S-Space College of Veterinary Medicine (수의과대학) Dept. of Veterinary Medicine (수의학과) Journal Papers (저널논문_수의학과)
Effects of the histone deacetylases inhibitors sodium butyrate and trichostatin A on the inhibition of gap junctional intercellular communication by H2O2- and 12-O-tetradecanoylphorbol-13-acetate in rat liver epithelial cells
- Jung, Ji-Won; Cho, Sung-Dae; Ahn, Nam-Shik; Yang, Se-Ran; Park, Joon-Suk; Jo, Eun-Hye; Hwang, Jae-Woong; Aruoma, Okezie I.; Lee, Yong Soon; Kang, Kyung-Sun
- Issue Date
- Cancer Lett. 241 (2006) 301–308
- Histone deacetylase inhibitor; Sodium butyrate; Trischostatin A; Gap junctional intercellular communication; Rat liver; Cancer promotion
- The histone deacetylase (HDAC) inhibitors, trichostatin A (TSA) and sodium butyrate (NaBu) are considered as potent therapeutic agents for cancer treatment presenting therapeutic benefits with less risk of side effects. The microbial metabolite, TSA is a potent reversible and highly specific inhibitor of mammalian histone deacetylases. NaBu causes hyperacetylation of core histones with effects similar to TSA but it is not a specific inhibitor of HDACs. The gap junction is a channel in the plasma membrane of most cell types which allows direct communication (gap junctional intercellular communication; GJIC) of small molecules and ions. Modulation of GJIC is a known cellular event associated with tumor promotion. The effects of NaBu and TSA on the H2O2- and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced GJIC inhibition of WB cells and the mechanisms involved in the process were assessed. TSA and NaBu exerted differential preventive effects on the H2O2 and TPA-induced inhibition of GJIC as well as hyperphosphorylation of connexin43 (Cx43) in WB-F344 rat liver epithelial cells (WB cells). NaBu prevented the TPA-induced GJIC inhibition via ERK1/2 inactivation whilst TSA restored the H2O2-induced GJIC inhibition and Cx43 hyperphosphorylation by preventing p38 MAP kinase. The inhibition of tyrosine phosphorylation and down-regulation of src protein observed may also contribute to Connexin 43 dephosphorylation and GJIC restoration by TSA and NaBu partly through depletion of src protein pool. Thus, TSA and NaBu exert differential effects on chemically induced GJIC inhibition via modulation of MAP kinases and partly, tyrosine kinases.
- Files in This Item: There are no files associated with this item.