Journal
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
Volume 671, Issue 1-2, Pages 40-44Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.mrfmmm.2009.08.011
Keywords
BHA; Cx43; ERK; GJIC; H2O2; Resveratrol
Funding
- WCU Program [R31-2008-00-10056-0]
- Basic Research Program [R01-2007000-11957-0]
- National Research Foundation of Korea
- Ministry of Education, Science and Technology, Republic of Korea
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The present study was performed to evaluate the effects of two different phenolic antioxiclants, resveratrol (3,5,4'-trihydroxystilbene) and butylated hydroxyanisole (BHA), on the hydrogen peroxide (H2O2)-induced inhibition of gap-junction intercellular communication (GJIC) in WB-F344 rat liver epithelial cells (WB-F344). Resveratrol is a naturally occurring polyphenolic antioxidant; on the other hand, BHA is a synthetic phenolic compound. We found that only resveratrol protects WB-F344 cells from H2O2-induced inhibition of GJIC, and BHA has no effect. The extracellular-signal-regulated protein kinase 1/2 (ERK1/2)-connexin 43 (Cx43) signaling pathway is crucial for the regulation of GJIC in rat liver epithelial cells, and resveratrol, but not BHA, blocked the H2O2-induced phosphorylation of Cx43, a critical regulator of GJIC, and ERK1/2 in WB-F344 cells. Resveratrol appears to attenuate the H2O2-mediated ERK1/2-Cx43 signaling pathway and consequently reverses H2O2-mediated inhibition of GJIC. DPPH and ABTS radical-scavenging assays revealed that the protective effect of resveratrol on the H2O2-mediated inhibition of GJIC was not mediated through its free radical-scavenging activity. (C) 2009 Elsevier B.V. All rights reserved.
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