Altered function, localization and phosphorylation of gap junctions in rat liver epithelial, IAR 20, cells after
Y Bager1, M C Lindebro, P Martel
1Institute of Environmental Medicine, Karolinska Institutet, Box 210, S-171 77, Stockholm, Sweden.
Abstract:
Three different PCB-congeners 3,4,5,3',4'-pentachlorobiphenyl (IUPAC no. 126), 2,4,5,2',4',5'-hexachlorobiphenyl (IUPAC no. 153) and 2,4,5,3',4'-pentachlorobiphenyl (IUPAC no. 118) were investigated for possible structure-activity relationships in altering gap junction intercellular proteins. All tested PCB-congeners and TCDD decreased the gap junctional intercellular communication in IAR 20 cells, but at different treatment periods, suggesting different modes of action. The presence of the Cx43-P(2) band, a phosphorylated isoform of Cx43, was associated with a functional communication. A reduced Cx43 mRNA level was noted after 48 h of exposure with PCB 126, PCB 118 and TCDD. In summary, the non dioxin-like PCB 153 can decrease gap junctional intercellular communication rapidly by reducing the phosphorylated isoform of Cx43, whereas the dioxin-like PCB 126 and TCDD reduce the communication slowly by decreasing the mRNA level of Cx43, resulting in a reduced Cx43 protein level (which includes the P(2)-band). The mixed inducing PCB-congener, PCB 118, can act both as the dioxin-like and the non dioxin-like PCBs in gap junction regulation.
