Oxidative stress induces PKR-dependent apoptosis via IFN-γ activation signaling in Jurkat T cells

• Published in: Biochemical and biophysical research communications 2008-12, Vol.377 (3), p.1001-1006
• Main Authors: Pyo, Chul-Woong, Lee, Shin-Hee, Choi, Sang-Yun
• Format: Article
• Language: English
• Subjects: Apoptosis; Apoptosis - genetics; eIF-2 Kinase - antagonists & inhibitors; eIF-2 Kinase - genetics; Gene Expression - drug effects; Humans; Hydrogen Peroxide - pharmacology; Interferon; Interferon-gamma - genetics; Janus Kinase 2 - antagonists & inhibitors; Janus Kinase 2 - metabolism; Jurkat Cells; Lymphocyte Activation; Oxidative Stress - genetics; PKR; Promoter Regions, Genetic - drug effects; Protein Kinase Inhibitors - pharmacology; Reactive Oxygen Species - metabolism; RNA, Small Interfering - genetics; ROS; Signal Transduction - drug effects; T-Lymphocytes - drug effects; T-Lymphocytes - enzymology; T-Lymphocytes - immunology; Transcription, Genetic; Transcriptional Activation; Tyrphostins - pharmacology
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2008.10.103

The dsRNA-dependent protein kinase, PKR, is a central component in antiviral defense. The biological importance of PKR is further remarked by its critical role in apoptosis induced by a variety of stresses. Here, we analyzed the implication of oxidative stress in the induction of PKR-dependent apoptosis in Jurkat cells. Our results revealed that reactive oxygen species (ROS) induced endogenous pkr gene expression at the transcriptional level by activating the interferon (IFN)-γ gene. However, IFN-γ siRNA expression abrogated the H 2O 2-mediated pkr induction. The radical scavenger N-acetyl- l-cysteine profoundly inhibited pkr induction via the reduction of IFN-γ expression. The treatment of cells with the specific JAK–STAT inhibitor, AG490, reduced the PKR expression, and suppressed PKR-dependent cell death. Finally, siRNA-mediated depletion of IFN-γ or pkr efficiently downregulated H 2O 2-mediated apoptotic cell death. These results indicated that oxidative stress induces PKR expression essentially via the IFN-γ activation signal, and causes apoptosis in Jurkat T cells.