Indole-3-Carbinol Prevents H2O 2-Induced Inhibition of Gap Junctional Intercellular Communication by Inactivation of PKB/Akt

Journal of Veterinary Medical Science

Jae-Woong HWANG¹  Kyung-Sun KANG¹  Ji-Won JUNG¹  Yong-Soon LEE¹ 

[1] Laboratory of Stem Cell and Tumor Biology, Department of Veterinary Public Health, College of Veterinary Medicine, Seoul National University

关键词: gap junctional intercellular communication;    indole-3-carbinol;    oxidative stress;    PKB/Akt;   

DOI  :  10.1292/jvms.70.1057

学科分类：兽医学

来源: Japanese Society of Veterinary Science

【 摘 要 】

References(46)Cited-By(4)Indole-3-carbinol (I3C) is a phytochemical found in cruciferous vegetables and possesses a variety of biological and biochemical effects. Despite a wealth of data about the chemopreventive properties of I3C, its effects on gap junctional intercellular communication (GJIC), which is associated with the promotion and progression phases of the multi-stage process of carcinogenesis, has not been studied. In this study, we examined the ability of I3C to prevent H2O 2-induced inhibition of GJIC in WB-F344 rat liver epithelial cells (WB cells). The cells were preincubated with I3C for 48 hr, and then treated with 1 mM H2O2 for 1 hr. We found that I3C could prevent the H2O2-induced inhibition of GJIC through prevention of the phosphorylated state of gap junction protein connexin 43 (Cx43) phosphorylation. Prevention of GJIC by I3C was dependent upon inactivation of Akt, but not MAPK, although inhibition of GJIC by H2O2 leads to activation of both. Similar to I3C, modulation of Akt activation through the phosphoinositide-3 kinase inhibitor, LY294002, could also prevent H2O2-induced inhibition of GJIC and phosphorylation of Cx43. Our results suggest that I3C might exert its dietary chemopreventive effects by interfering with the Akt signaling pathway, which appears to be linked to modulating GJIC, a cellular mechanisms regulating cell proliferation, differentiation and apoptosis.

【 授权许可】

Unknown