p38 Is a Key Signaling Molecule for H-ras-Induced Inhibition of Gap Junction Intercellular Communication in Rat Liver Epithelial Cells

doi:10.1196/annals.1329.032

^bDepartment of Food Science and Technology, School of Agricultural Biotechnology, Seoul National University, Seoul 151-742, South Korea
^cDepartment of Veterinary Public Health, College of Veterinary Medicine, Seoul National University, Seoul 151-742, South Korea

^aAddress for correspondence: Hyong Joo Lee, Department of Food Science and Technology, School of Agricultural Biotechnology, Seoul National University, Seoul 151-742, South Korea. Voice: +82-2-880-4853; fax: +82-2-873-5095. e-mail: leehyjo{at}snu.ac.kr

Multiple lines of evidence indicate that inhibition of gap junctionintercellular communication (GJIC) is a major carcinogenic process.Several reports suggest that activation of extracellular signal-regulatedprotein kinases 1 and 2 (ERK1/2) plays a key role in the disruptedGJIC by hydrogen peroxide, 12-O-tetradecanoylphorbol-13-acetate,and quinones in rat liver epithelial cells. Recently, we reportedthat p38 mitogen-activated protein kinase (MAPK) is also involvedin the inhibition of GJIC by hydrogen peroxide in WB-F344 ratliver epithelial cells (WB cells). The present study investigatedthe role of ERK1/2 and p38 MAPK in H-ras-induced inhibitionof GJIC in WB cells. H-ras induces complete inhibition of GJICand unphosphorylation of connexin 43 (Cx43) in WB cells. SB203580,an inhibitor of p38, restored inhibition of GJIC and blockedunphosphorylation of Cx43 in H-ras-transformed WB cells. However,PD98059, an inhibitor of ERK1/2, had no effect. Our resultssuggest that the disruption of GJIC induced by H-ras may bestrongly related to the unphosphorylation of Cx43 via the activationof p38 but not ERK1/2. Thus, p38 is a key signaling moleculefor H-ras-induced inhibition of GJIC in WB cells.

				Z. Wu, T. W. Lauer, A. Sick, S. F. Hackett, and P. A. Campochiaro Oxidative Stress Modulates Complement Factor H Expression in Retinal Pigmented Epithelial Cells by Acetylation of FOXO3 J. Biol. Chem., August 3, 2007; 282(31): 22414 - 22425. [Abstract] [Full Text] [PDF]