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

Heejung Kim1, Yong-Nyun Kim, Hyungsoo Kim

  • 1Department 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.

Oncogene
|December 14, 2004
PubMed

Insights

Oxidative stress, triggered by hydrogen peroxide (H2O2), upregulates Bfl-1 expression via NF-kappaB activation. This mechanism protects cells from apoptosis, revealing a crucial cellular survival pathway.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Immunology

Background:

  • Mammalian cells produce reactive oxygen species (ROS) for various functions, including apoptosis modulation.
  • The precise relationship between ROS and apoptosis, and ROS signaling pathways, are not fully understood.

Purpose of the Study:

  • To investigate the role of ROS in apoptosis regulation.
  • To elucidate the signaling mechanisms linking ROS to apoptosis.
  • To identify specific genes involved in ROS-mediated apoptosis modulation.

Main Methods:

  • Treatment of Jurkat cells with hydrogen peroxide (H2O2) and anti-Fas antibody.
  • Analysis of Bcl-2 family gene expression patterns.
  • Inhibition studies using antioxidants and NF-kappaB inhibitors.
  • Electromobility shift assays (EMSA) to assess NF-kappaB binding to the bfl-1 promoter.
  • Experiments with Bfl-1 knockdown Jurkat cells.

Main Results:

  • H2O2 treatment impaired Fas-mediated apoptosis in Jurkat cells.
  • H2O2 specifically upregulated Bfl-1 gene expression, an antiapoptotic protein.
  • NF-kappaB activation was identified as the mediator of H2O2-induced Bfl-1 expression.
  • NF-kappaB subunits (p65/p50) bound to the bfl-1 promoter.
  • Antioxidants and NF-kappaB inhibition blocked H2O2's antiapoptotic effect and Bfl-1 induction.
  • Bfl-1 knockdown abrogated the antiapoptotic effects of H2O2.

Conclusions:

  • Oxidative stress induces Bfl-1 expression through NF-kappaB activation.
  • Upregulated Bfl-1 acts as an antiapoptotic factor, protecting cells from Fas-mediated apoptosis.
  • This pathway represents a cellular survival mechanism against ROS, potentially relevant in immune responses.

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