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AP-1 activation attenuates the arsenite-induced apoptotic response in human bronchial epithelial cells by up-regulating HO-1 expression

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Abstract

Arsenite is a cytotoxic reagent that has been used clinically to treat certain cancers. Although the cytotoxic mechanisms of arsenite have been investigated, the cellular mechanisms that act against arsenite damage are poorly understood. Heme oxygenase 1 (HO-1) has been implicated in cellular survival under other multiple stress conditions. Here, we show that a significant induction of HO-1 expression is present in human bronchial epithelial cells (Beas-2B) treated with lethal doses of arsenite treatment. This induction depends on the known ERK/AP1 signaling pathway. As expected, HO-1 RNAi knockdown, or ERK/AP1 inhibition, renders the Beas-2B cells more sensitive to arsenite damage. Our data thus suggest that transcriptional upregulation of HO-1 expression via a putative ERK/AP-1 pathway constitutes an inherent mechanism by which arsenite-induced apoptosis is attenuated.

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Acknowledgments

This project is supported by National Natural Science Foundation of China No. 31171342 and 31270797, and the National Key Research and Development Programs on Fundamental Sciences (973 Project) 2011CB503803 to Dr. Lun Song.

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Authors and Affiliations

  1. Department of New Drug Screening Center, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing, 210009, People’s Republic of China

    Aodengqimuge, Xiaoguang Li, Yi Li & Shengtao Yuan

  2. Department of Pathophysiology, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Beijing, 100850, People’s Republic of China

    Aodengqimuge, Shasha Liu, Sanyue Mai, Xiaoguang Li, Yi Li, Meiru Hu & Lun Song

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  1. Aodengqimuge
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  2. Shasha Liu
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  3. Sanyue Mai
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  4. Xiaoguang Li
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  5. Yi Li
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  6. Meiru Hu
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  7. Shengtao Yuan
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  8. Lun Song
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Correspondence to Lun Song.

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Aodengqimuge, Liu, S., Mai, S. et al. AP-1 activation attenuates the arsenite-induced apoptotic response in human bronchial epithelial cells by up-regulating HO-1 expression. Biotechnol Lett 36, 1927–1936 (2014). https://doi.org/10.1007/s10529-014-1560-z

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  • DOI: https://doi.org/10.1007/s10529-014-1560-z

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