Oxidative stress induces PKR-dependent apoptosis via IFN-gamma activation signaling in Jurkat T cells.
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)-gamma gene. However, IFN-gamma siRNA expression abrogated the H(2)O(2)-mediated pkr induction. The radical scavenger N-acetyl-l-cysteine profoundly inhibited pkr induction via the reduction of IFN-gamma 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-gamma or pkr efficiently downregulated H(2)O(2)-mediated apoptotic cell death. These results indicated that oxidative stress induces PKR expression essentially via the IFN-gamma activation signal, and causes apoptosis in Jurkat T cells.
Pyo
Chul-Woong
CW
School of Life Sciences and Biotechnology, Korea University, 5 Anam-dong, Sungbuk-gu, Seoul 136-701, Republic of Korea.
Lee
Shin-Hee
SH
Choi
Sang-Yun
SY
D017209:Apoptosis / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007371:Interferon-gamma / Q000235:genetics*; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D018384:Oxidative Stress / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D020032:Tyrphostins / Q000494:pharmacology; D019892:eIF-2 Kinase / Q000037:antagonists & inhibitors / Q000235:genetics*
D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D007371:Interferon-gamma; D006861:Hydrogen Peroxide; D053614:Janus Kinase 2; D019892:eIF-2 Kinase