The Role of Aryl Hydrocarbon Receptor in Histone Acetylation.

• Main Authors: Yu-Wei Chang, 張育葦
• Other Authors: Jaw-Jou Kang
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/76314102704290058770

碩士 === 國立臺灣大學 === 毒理學研究所 === 102 === Histone deacetylases (HDACs) are a class of enzymes that remove acetyl groups from histones, especially from the ε-amino group of lysine, leading the condensation of chromatin and repressing gene expression. The functions of HDACs, including migration, angiogenesis, cell differentiation, proliferation and apoptosis, have been published in many studies. It has been widely demonstrated that the abnormal acetylation of histones, causing from highly active of HDACs, would be related to many diseases, such as cancers and Rubinstein-Taybi Syndrome. In recent years, the medical developments of HDAC inhibitors are becoming common; in the view of this, we used gastric cancer cells treated a novel HDAC inhibitor, AzP, to observe the influences of this compound in vitro. In this study, the results showed that AzP increases histone acetylation and protein kinase Cα (PKCα) phosphorylation through affects sodium/calcium exchanger and raises the cytoplasmic and membrane fraction which indicates that PKCα activity increase; on the other hand, AzP induces the aryl hydrocarbon receptor (AhR) both in mRNA level and protein expression which exists in cytoplasm and nucleus. Besides, in the view of present studies, those studies indicated that PKCα would affect transcriptional factor, NF-κB, expression, and NF-κB plays a role in AhR biosynthesis. Thus, we used NF-κB inhibitor to inhibit NF-κB activity, and found that AzP-induced AhR expression was not changed, meaning that AzP did not affect AhR expression via NF-κB. Moreover, the result of promoter activity assay showed that AzP might influence the 250 to 100 bps upstream from start codon. Interestingly, we also found that repressing of AhR expression by RNA interference leads histone acetylation decreased in AzP-treated group, indicating that AhR plays a role in histone acetylation. Furthermore, the result of immunoprecipitation pointed out AzP increases protein-protein interaction between AhR and histone 2B, suggesting that AhR might has unclear functions in histone acetylation.