulated transcription factors, antioxidant enzymes, as well as glutathione-S-transferase (GST) have been studied in cultured kidney tubulus cells (LLC-PK1). Confluent LLC-PK1 cells were incubated with increasing concentrations of OTA for 24 h. OTA decreased SOD activity and enhanced intracellular levels of reactive oxygen species (ROS) as measured by flow cytometry. Furthermore OTA resulted in a down-regulation of GST mRNA and activity levels. Lower GST levels were accompanied by a decreased transactivation of activator protein-1 (AP-1) and NF-E2-related factor-2 (Nrf2), which mediate GST gene transcription. Present data indicate that enhanced ROS production and an impairment of GST activity, possibly due to an AP-1 and Nrf2 dependent signal transduction pathway, may be centrally involved in OTA induced nephrotoxicity. (C) 2008 Elsevier Ltd. All rights reserved.