@article{APS4677,
author = {Qiang-song Tong and Li-duan Zheng and Shao-tao Tang and Guo-song Jiang and Qing-lan Ruan and Fu-qing Zeng and Ji-hua Dong},
title = {Nitrofen suppresses cell proliferation and promotes mitochondria-mediated apoptosis in type II pneumocytes},
journal = {Acta Pharmacologica Sinica},
volume = {28},
number = {5},
year = {2016},
keywords = {},
abstract = {Aim: To characterize the molecular mechanisms of nitrofen-induced pulmonary hypoplasia.
Methods: After administration of nitrofen to cultured type IIA549 pneumocytes, cell proliferation and DNA synthesis were investigated by 3- (4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide colorimetry, colony formation assay, flow cytometry and [3H]-thymidine incorporation assay. Apoptosis was measured by terminal transferase-mediated dUTP nick-end-labeling, acridine orange-ethidium bromide staining and flow cytometry. Expression of proliferating cell nuclear antigen (PCNA) and apoptosis-related genes was assayed by immunofluorescence, RT-PCR and Western blot.
Results: Nitrofen inhibited the cell proliferation of A549 cells in a dose- and time-dependent manner, accompanied by downregulation of PCNA. As a result, the DNA synthesis of nitrofentreated A549 cells decreased, while cell cycle was arrested at G0/G1 phase. Moreover, nitrofen induced apoptosis of A549 cells, which was not abolished by Z-Val-Ala-Asp(OCH3)- fluoromethylketone. In addition, nitrofen decreased the expression of Bcl-xL, but not of Bcl-2, Bax, and Bak, resulting in a loss of mitochondrial membrane potential and the nuclear translocation of apoptosis-inducing factor (AIF). Meanwhile, nitrofen strongly activated the p38 mitogen-activated protein kinase (p38-MAPK). Pretreatment of cells with SB203580 (5 μmol/L) blocked nitrofen-induced phosphorylation of p38-MAPK and abolished nitrofen-induced AIF translocation and apoptosis in A549 cells.
Conclusion: Nitrofen suppresses the proliferation of cultured type II pneumocytes accompanied by the downregulation of PCNA, and induces mitochondria-mediated apoptosis involving the activation of p38-MAPK.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/4677}
}