Activation of JNK and c-Jun is involved in glucose oxidase-mediated cell death of human lymphoma cells
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Mitogen-activated protein kinases (MAPK) affect the activation of activator protein-1 (AP-1), which plays an important role in regulating a range of cellular processes. However, the roles of these signaling factors on hydrogen peroxide (H2O2)-induced cell death are unclear. This study examined the effects of H2O2 on the activation of MAPK and AP-1 by exposing the cells to H2O2 generated by either glucose oxidase or a bolus addition. Exposing BJAB or Jurkat cells to H2O2 affected the activities of MAPK differently according to the method of H2O2 exposure. H2O2 increased the AP-1-DNA binding activity in these cells, where continuously generated H2O2 led to an increase in mainly the c-Fos, FosB and c-Jun proteins. The c-Jun-NH2-terminal kinase (JNK)-mediated activation of c-Jun was shown to be related to the H2O2-induced cell death. However, the suppression of H2O2-induced oxidative stress by either JNK inhibitor or c-Jun specific antisense transfection was temporary in the cells exposed to glucose oxidase but not to a bolus H2O2. This was associated with the disruption of death signaling according to the severe and prolonged depletion of reduced glutathione. Overall, these results suggest that H2O2 may decide differently the mode of cell death by affecting the intracellular redox state of thiol-containing antioxidants, and this depends more closely on the duration exposed to H2O2 than the concentration of this agent.
Keywordsactivator protein-1 antioxidant defense enzymes human lymphoma cells hydrogen peroxide mitogen-activated protein kinase
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