Induced proliferation of human MRC-5 cells by nitrogen oxides via direct and indirect activation of MEKK1, JNK, and p38 signals.
Nitrogen oxides (NOx) are important indoor air pollutants and an occupational hazard. Many studies demonstrated that NOx causes lung tissue damage based on the oxidation properties and the free-radical potentials of these gases. In this study we found that NOx delivered as a NO gas-saturated solution induced proliferation of human lung fibroblast MCR-5 cells as evidenced by increasing cell number and S phase distribution. Western data showed that NOx increased the expressions of c-Fos, c-Jun, and signaling kinases including MEKK1, JNK1, and p38 (with induction fold of 3.3, 2.8, and 3.2, respectively) in the cells 12 h after treatment. The levels of phospho-MEKK1 and phospho-JNK1 were also increased. The application of iNOS inhibitor, NAME, partially blocked the activation of MEKK4 and JNK1. These data suggested that JNK and p38 signaling kinases are activated partly by endogenous NO that are generated from NOx-activated iNOS in MRC-5 cells. Therefore, the NOx-induced cell proliferation via activation of MEKK1, JNK1, and p38 might contribute to lung tissue damage caused by NOx pollutants.
Chou
Fen-Pi
FP
Institute of Biochemistry, Chung Shan Medical University, Taichung, Taiwan.
Tseng
Tsui-Hwa
TH
Chen
Jing-Hsien
JH
Wang
Hsue-Chun
HC
Wang
Chau-Jong
CJ
D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects; D016758:Genes, jun / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D007700:Kinetics; D008168:Lung / Q000166:cytology; D048670:MAP Kinase Kinase 4; D048728:MAP Kinase Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D009589:Nitrogen Oxides / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases
D004791:Enzyme Inhibitors; D009589:Nitrogen Oxides; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D017346:Protein Serine-Threonine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D019331:NG-Nitroarginine Methyl Ester