Differential regulation of the hydrogen-peroxide-induced inhibition of gap-junction intercellular communication by resveratrol and butylated hydroxyanisole.
The present study was performed to evaluate the effects of two different phenolic antioxidants, 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.
Kim
Jong Hun
JH
Major in Biomodulation, Department of Agricultural Biotechnology, Research Institute for Agriculture and Life Sciences, Seoul National University, 599 Gwangak-ro, Gwanak-gu, Seoul 151-921, Republic of Korea.
Choi
Seung Hwan
SH
Kim
Jiyoung
J
Lee
Bo Kyung
BK
Lee
Ki Won
KW
Lee
Hyong Joo
HJ
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002083:Butylated Hydroxyanisole / Q000494:pharmacology*; D002450:Cell Communication / Q000187:drug effects*; D002460:Cell Line; D018031:Connexin 43 / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D010766:Phosphorylation; D051381:Rats; D011916:Rats, Inbred F344; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*
D000975:Antioxidants; D018031:Connexin 43; D005609:Free Radicals; D013267:Stilbenes; D002083:Butylated Hydroxyanisole; D006861:Hydrogen Peroxide; D000077185:Resveratrol