Cell proliferation induced by reactive oxygen species is mediated via mitogen-activated protein kinase in Chinese hamster lung fibroblast (V79) cells.
Reactive oxygen species (ROS) are generated during cellular metabolism or by external factors. Recently, it was learned that ROS can stimulate cellular proliferation and act as a second messenger in cellular signaling. We previously reported that hydroxyl radicals might be the signaling molecules. In the present experiment, phenazine methosulfate (PMS) was used to generate superoxide anion intracellularly. Treatment with 3 microM PMS in V79 cells increased cellular proliferation by 50%. PMS also activated the c-Jun N-terminal kinase (JNK) and p38 MAPK, but not extracellular signal-regulated kinase (ERK) 1/2 and ERK5. In particular, increased proliferation was blocked by pretreatment with SB203580 (an inhibitor of p38 MAPK). At the transcriptional level, the phosphorylation of c-Jun and ATF-2, which are mediated by JNK and p38 MAPK, were also increased by treatment with PMS.
Han
Min-Joon
MJ
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
Kim
Bu-Yeo
BY
Yoon
Sang-Oh
SO
Chung
An-Sik
AS
D051698:Activating Transcription Factor 2; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D019817:Benzoic Acid / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line / Q000166:cytology / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects*; D016166:Free Radical Scavengers / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007502:Iron Chelating Agents / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D008168:Lung / Q000166:cytology; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008773:Methylphenazonium Methosulfate / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D013481:Superoxides / Q000494:pharmacology*; D014157:Transcription Factors / Q000378:metabolism; D024483:Vitamin K 3 / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases
D051698:Activating Transcription Factor 2; D000975:Antioxidants; D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D007093:Imidazoles; D007502:Iron Chelating Agents; D016755:Proto-Oncogene Proteins c-jun; D011725:Pyridines; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D013481:Superoxides; D008773:Methylphenazonium Methosulfate; D024483:Vitamin K 3; D019817:Benzoic Acid; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D003676:Deferoxamine; C093642:SB 203580