Gaseous nitrogen oxide repressed benzo[a]pyrene-induced human lung fibroblast cell apoptosis via inhibiting JNK1 signals.
Benzo[a]pyrene (B[a]P) is present in environmental pollution and cigarette smoke. B[a]P has been shown to induce apoptosis in hepatoma cells, human B cells, human ectocervical cells, macrophages, and rat lungs. Nitrogen oxides (NOx) are the other important indoor and outdoor air pollutants. Many studies have indicated that NO gas causes lung tissue damage both by its oxidative properties and free radicals. In our previous study we demonstrated that NO gas induced proliferation of human lung fibroblast MRC-5 cells. In this study we showed that NO gas inhibits B[a]P-induced MRC-5 cells apoptosis by cell cycle analysis. Western blot data revealed that NO gas increased the expressions of anti-apoptosis proteins (Bcl-2 and Mcl-1) and decreased the expression of apoptosis proteins (Bax, t-Bid, cytochrome c, FasL, and caspases) after B[a]P treatment. We further clarified that B[a]P-induced MRC-5 cell apoptosis via JNK1/FasL and JNK1/p53 signals. In conclusion, NO gas inhibited B[a]P-induced MRC-5 cells apoptosis via inhibition of JNK1 apoptosis pathway and induction of Bcl-2 and Mcl-1 anti-apoptosis pathway.
Chen
Jing-Hsien
JH
Institute of Biochemistry and Biotechnology, Chung Shan Medical University, No. 110, Sec. 1, Chien Kuo N. Road, Taichung, 402 Taiwan.
Chou
Fen-Pi
FP
Lin
Hui-Hsuan
HH
Wang
Chau-Jong
CJ
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001564:Benzo(a)pyrene / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D053222:Fas Ligand Protein; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000166:cytology; D008562:Membrane Glycoproteins / Q000378:metabolism; D048055:Mitogen-Activated Protein Kinase 8 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D048069:Tumor Necrosis Factors / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D019014:fas Receptor
D051017:Apoptosis Regulatory Proteins; D002273:Carcinogens; C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; D048069:Tumor Necrosis Factors; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor; D009569:Nitric Oxide; D001564:Benzo(a)pyrene; D048055:Mitogen-Activated Protein Kinase 8