2,3,7,8-Tetrachlorodibenzo-p-dioxin activates ERK and p38 mitogen-activated protein kinases in RAW 264.7 cells.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a widespread environmental contaminant, exposure to it eliciting a broad spectrum of deleterious pathophysiological effects. Since mitogen-activated protein kinase (MAPK) pathways appear to play an important role in both cell survival and the apoptotic process, we assessed the effects of TCDD on the activation of extracellular signal-regulated kinase (ERK), Jun-N-terminal kinase (JNK), p38 MAPKs and caspase-3 in RAW 264.7 cells. TCDD treatment induced a transient upshift in ERK activity, followed by a decline, but a concomitant dramatic activation of p38. However, TCDD did not cause any apparent change in the activity of JNK, though it induced an up-regulation in caspase-3 activity. These results demonstrate that the equilibrium between the ERK and p38 pathways is critical to the fate of the cells, and that the activation of p38, upstream of caspase, plays an important role in the apoptotic process. The data obtained in this study also suggests that TCDD activates the MAPK pathway via an arylhydrocarbon receptor (AhR)-independent mechanism in RAW 264.7 murine macrophages.
Park
Sang-Joon
SJ
Department of Veterinary Medicine, College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Korea.
Yoon
Won-Kee
WK
Kim
Ho-Jun
HJ
Son
Hwa-Young
HY
Cho
Sung-Whan
SW
Jeong
Kyu-Shik
KS
Kim
Tae-Hwan
TH
Kim
Sung-Ho
SH
Kim
Se-Ra
SR
Ryu
Si-Yun
SY
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004785:Environmental Pollutants / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D051379:Mice; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases