Abstract
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.
Original language | English |
---|---|
Pages (from-to) | 545-551 |
Number of pages | 7 |
Journal | Molecules and Cells |
Volume | 28 |
Issue number | 6 |
DOIs | |
State | Published - Dec 2009 |
Bibliographical note
Funding Information:This work was supported by a Grant from the Korea Science and Engineering Foundation, Republic of Korea (No. 2009-0067712).
Keywords
- Activator protein-1
- Antioxidant defense enzymes
- Human lymphoma cells
- Hydrogen peroxide
- Mitogen-activated protein kinase
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology