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黄曲霉毒素 B1 和赭曲霉毒素 A 诱导的 LMH 细胞系转录组改变。

Transcriptomic alterations induced by aflatoxin B1 and ochratoxin A in LMH cell line.

机构信息

Department of Animal Life Science, Kangwon National University, Chuncheon-si, Gangwon-do 24341, Korea.

Department of Animal Science, University of California, Davis, Davis, CA 95616, USA.

出版信息

Poult Sci. 2020 Nov;99(11):5265-5274. doi: 10.1016/j.psj.2020.05.058. Epub 2020 Aug 7.

Abstract

Aflatoxin B1 (AFB1) and ochratoxin A (OTA), which are toxic metabolites of ubiquitously occurring molds, show diverse toxicological effects such as hepatotoxicity, genotoxicity, and immunotoxicity in human and animals. Despite poultry show sensitivity to AFB1 and OTA, the mechanism of these mycotoxins in chickens has not been fully investigated. Here, we aimed to elucidate the molecular mechanism induced by AFB1 and/or OTA in chicken hepatic cells using transcriptomic analysis. Aflatoxin B1 and OTA induced cytotoxic effects in a dose-dependent manner at 48 h after exposure. Furthermore, correlation effect indicated an antagonism between the 2 toxins. The mRNA sequencing of AFB1-treated or OTA-treated chicken hepatocarcinoma and functional analysis revealed the pathways that were commonly regulated by both mycotoxins, especially PPAR signaling, focal adhesion, and MAPK signaling. Based on these findings, a possible hypothesis is that AFB1 and OTA have similar toxic mechanisms and compete for some steps in the chicken liver, and it is expected that the mycotoxins would have antagonistic effects. In addition, genes identified through transcriptome analysis provide candidates for further study of AFB1 and OTA toxicity and targets for efforts to improve the health of chickens exposed to mycotoxins.

摘要

黄曲霉毒素 B1(AFB1)和赭曲霉毒素 A(OTA)是普遍存在的霉菌产生的有毒代谢物,在人类和动物中具有多种毒性作用,如肝毒性、遗传毒性和免疫毒性。尽管家禽对 AFB1 和 OTA 敏感,但这些霉菌毒素在鸡中的作用机制尚未完全研究清楚。在这里,我们旨在使用转录组分析阐明 AFB1 和/或 OTA 诱导的鸡肝细胞中的分子机制。AFB1 和 OTA 在暴露后 48 小时以剂量依赖的方式诱导细胞毒性作用。此外,相关性效应表明这两种毒素之间存在拮抗作用。AFB1 处理或 OTA 处理的鸡肝癌的 mRNA 测序和功能分析揭示了两种霉菌毒素共同调节的途径,特别是 PPAR 信号、黏附和 MAPK 信号。基于这些发现,可以假设 AFB1 和 OTA 具有相似的毒性机制,并在鸡肝中竞争某些步骤,预计霉菌毒素会产生拮抗作用。此外,通过转录组分析鉴定的基因为进一步研究 AFB1 和 OTA 的毒性以及为改善暴露于霉菌毒素的鸡的健康而努力提供了候选目标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e800/7647754/789e039d6064/gr1.jpg

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