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 H2O2-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 H2O2-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.
|Number of pages||6|
|Journal||Biochemical and biophysical research communications|
|Publication status||Published - 2008 Dec 19|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology