Activation of JNK and c-Jun is involved in glucose oxidase-mediated cell death of human lymphoma cells

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 H ₂O₂ 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 H₂O ₂-induced cell death. However, the suppression of H₂O ₂-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 H₂O ₂ 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.