Microarray analysis of T-2 toxin-induced liver, placenta and fetal liver lesions in pregnant rats
Microarray analysis of T-2 toxin-induced liver, placenta and fetal liver lesions in pregnant rats
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DOI：
10.1016/j.etp.2005.02.005
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发表时间：
2005-08-01
影响因子：
--
通讯作者：
Doi, K
中科院分区：
文献类型：
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作者：
Sehata, S;Kiyosawa, N;Doi, K
妊娠第13天的孕鼠经口给予2 mg/kg T-2毒素，并在给药后1、3、6、9和12 h处死（HAT）。组织学上，肝、胎盘和胎肝中凋亡细胞的数量增加（分别在6、12和9-12 HAT时达到峰值）。为了检查基因表达谱，我们在两个选定的时间点进行微阵列分析，这些组织的基础上的TdT介导的dUTP缺口末端标记（TUNEL）染色的结果。氧化应激和凋亡相关基因的表达增加，检测到在母鼠的肝脏，胎盘和胎肝的T-2毒素处理的孕鼠在凋亡的高峰时间点。在这些组织中也检测到脂质代谢和药物代谢酶相关基因表达降低。提示丝裂原活化蛋白激酶（MAPK）通路可能参与T-2毒素诱导的细胞凋亡机制。此外，在这些组织中始终观察到c-jun基因表达增加。我们的研究结果表明，T-2毒素在孕鼠中引起的毒性机制是由于氧化应激，随后激活MAPK通路，最终诱导细胞凋亡。c-jun基因可能在T-2毒素诱导的细胞凋亡中起重要作用。(C)2005年Elsevier GmbH。All rights reserved.
Pregnant rats on day 13 of gestation were treated orally with 2 mg/kg of T-2 toxin and sacrificed at 1, 3, 6, 9 and 12 It after the treatment (HAT). Histopathologically, the number of apoptotic cells was increased in the liver, placenta and fetal liver (peaked at 6, 12 and 9-12 HAT, respectively). To examine the gene expression profiles, we performed microarray analysis of these tissues at two selected time points based on the results of the TdT-mediated dUTP nick end labeling (TUNEL) staining. Increased expression of oxidative stress- and apoptosis-related genes was detected in the liver of dams, placenta and fetal liver of pregnant rats treated with T-2 toxin at the peak time point of apoptosis. Decreased expression of lipid metabolism- and drug-metabolizing enzyme-related genes was also detected in these tissues. The results suggested that the mitogen-activated protein kinase (MAPK) pathway might be involved in the mechanism of T-2 toxin-induced apoptosis. In addition, increased expression of the c-jun gene was consistently observed in these tissues. Our results suggest that the mechanism of T-2 toxin-induced toxicity in pregnant rats is due to oxidative stress followed by the activation of the MAPK pathway, finally inducing apoptosis. The c-jun gene may play an important role in T-2 toxin-induced apoptosis. (C) 2005 Elsevier GmbH. All rights reserved.