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Activation of JNK and c-Jun Is Involved in Glucose Oxidase-Mediated Cell Death of Human Lymphoma Cells

  • Son, Young-Ok (Graduate Center for Toxicology, University of Kentucky) ;
  • Jang, Yong-Suk (Department of Bioactive Material Sciences and Research Center of Bioactive Materials, Chonbuk National University) ;
  • Shi, Xianglin (Graduate Center for Toxicology, University of Kentucky) ;
  • Lee, Jeong-Chae (Department of Bioactive Material Sciences and Research Center of Bioactive Materials, Chonbuk National University)
  • Received : 2009.07.13
  • Accepted : 2009.09.17
  • Published : 2009.12.31

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 ($H_2O_2$)-induced cell death are unclear. This study examined the effects of $H_2O_2$ on the activation of MAPK and AP-1 by exposing the cells to $H_2O_2$ generated by either glucose oxidase or a bolus addition. Exposing BJAB or Jurkat cells to $H_2O_2$ affected the activities of MAPK differently according to the method of $H_2O_2$ exposure. $H_2O_2$ increased the AP-1-DNA binding activity in these cells, where continuously generated $H_2O_2$ led to an increase in mainly the c-Fos, FosB and c-Jun proteins. The c-Jun-$NH_2$-terminal kinase (JNK)-mediated activation of c-Jun was shown to be related to the $H_2O_2$-induced cell death. However, the suppression of $H_2O_2$-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 $H_2O_2$. This was associated with the disruption of death signaling according to the severe and prolonged depletion of reduced glutathione. Overall, these results suggest that $H_2O_2$ 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 $H_2O_2$ than the concentration of this agent.

Keywords

Acknowledgement

Supported by : Korea Science and Engineering Foundation

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