AP-2α expression and cell apoptosis of the lung tissue of rats with COPD and ECV304 cells stimulated by cigarette smoke extract

作者：Li JunLi; Chen Yan; Chen Ping^*; Cai Shan; Peng Hong; Zhou Rui; Xiang XuDong; Long Hong; Liu ShaoKun

来源：Chinese Science Bulletin, 2011, 56(15): 1562-1568.

DOI：10.1007/s11434-011-4437-8

• AP-2 alpha
• apoptosis
• cigarette smoke extract
• COPD
• vascular endothelial cell

An increasing body of evidence suggests that apoptosis of structural cells in the lung might be an important upstream event in the pathogenesis of chronic obstructive pulmonary disease (COPD). AP-2 alpha is one of the important transcription factors involved in the modulation of apoptosis in carcinogenesis and idiopathic-dilated cardiomyopathy. The relationship between AP-2 alpha and apoptosis in COPD remains to be elucidated. The aim of the present study was to investigate the expression of AP-2 alpha in the lung tissues of rats with COPD induced by smoking and its possible protective effect on cigarette smoke extract (CSE) induced endothelial cell apoptosis. Sprague-Dawley rats (n = 24) were randomly assigned to normal and COPD groups. The COPD group was exposed to smoke from 20 commercial unfiltered cigarettes for 80 d before morphological assessment of the lung tissue was performed. The expression of AP-2 alpha in lung tissues was measured by Western blotting. To demonstrate the relationship between apoptosis and AP-2 alpha, in vitro cell experiments were carried out. Cells were treated with different concentrations of CSE before proliferation was measured by MTT. Apoptosis was then determined by Hoechst staining and the expression of cleaved caspase-3 and AP-2 alpha by Western blotting over time following treatment with 5% CSE. Cells were then infected with an AP-2 alpha adenovirus vector and the expression of cleaved caspase-3 and AP-2 alpha was compared to the control groups by Western blotting. The COPD group showed larger air spaces and significant decrease of FEV0.3/FVC compared with the rats in the control group (P < 0.05). The expression of AP-2 alpha was significantly higher in the lung tissue of rats with COPD compared with those of controls (P < 0.05). In the ECV304 cells, CSE induced apoptosis (P < 0.01) and caspase-3 activation in a time-dependent manner and reduced the cell proliferation rate in a dose-dependent manner (P < 0.005). Moreover, 5% CSE treatment increased endogenous AP-2 alpha protein expression. AP-2 alpha overexpression inhibited 5% CSE-induced cell apoptosis and activated caspase-3 expression (P < 0.05) AP-2 alpha protects ECV304 cells against CSE-induced apoptosis and may play an important role in smoking induced-apoptosis in COPD.

• 出版日期2011-5
• 单位中南大学