Hydrogen peroxide activation of ERK5 confers resistance to Jurkat cells against apoptosis induced by the extrinsic pathway.
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.
Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53711, USA; Department of Anesthesiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Takeshi
T
Suzuki
Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53711, USA. Electronic address: jyang75@wisc.edu.
Jay
J
Yang
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053181:Caspase 8 / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D004789:Enzyme Activation / Q000187:drug effects; D053222:Fas Ligand Protein / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D019169:Jurkat Cells; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D048054:Mitogen-Activated Protein Kinase 7 / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors
D053222:Fas Ligand Protein; D016877:Oxidants; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D048054:Mitogen-Activated Protein Kinase 7; D053181:Caspase 8
Apoptosis; Extrinsic pathway; FAS ligand; Hydrogen peroxide; Jurkat cell