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Role of Foxa1 in regulation of bcl2 expression during oxidative-stress-induced apoptosis in A549 type II pneumocytes

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Cell Stress and Chaperones Aims and scope

Abstract

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 (H2O2)-induced apoptosis, upregulation of Foxa1, and the role of Foxa1 in the regulation of bcl2 gene expression were studied in A549 type II pneumocytes. H2O2 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 H2O2, 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 H2O2 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.

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Acknowledgments

This work was supported by funding from the National Nature Science Foundation of China (30330280), the Nature Science Foundation of Hunan Province, China (08JJ3030), and the Science Foundation of Health Department of Hunan, China (2007B090).

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Authors and Affiliations

  1. Laboratory of Shock, Department of Pathophysiology, Xiangya School of Medicine, Central South University, 110 Xiangya Road, Changsha, Hunan, 410078, People’s Republic of China

    Lan Song, Xing Wei, Bin Zhang, Xinjing Luo, Junwen liu, Yansheng Feng & Xianzhong Xiao

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  1. Lan Song
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  2. Xing Wei
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  3. Bin Zhang
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Correspondence to Xianzhong Xiao.

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Song, L., Wei, X., Zhang, B. et al. Role of Foxa1 in regulation of bcl2 expression during oxidative-stress-induced apoptosis in A549 type II pneumocytes. Cell Stress and Chaperones 14, 417–425 (2009). https://doi.org/10.1007/s12192-008-0095-4

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  • DOI: https://doi.org/10.1007/s12192-008-0095-4

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