Activation of Mitogen Activated Protein Kinases by PCB126 (3,3',4,4',5-Pentachlorobiphenyl) in HepG2 Cells

Abstract

Polychlorinated biphenyls (PCBs) are persistent organic pollutants. Exposure to PCB126 (3,3',4,4',5-pentachlorobiphenyl), a non-ortho-chlorinated, coplanar congener has been correlated with the production of reactive oxygen species in vivo. In this report, we show that treatment of HepG2 cells with PCB126 significantly increases oxidative-stress-responsive transcription. In addition, PCB126-induced transcription is enhanced in cells depleted of glutathione. Exposure to PCB126 induces a cellular stress response in HepG2 cells that results in a significant increase in the activity of the mitogen activated protein kinases: extracellular signal regulated kinases 1/2 and p38. PCB126 exposure also causes an increase in c-Jun phosphorylation. These results suggest a model for PCB126 toxicity in which PCB126 exposure induces oxidative stress that causes an increase in mitogen-activated protein kinase (MAPK) activities and a subsequent increase in c-Jun phosphorylation. Activation of c-Jun results in enhanced activating protein-1 (AP-1) activity, which leads to elevated expression of antioxidant responsive element (ARE)/AP-1-dependent genes.