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Hydrogen peroxide activation of ERK5 confers resistance to Jurkat cells against apoptosis induced by the extrinsic pathway.

ABSTRACT: Reactive oxygen species (ROS) including hydrogen peroxide (H?O?) exhibit both pro-survival and pro-death signaling in leukemic cells. We examined the effect of exogenous H?O? on Fas ligand (FasL) -induced apoptosis in Jurkat cells. H?O? applied prior to (pre-conditioning) and during (post-conditioning) FasL stimulation attenuated early apoptosis through activation of EKR5. H?O? 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 H?O?. 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.

SUBMITTER: Suzuki T

PROVIDER: S-EPMC3974591 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Hydrogen peroxide activation of ERK5 confers resistance to Jurkat cells against apoptosis induced by the extrinsic pathway.

Suzuki Takeshi T Yang Jay J

Biochemical and biophysical research communications 20140122 2

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 a ...[more]

PMID: 24462874

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Project description:Thiol proteins are important in cellular antioxidant defenses and redox signalling. It is postulated that reactive oxidants cause selective thiol oxidation, but relative sensitivities of different cell proteins and critical targets are not well characterized. We exposed Jurkat cells to H2O2 for 10 min and measured changes in reversibly oxidized proteins by labelling with iodoacetamidofluorescein and two-dimensional electrophoresis. At 200 microM H2O2, which caused activation of the MAP (mitogen-activated protein) kinase ERK (extracellular-signal-regulated kinase), growth arrest and apoptosis, relatively few changes were seen. A total of 28 spots were reversibly oxidized (increased labelling intensity) and 24 decreased. The latter included isoforms of peroxiredoxins 1 and 2, which were irreversibly oxidized. Oxidation of GAPDH (glyceraldehyde-3-phosphate dehydrogenase) was striking, and other affected proteins included glutathione S-transferase P1-1, enolase, a regulatory subunit of protein kinase A, annexin VI, the mitotic checkpoint serine/threonine-protein kinase BUB1beta, HSP90beta (heat-shock protein 90beta) and proteosome components. At 20 microM H2O2, changes were fewer, but GAPDH and peroxiredoxin 2 were still modified. Dinitrochlorobenzene treatment, which inhibited cellular thioredoxin reductase and partially depleted GSH, caused reversible oxidation of several proteins, including thioredoxin 1 and peroxiredoxins 1 and 2. Most changes were distinct from those with H2O2, and changes with H2O2 were scarcely enhanced by dinitrochlorobenzene. Relatively few proteins, including deoxycytidine kinase, nucleoside diphosphate kinase and a proteosome activator subunit, responded only to the combined treatment. Thus most of the effects of H2O2 were not linked to thioredoxin oxidation. Our study has identified peroxiredoxin 2 and GAPDH as two of the most oxidant-sensitive cell proteins and has highlighted how readily peroxiredoxins undergo irreversible oxidation.

Dataset Information

Hydrogen peroxide activation of ERK5 confers resistance to Jurkat cells against apoptosis induced by the extrinsic pathway.

Publications

Hydrogen peroxide activation of ERK5 confers resistance to Jurkat cells against apoptosis induced by the extrinsic pathway.

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