Role of Foxa1 in regulation of bcl2 expression during oxidative-stress-induced apoptosis in A549 type II pneumocytes.
Forkhead box protein A1 (Foxa1) is an evolutionarily conserved winged helix transcription factor that was traditionally considered to be involved in embryonic development and cell differentiation. However, little is known about the role of Foxa1 in oxidative-stress-induced apoptosis. In this study, hydrogen peroxide (H(2)O(2))-induced apoptosis, upregulation of Foxa1, and the role of Foxa1 in the regulation of bcl2 gene expression were studied in A549 type II pneumocytes. H(2)O(2) upregulated Foxa1 mRNA and protein in a time- and dose-dependent manner. Overexpression of Foxa1 promoted apoptosis, whereas Foxa1 deficiency, induced by antisense oligonucleotides, decreased A549 cell apoptosis induced by H(2)O(2), as shown by flow cytometry. Moreover, Foxa1 overexpression decreased the expression of bcl2, while Foxa1 depletion increased the expression of bcl2. Electrophoretic mobility shift assay and chromatin immunoprecipitation revealed that Foxa1 bound to bcl2 promoter, and H(2)O(2) promoted its DNA binding activity. Luciferase reporter showed that Foxa1 also decreased the transcription activity of bcl2 promoter under normal conditions and oxidative stress. These results indicate that Foxa1 plays a pro-apoptotic role by inhibiting the expression of anti-apoptotic gene bcl2.
Song
Lan
L
Laboratory of Shock, Department of Pathophysiology, Xiangya School of Medicine, Central South University, Hunan, People's Republic of China.
Wei
Xing
X
Zhang
Bin
B
Luo
Xinjing
X
Liu
Junwen
J
Feng
Yansheng
Y
Xiao
Xianzhong
X
D017209:Apoptosis; D045744:Cell Line, Tumor; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000502:physiology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008175:Lung Neoplasms / Q000378:metabolism; D018384:Oxidative Stress; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*
C496499:FOXA1 protein, human; D051541:Hepatocyte Nuclear Factor 3-alpha; D019253:Proto-Oncogene Proteins c-bcl-2; D006861:Hydrogen Peroxide