Identification of genetic networks involved in the cell injury accompanying endoplasmic reticulum stress induced by bisphenol A in testicular Sertoli cells
Identification of genetic networks involved in the cell injury accompanying endoplasmic reticulum stress induced by bisphenol A in testicular Sertoli cells
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DOI：
10.1016/j.bbrc.2006.04.177
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发表时间：
2006-07-07
影响因子：
3.1
通讯作者：
Kondo, Takashi
中科院分区：
文献类型：
--
作者：
Tabuchi, Yoshiaki;Takasaki, Ichiro;Kondo, Takashi
为了确定内分泌干扰物双酚A(BPA)诱导小鼠睾丸Sertoli TTE3细胞损伤的详细机制，我们进行了全基因组微阵列和计算基因网络分析。双酚A(200 PM)显著降低细胞存活率，同时诱导内质网应激标记基因HSPA5和DDIT3的mRNA水平升高。在分析的22,690个探针组中，BPA下调了661个探针组，上调了2.0倍的604个探针组。系统聚类分析显示有9个基因簇。在减少的基因簇中，有两个显著的遗传网络与细胞生长和增殖以及细胞周期有关。在增加的基因簇中，包括许多碱性区域亮氨酸拉链转录因子在内的两个重要的遗传网络与细胞死亡和DNA复制、重组和修复有关。本研究结果将为揭示BPA诱导的支持细胞内质网损伤的分子机制提供新的线索。(C)2006 Elsevier Inc.保留所有权利。
To identify detailed mechanisms by which bisphenol A (BPA), an endocrine-disrupting chemical, induces cell injury in mouse testicular Sertoli TTE3 cells, we performed genome-wide microarray and computational gene network analyses. BPA (200 PM) significantly decreased cell viability and simultaneously induced an increase in mRNA levels of HSPA5 and DDIT3, endoplasmic reticulum (ER) stress marker genes. Of the 22,690 probe sets analyzed, BPA down-regulated 661 probe sets and up-regulated 604 probe sets by > 2,0-fold. Hierarchical cluster analysis demonstrated nine gene clusters. In decreased gene clusters, two significant genetic networks were associated with cell growth and proliferation and the cell cycle. In increased gene clusters, two significant genetic networks including many basic-region leucine zipper transcription factors were associated with cell death and DNA replication, recombination, and repair. The present results will provide additional novel insights into the detailed molecular mechanisms of cell injury accompanying ER stress induced by BPA in Sertoli cells. (c) 2006 Elsevier Inc. All rights reserved.