Genes and Gene Networks Involved in Sodium Fluoride-Elicited Cell Death Accompanying Endoplasmic Reticulum Stress in Oral Epithelial Cells

International Journal of Molecular Sciences

Yoshiaki Tabuchi²  Tatsuya Yunoki¹  Nobuhiko Hoshi³  Nobuo Suzuki⁴ 

[1] Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan; E-Mails:;Division of Molecular Genetics Research, Life Science Research Center, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan;Department of Animal Science, Graduate School of Agricultural Science, Kobe University, 1-1 Rokkodai, Kobe 657-8501, Japan; E-Mail:;Noto Marine Laboratory, Institute of Nature and Environmental Technology, Kanazawa University, Housu-gun, Ishikawa 927-0553, Japan; E-Mail:

关键词: sodium fluoride;    gene expression;    gene network;    cell death;    endoplasmic reticulum stress;    oral epithelial cell;   

DOI  :  10.3390/ijms15058959

来源: mdpi

【 摘 要 】

Here, to understand the molecular mechanisms underlying cell death induced by sodium fluoride (NaF), we analyzed gene expression patterns in rat oral epithelial ROE2 cells exposed to NaF using global-scale microarrays and bioinformatics tools. A relatively high concentration of NaF (2 mM) induced cell death concomitant with decreases in mitochondrial membrane potential, chromatin condensation and caspase-3 activation. Using 980 probe sets, we identified 432 up-regulated and 548 down-regulated genes, that were differentially expressed by >2.5-fold in the cells treated with 2 mM of NaF and categorized them into 4 groups by K-means clustering. Ingenuity^® pathway analysis revealed several gene networks from gene clusters. The gene networks Up-I and Up-II included many up-regulated genes that were mainly associated with the biological function of induction or prevention of cell death, respectively, such as Atf3, Ddit3 and Fos (for Up-I) and Atf4 and Hspa5 (for Up-II). Interestingly, knockdown of Ddit3 and Hspa5 significantly increased and decreased the number of viable cells, respectively. Moreover, several endoplasmic reticulum (ER) stress-related genes including, Ddit3, Atf4 and Hapa5, were observed in these gene networks. These findings will provide further insight into the molecular mechanisms of NaF-induced cell death accompanying ER stress in oral epithelial cells.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland