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p53 activation contributes to patulin-induced nephrotoxicity via modulation of reactive oxygen species generation

机译:p53激活通过调节活性氧的产生而促进巡视蛋白诱导的肾毒性

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摘要

Patulin is a major mycotoxin found in fungal contaminated fruits and their derivative products. Previous studies showed that patulin was able to induce increase of reactive oxygen species (ROS) generation and oxidative stress was suggested to play a pivotal role in patulin-induced multiple toxic signaling. The objective of the present study was to investigate the functional role of p53 in patulin-induced oxidative stress. Our study demonstrated that higher levels of ROS generation and DNA damage were induced in wild-type p53 cell lines than that found in either knockdown or knockout p53 cell lines in response to patulin exposure, suggesting p53 activation contributed to patulin-induced ROS generation. Mechanistically, we revealed that the pro-oxidant role of p53 in response to patulin was attributed to its ability to suppress catalase activity through up-regulation of PIG3. Moreover, these in vitro findings were further validated in the p53 wild-type/knockout mouse model. To the best of our knowledge, this is the first report addressing the functional role of p53 in patulin-induced oxidative stress. The findings of the present study provided novel insights into understanding mechanisms behind oxidative stress in response to patulin exposure.
机译:棒曲霉素是在真菌污染的水果及其衍生物中发现的主要真菌毒素。先前的研究表明,棒曲霉素能够诱导活性氧(ROS)生成增加,并且氧化应激被认为在棒曲霉素诱导的多种毒性信号中起关键作用。本研究的目的是研究p53在棒曲霉素诱导的氧化应激中的功能作用。我们的研究表明,野生型p53细胞系诱导的ROS产生和DNA损伤的水平要高于击倒或击倒p53细胞系,以响应于patulin暴露,这表明p53激活有助于patulin诱导ROS产生。从机理上讲,我们发现p53对棒曲霉素的促氧化作用归因于其通过上调PIG3抑制过氧化氢酶活性的能力。此外,这些体外研究结果在p53野生型/敲除小鼠模型中得到了进一步验证。据我们所知,这是第一个针对p53在巡视蛋白诱导的氧化应激中的功能性作用的报道。本研究的发现提供了新的见解,以了解氧化应激背后的机制对棒曲霉素暴露的理解。

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