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首页> 外文期刊>Journal of biochemical and molecular toxicology >Toxicities induced in cultured human hepatocarcinoma cells exposed to ochratoxin A: oxidative stress and apoptosis status.
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Toxicities induced in cultured human hepatocarcinoma cells exposed to ochratoxin A: oxidative stress and apoptosis status.

机译:暴露于曲霉毒素A的培养的人肝癌细胞中诱导的毒性:氧化应激和凋亡状态。

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摘要

Ochratoxin A (OTA) is a mycotoxin currently detected in stored animal and human food supplies as well as in human sera worldwide. OTA has diverse toxicological effects; however, the most prominent one is the nephrotoxicity. The present investigation was conducted to determine the molecular aspects of OTA toxicity in cultured human hepatocellular carcinoma cells. With this aim, we have monitored the effects of OTA on (i) cell viability, (ii) heat shock protein expressions as a parameter of protective and adaptive response, (iii) oxidative damage, and (iv) cell death signaling pathway. Our results clearly showed that OTA treatment inhibits cell proliferation, downregulates Hsp 70 and Hsp 27 protein and mRNA levels, and did not induce a significant reactive oxygen species generation. We have also demonstrated a decrease in mitochondrial membrane potential, a cytochrome c release, and an activation of caspase 9 and caspase 3 in response to OTA exposure. Moreover, OTA activates p53 expression, while some of its transcriptional target genes (Bax, Bak, PUMA, and p21) were found to downregulate. According to these data, we concluded that OTA may exert an inhibitory action on the transcriptional process. Besides, oxidative damage is not a major contributor to OTA toxicity. This mycotoxin induces a mitochondrial and caspase-dependent apoptotic cell death, which seems to be mediated by p53 transcriptional independent activities.
机译:ch曲霉毒素A(OTA)是一种霉菌毒素,目前已在动物和人类食物的储存以及全球人类血清中检测到。 OTA具有多种毒理作用。然而,最突出的是肾毒性。进行本研究以确定在培养的人肝癌细胞中OTA毒性的分子方面。为此,我们监测了OTA对(i)细胞活力,(ii)热激蛋白表达作为保护性和适应性反应参数,(iii)氧化损伤和(iv)细胞死亡信号通路的影响。我们的结果清楚地表明,OTA处理可抑制细胞增殖,下调Hsp 70和Hsp 27蛋白质和mRNA的水平,并且不会诱导显着的活性氧生成。我们还证明响应于OTA暴露,线粒体膜电位降低,细胞色素c释放以及caspase 9和caspase 3活化。此外,OTA激活p53的表达,同时发现其转录靶基因(Bax,Bak,PUMA和p21)下调。根据这些数据,我们得出结论,OTA可能在转录过程中发挥抑制作用。此外,氧化损伤不是OTA毒性的主要因素。这种霉菌毒素诱导线粒体和caspase依赖性凋亡细胞死亡,这似乎是由p53转录独立活性介导的。

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