Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40536-0001, USA.
Mol Cells. 2009 Dec 31;28(6):545-51. doi: 10.1007/s10059-009-0149-1. Epub 2009 Nov 19.
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(2)O(2))-induced cell death are unclear. This study examined the effects of H(2)O(2) on the activation of MAPK and AP-1 by exposing the cells to H(2)O(2) generated by either glucose oxidase or a bolus addition. Exposing BJAB or Jurkat cells to H(2)O(2) affected the activities of MAPK differently according to the method of H(2)O(2) exposure. H(2)O(2) increased the AP-1-DNA binding activity in these cells, where continuously generated H(2)O(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(2)O(2)-induced cell death. However, the suppression of H(2)O(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(2)O(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(2)O(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(2)O(2) than the concentration of this agent.
丝裂原活化蛋白激酶（MAPK）影响激活蛋白-1（AP-1）的激活，AP-1 在调节多种细胞过程中起着重要作用。然而，这些信号因子在过氧化氢（H2O2）诱导的细胞死亡中的作用尚不清楚。本研究通过用葡萄糖氧化酶或一次性添加的方式产生 H2O2，来检测 H2O2 对 MAPK 和 AP-1 激活的影响。暴露 BJAB 或 Jurkat 细胞于 H2O2 中，根据 H2O2 暴露方式的不同，MAPK 的活性受到不同的影响。H2O2 增加了这些细胞中的 AP-1-DNA 结合活性，其中持续产生的 H2O2 导致 c-Fos、FosB 和 c-Jun 蛋白的增加。c-Jun-NH2-末端激酶（JNK）介导的 c-Jun 激活与 H2O2 诱导的细胞死亡有关。然而，在暴露于葡萄糖氧化酶的细胞中，通过 JNK 抑制剂或 c-Jun 特异性反义转染抑制 H2O2 诱导的氧化应激是暂时的，但在暴露于一次性 H2O2 的细胞中则不是。这与根据还原型谷胱甘肽的严重和持久耗竭而导致的死亡信号的中断有关。总的来说，这些结果表明，H2O2 可能通过影响含巯基抗氧化剂的细胞内氧化还原状态，以不同的方式决定细胞死亡的模式，而这与暴露于 H2O2 的时间长短比 H2O2 浓度更为密切相关。
