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Oxidative stress attenuates Fas-mediated apoptosis in Jurkat T cell line through Bfl-1 induction

Oncogene volume 24, pages 1252–1261 (2005)Cite this article

Abstract

Many types of mammalian cells produce ROS in response to many different stimuli to modulate a number of cellular functions, including apoptosis. However, the correlation between ROS and apoptosis remains controversial, and the mechanisms whereby ROS-induced signals are propagated to critical downstream targets remain largely undefined. Here, we demonstrate that hydrogen peroxide (H2O2) upregulates the expression of Bfl-1, an antiapoptotic member of the Bcl-2 family, and that this is responsible for the antiapoptotic activity of ROS. When Jurkat, human leukemic T cells, were pretreated with 100 μ M H2O2 and then treated with anti-Fas antibody, apoptosis was impaired without change of cell surface Fas expression. An investigation of the expression patterns of Bcl-2 family genes revealed that H2O2 treatment induced Bfl-1 gene expression, but left other genes unchanged, and this Bfl-1 expression and H2O2-induced antiapoptotic effect was inhibited by antioxidants or NF-κB inhibitor. In addition, an electromobility shift assay revealed that the p65/p50 subunits of NF-κB activated by H2O2 bound to a bfl-1 promoter. Neither the induction of Bfl-1 nor the antiapoptotic effect of H2O2 was detected in Bfl-1-knockdown Jurkat cell line containing Bfl-1 antisense (Bfl-1AS). These data indicate that oxidative stress induces the expression of Bfl-1 via NF-κB activation, and this early-response gene protects cells from Fas-mediated apoptosis. This may be a cellular survival mechanism of cells exposed to phagocytes-derived ROS.

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Acknowledgements

This work was supported by the Korea Science & Engineering Foundation (KOSEF) through the Tumor Immunity Medical Research Center at Seoul National University College of Medicine.

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Authors and Affiliations

  1. Department of Pathology, Tumor Immunity Medical Research Center and Cancer Research Institute, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul, 110-799, Korea

    Heejung Kim, Yong-Nyun Kim & Chul-Woo Kim

  2. Department of Biochemistry and Molecular Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea

    Hyungsoo Kim

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Correspondence to Chul-Woo Kim.

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Kim, H., Kim, YN., Kim, H. et al. Oxidative stress attenuates Fas-mediated apoptosis in Jurkat T cell line through Bfl-1 induction. Oncogene 24, 1252–1261 (2005). https://doi.org/10.1038/sj.onc.1208282

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