Activation of mitogen activated protein kinases by PCB126 (3,3',4,4',5-pentachlorobiphenyl) in HepG2 cells.
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.
Song
Min Ok
MO
Nicholas School of the Environment and Earth Sciences, Duke University, Durham, North Carolina 27708-0328, USA.
Freedman
Jonathan H
JH
D000975:Antioxidants / Q000378:metabolism; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004965:Estrogen Antagonists / Q000633:toxicity*; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis*; D018384:Oxidative Stress; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D020218:Response Elements; D018808:Transcription Factor AP-1 / Q000378:metabolism
D000975:Antioxidants; D004965:Estrogen Antagonists; D018808:Transcription Factor AP-1; D011078:Polychlorinated Biphenyls; D020928:Mitogen-Activated Protein Kinases; C023035:3,4,5,3',4'-pentachlorobiphenyl