Identification of genetic networks involved in the cell injury accompanying endoplasmic reticulum stress induced by bisphenol A in testicular Sertoli cells.
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 (200muM) 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.
Tabuchi
Yoshiaki
Y
Division of Molecular Genetics Research, Life Science Research Center, University of Toyama, Toyama, Japan. ytabu@cts.u-toyama.ac.jp
Takasaki
Ichiro
I
Kondo
Takashi
T
D000818:Animals; D001559:Benzhydryl Compounds; D002460:Cell Line; D002470:Cell Survival; D016000:Cluster Analysis; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D008297:Male; D051379:Mice; D018832:Molecular Chaperones / Q000096:biosynthesis; D020411:Oligonucleotide Array Sequence Analysis; D010636:Phenols / Q000494:pharmacology*; D012708:Sertoli Cells / Q000378:metabolism*; D013737:Testis / Q000166:cytology*; D051742:Transcription Factor CHOP / Q000096:biosynthesis; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D010636:Phenols; D051742:Transcription Factor CHOP; C000717248:Hspa5 protein, mouse; C006780:bisphenol A; D000098826:Bisphenol A Compounds