期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 444, 期 2, 页码 248-253出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2014.01.058
关键词
Apoptosis; Extrinsic pathway; Hydrogen peroxide; Jurkat cell; FAS ligand
资金
- Bamforth Endowment of the Department of Anesthesiology, UW Madison
- NIH [RO1GM071485]
Reactive oxygen species (ROS) including hydrogen peroxide (H2O2) exhibit both pro-survival and pro-death signaling in leukemic cells. We examined the effect of exogenous H2O2 on Fas ligand (FasL) -induced apoptosis in Jurkat cells. H2O2 applied prior to (pre-conditioning) and during (post-conditioning) FasL stimulation attenuated early apoptosis through activation of EKR5. H2O2 increased the activated caspase-8 sequestered in the mitochondria thereby decreasing cell death through the extrinsic apoptotic pathway. In addition, inhibition of a protein tyrosine phosphatase likely explains the post-conditioning requirement for H2O2. Given that chemotherapeutic agents used for the treatment of acute lymphoblastic leukemia are thought to work partly through production of ROS, a simultaneous inhibition of the ERK5 pathway may abrogate the ROS-initiated pro-survival signaling for an enhanced cell kill. (C) 2014 Elsevier Inc. All rights reserved.
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