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易感性和抗性火鸡脾脏中黄曲霉毒素 B 的基因反应改变。

Altered Gene Response to Aflatoxin B in the Spleens of Susceptible and Resistant Turkeys.

机构信息

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

Department of Animal, Dairy and Veterinary Sciences, College of Agriculture, Utah State University, Logan, UT 84322, USA.

出版信息

Toxins (Basel). 2019 Apr 28;11(5):242. doi: 10.3390/toxins11050242.

Abstract

Susceptibility and/or resistance to aflatoxin B (AFB) is a threshold trait governed principally by glutathione S transferase (GST)-mediated detoxification. In poultry, domesticated turkeys are highly sensitive to AFB, most likely due to dysfunction in hepatic GSTs. In contrast, wild turkeys are comparatively resistant to aflatoxicosis due to the presence of functional hepatic GSTAs and other possible physiological and immunological interactions. The underlying genetic basis for the disparate GST function in turkeys is unknown as are the broader molecular interactions that control the systemic response. This study quantifies the effects of dietary AFB on gene expression in the turkey spleen, specifically contrasting genetically distinct domesticated (DT, susceptible) and Eastern wild (EW, resistant) birds. Male turkey poults were subjected to a short-term AFB treatment protocol with feed supplemented with 320 ppb AFB beginning on day 15 of age and continuing for 14 days. Spleen tissues were harvested and subjected to deep RNA sequencing and transcriptome analysis. Analysis of differential gene expression found the effects of AFB treatment on the spleen transcriptomes considerably more prominent in the DT birds compared to EW. However, expression of the differentially expressed genes (DEGs) was directionally biased, with the majority showing higher expression in EW (i.e., down-regulation in DT). Significantly altered pathways included FXR/RXR and LXR/RXR activation, coagulation system, prothrombin activation, acute phase response, and atherosclerosis signaling. Differential extra-hepatic expression of acute phase protein genes was confirmed by quantitative real time PCR (qRT-PCR) in the original experiment and additional turkey lines. Results demonstrate that wild turkeys possess a capacity to more effectively respond to AFB exposure.

摘要

对黄曲霉毒素 B (AFB) 的易感性和/或抗性是由谷胱甘肽 S 转移酶 (GST) 介导的解毒作用主要控制的阈性状。在家禽中,驯化火鸡对 AFB 高度敏感,这很可能是由于肝 GSTs 功能障碍所致。相比之下,由于存在功能性肝 GSTAs 和其他可能的生理和免疫相互作用,野生火鸡对黄曲霉毒素中毒具有相对抗性。火鸡 GST 功能差异的潜在遗传基础以及控制全身反应的更广泛分子相互作用尚不清楚。本研究定量研究了日粮 AFB 对火鸡脾脏基因表达的影响,特别是对比了遗传上不同的驯化(DT,易感)和东部野生(EW,抗性)鸟类。雄性火鸡雏鸡从 15 日龄开始用添加 320 ppb AFB 的饲料进行短期 AFB 处理,持续 14 天。采集脾脏组织进行深度 RNA 测序和转录组分析。差异基因表达分析发现,AFB 处理对 DT 鸟类脾脏转录组的影响明显大于 EW 鸟类。然而,差异表达基因(DEGs)的表达方向偏向性,大多数基因在 EW 中表达更高(即 DT 中下调)。显著改变的途径包括 FXR/RXR 和 LXR/RXR 激活、凝血系统、凝血酶原激活、急性期反应和动脉粥样硬化信号转导。在原始实验和其他火鸡品系中,通过定量实时 PCR(qRT-PCR)证实了急性期蛋白基因的差异表达。结果表明,野生火鸡具有更有效地应对 AFB 暴露的能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3e3/6562755/3244da95ea94/toxins-11-00242-g001.jpg

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