Expression profiling of heat stress effects on mice fed ergot alkaloids
Expression profiling of heat stress effects on mice fed ergot alkaloids
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DOI：
10.1093/toxsci/kfl142
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发表时间：
2007-01-01
影响因子：
3.8
通讯作者：
Antoniou, Eric
中科院分区：
文献类型：
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作者：
Bhusari, Sachin;Liu, Zhilin;Antoniou, Eric
牛毛草中毒影响野生动物和家畜食用含有麦角生物碱的高羊茅饲料感染的内生真菌，Neotyphodium coenophialum。当动物在环境温度升高（夏季）期间食用受感染的牛毛草（E+）饲料时，观察到一系列统称为夏季衰退的表型疾病。其特征是体温过高，伴随着摄食量、生长、产奶量和生殖健康的下降。实验小鼠在热中性（TN）温度下也表现出牛毛草中毒的症状，表现为生长速度和生殖适应性降低。我们的目标是表征夏季型热应激（HS）和E+小鼠肝脏中基因表达的差异时，相比，在TN温度下喂食E+的小鼠。在HS（34 +/-1 ℃; n = 13; E+HS）或TN条件（24 +/-1 ℃; n = 14; E+TN）下，在47至60日龄之间的2周时间内给小鼠喂食E+饮食。使用DNA微阵列鉴定E+HS与E+TN之间差异表达的基因。41个基因在治疗组之间差异表达。使用定量实时PCR测量八个基因的表达。编码I期解毒酶的基因在E+HS小鼠肝脏中上调。已知这种解毒途径会产生活性氧化物质。我们观察到一个上调的基因参与保护对反应性氧化物种。参与从头脂肪生成和脂质转运的关键基因也上调。最后，参与DNA损伤控制和未折叠蛋白反应的基因下调。
Fescue toxicosis affects wild and domestic animals consuming ergot alkaloids contained in tall fescue forage infected with the endophytic fungus, Neotyphodium coenophialum. When animals are consuming infected fescue (E+) forage during periods of elevated ambient temperatures (summer), a range of phenotypic disorders collectively called summer slump is observed. It is characterized by hyperthermia, with an accompanying decrease in feed intake, growth, milk yield, and reproductive fitness. Laboratory mice also exhibit symptoms of fescue toxicosis at thermo-neutral (TN) temperature, as indicated by reduced growth rate and reproductive fitness. Our goal was to characterize the differences in gene expression in liver of mice exposed to summer-type heat stress (HS) and E+ when compared to mice fed E+ at TN temperature. Mice were fed E+ diet under HS (34 +/- 1 degrees C; n = 13; E+HS) or TN conditions (24 +/- 1 degrees C; n = 14; E+TN) for a period of 2 weeks between 47 and 60 days of age. Genes differentially expressed between E+HS versus E+TN were identified using DNA microarrays. Forty-one genes were differentially expressed between treatment groups. Expressions of eight genes were measured using quantitative real-time PCR. Genes coding for phase I detoxification enzymes were upregulated in E+HS mouse liver. This detoxification pathway is known to produce reactive oxidative species. We observed an upregulation of genes involved in the protection against reactive oxidative species. Key genes involved in de novo lipogenesis and lipid transport were also upregulated. Finally, genes involved in DNA damage control and unfolded protein responses were downregulated.