Age and sex dependent changes in liver gene expression during the life cycle of the rat.
Age and sex dependent changes in liver gene expression during the life cycle of the rat.
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DOI：
10.1186/1471-2164-11-675
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发表时间：
2010-11-30
期刊：
影响因子：
4.4
通讯作者：
Fuscoe JC
中科院分区：
文献类型：
--
作者：
Kwekel JC;Desai VG;Moland CL;Branham WS;Fuscoe JC
与年龄和性别相关的药物不良反应和疾病易感性是了解药物安全性和疾病进展的关键问题。我们假设，在不同生命周期阶段表达的潜在肝脏基因组将影响药物不良反应的易感性。了解基础肝脏基因表达模式是解决这一假设的必要的第一步，并将为我们评估药物不良反应提供信息，因为肝脏在药物代谢和生物转化中起着核心作用。在2、5、6、8、15、21、52、78和104周龄处死未给药雄性和雌性F344大鼠。收集肝组织进行组织学和基因表达分析。使用全基因组大鼠微阵列查询全局表达谱。使用基于p值（p < 0.05）和倍数变化（+/-1.5）的标准选择差异表达基因的初始列表。三维主成分分析显示，从第2周开始，雄性和雌性之间存在差异，从第5周开始，差异更大。最大的性别差异出现在8 - 52周之间，然后在104周再次收敛。K-means聚类确定了显示与年龄相关的表达模式的基因组。各种成年衰老相关的集群代表与异生质代谢，DNA损伤修复和氧化应激相关的基因途径。这些结果表明，潜在的作用，基因在特定的集群在增强年龄和性别相关的差异，对健康的不利影响的易感性。此外，基因表达的生命周期变化的这种全面的图片加深了我们的理解，并告知肝脏基因表达生物标志物的效用。
Age- and sex-related susceptibility to adverse drug reactions and disease is a key concern in understanding drug safety and disease progression. We hypothesize that the underlying suite of hepatic genes expressed at various life cycle stages will impact susceptibility to adverse drug reactions. Understanding the basal liver gene expression patterns is a necessary first step in addressing this hypothesis and will inform our assessments of adverse drug reactions as the liver plays a central role in drug metabolism and biotransformation. Untreated male and female F344 rats were sacrificed at 2, 5, 6, 8, 15, 21, 52, 78, and 104 weeks of age. Liver tissues were collected for histology and gene expression analysis. Whole-genome rat microarrays were used to query global expression profiles. An initial list of differentially expressed genes was selected using criteria based upon p-value (p < 0.05) and fold-change (+/- 1.5). Three dimensional principal component analyses revealed differences between males and females beginning at 2 weeks with more divergent profiles beginning at 5 weeks. The greatest sex-differences were observed between 8 and 52 weeks before converging again at 104 weeks. K-means clustering identified groups of genes that displayed age-related patterns of expression. Various adult aging-related clusters represented gene pathways related to xenobiotic metabolism, DNA damage repair, and oxidative stress. These results suggest an underlying role for genes in specific clusters in potentiating age- and sex-related differences in susceptibility to adverse health effects. Furthermore, such a comprehensive picture of life cycle changes in gene expression deepens our understanding and informs the utility of liver gene expression biomarkers.
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来自毒理基因组学研究基因基因表达水平的变化来源研究动物跨多个实验室。
影响因子：
4.4
作者：
Boedigheimer MJ;Wolfinger RD;Bass MB;Bushel PR;Chou JW;Cooper M;Corton JC;Fostel J;Hester S;Lee JS;Liu F;Liu J;Qian HR;Quackenbush J;Pettit S;Thompson KL
通讯作者：
Thompson KL
影响因子：
13.5
作者：
Isabel Lucena, M.;Andrade, Raul J.;Hidalgo, Ramon
通讯作者：
Hidalgo, Ramon
DOI：
10.1016/0272-0590(85)90100-9
发表时间：
1985-01-01
期刊：
FUNDAMENTAL AND APPLIED TOXICOLOGY
影响因子：
--
作者：
CAMERON, TP;HICKMAN, RL;TARONE, RE
通讯作者：
TARONE, RE
影响因子：
29.4
作者：
Andrade, RJ;Lucena, MI;Martin-Vivaldi, R
通讯作者：
Martin-Vivaldi, R
影响因子：
29
作者：
Gachon, Federic;Olela, Fabienne Fleury;Schibler, Ueli
通讯作者：
Schibler, Ueli