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家养火鸡和野生火鸡的肝转录组对黄曲霉毒素 B₁的比较反应。

Comparative Response of the Hepatic Transcriptomes of Domesticated and Wild Turkey to Aflatoxin B₁.

机构信息

Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN 55108, USA.

University of Minnesota Informatics Institute, University of Minnesota, Minneapolis, MN 55455, USA.

出版信息

Toxins (Basel). 2018 Jan 13;10(1):42. doi: 10.3390/toxins10010042.

Abstract

The food-borne mycotoxin aflatoxin B₁ (AFB₁) poses a significant risk to poultry, which are highly susceptible to its hepatotoxic effects. Domesticated turkeys () are especially sensitive, whereas wild turkeys () are more resistant. AFB₁ toxicity entails bioactivation by hepatic cytochrome P450s to the electrophilic exo-AFB₁-8,9-epoxide (AFBO). Domesticated turkeys lack functional hepatic GST-mediated detoxification of AFBO, and this is largely responsible for the differences in resistance between turkey types. This study was designed to characterize transcriptional changes induced in turkey livers by AFB₁, and to contrast the response of domesticated (susceptible) and wild (more resistant) birds. Gene expression responses to AFB₁ were examined using RNA-sequencing. Statistically significant differences in gene expression were observed among treatment groups and between turkey types. Expression analysis identified 4621 genes with significant differential expression (DE) in AFB₁-treated birds compared to controls. Characterization of DE transcripts revealed genes dis-regulated in response to toxic insult with significant association of Phase I and Phase II genes and others important in cellular regulation, modulation of apoptosis, and inflammatory responses. Constitutive expression of was significantly higher in wild birds and was significantly higher in AFB₁-treated birds when compared to controls for both genetic groups. This pattern was also observed by qRT-PCR in other wild and domesticated turkey strains. Results of this study emphasize the differential response of these genetically distinct birds, and identify genes and pathways that are differentially altered in aflatoxicosis.

摘要

食源性病原体黄曲霉毒素 B₁(AFB₁)对家禽构成重大风险,家禽对其肝毒性作用非常敏感。家养火鸡()特别敏感,而野生火鸡()则更具抵抗力。AFB₁毒性需要通过肝细胞色素 P450 进行生物激活,形成亲电的外-AFB₁-8,9-环氧化物(AFBO)。家养火鸡缺乏功能性的 GST 介导的 AFBO 解毒作用,这在很大程度上解释了火鸡类型之间抗性的差异。本研究旨在描述 AFB₁诱导的火鸡肝脏转录变化,并对比家养(敏感)和野生(更具抗性)鸟类的反应。使用 RNA 测序研究 AFB₁对基因表达的影响。在处理组和火鸡类型之间观察到基因表达的统计学显著差异。表达分析确定了 4621 个在 AFB₁处理的鸟类中与对照组相比具有显著差异表达(DE)的基因。对 DE 转录本的特征分析揭示了与毒性应激反应相关的基因的表达受到调控,这些基因与 I 相和 II 相基因以及其他在细胞调节、凋亡调节和炎症反应中重要的基因显著相关。在野生鸟类中,的组成型表达显著更高,与对照组相比,在 AFB₁处理的鸟类中也更高,对于两个遗传群体都是如此。这种模式在其他野生和家养火鸡品系的 qRT-PCR 中也得到了观察。本研究的结果强调了这些遗传上不同的鸟类的差异反应,并确定了在黄曲霉毒素中毒中差异改变的基因和途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c170/5793129/91bcf612715c/toxins-10-00042-g001.jpg

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