NUCLEAR FACTOR-κB MEDIATES CYTOPROTECTION OF HYDROGEN PEROXIDE PRECONDITIONING AGAINST APOPTOSIS INDUCED BY OXIDATIVE STRESS IN PC12 CELLS

作者:Zhang, Mei; Guo, Rui-Xian; Mo, Li-Qiu; Liao, Xin-Xue; Li, Wei; Zhi, Jun-Li; Sun, Sheng-Nan; Wang, Yan-Li; Cui, Yu; Liu, Wei; Feng, Jian-Qiang*; Chen, Pei-Xi
来源:CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 2009, 36(3): 304-311.
DOI:10.1111/j.1440-1681.2008.05066.x

摘要

1. Cytoprotection by H2O2 preconditioning against oxidative stress-induced apoptosis of PC12 cells has been demonstrated previously. In the present study, we investigated the effects of H2O2 preconditioning on nuclear factor (NF)-kappa B activation and the role of NF-kappa B in the adaptive cytoprotection of H2O2 preconditioning in PC12 cells. @@@ 2. The PC12 cells were preconditioned with 100 mu mol/L H2O2 for 90 min, followed by 24 h recovery and subsequent exposure to 300 mu mol/L H2O2 for a further 12 h. @@@ 3. The results showed that preconditioning with 100 mu mol/L H2O2 upregulated NF-kappa B expression and enhanced its nuclear translocation and DNA binding activity. In addition to its own effects on NF-kappa B expression, H2O2 preconditioning also promoted the overexpression of NF-kappa B induced by a lethal concentration of H2O2 (300 mu mol/L). @@@ 4. N-Tosyl-L-phenylalanine chloromethyl ketone (TPCK; 20 mu mol/L), an inhibitor of NF-kappa B, was administered 20 min before preconditioning with 100 mu mol/L H2O2. At this concenteration, TPCK blocked the overexpression of NF-kappa B induced by H2O2 preconditioning, accompanied by attenuation of H2O2 preconditioning-induced cytoprotection. The inhibition of NF-kappa B by TPCK enhanced caspase 3 activity induced by 300 mu mol/L H2O2. @@@ 5. The findings of the present study provide novel evidence for the effects of preconditioning with H2O2 on constitutive activation of NF-kappa B, which contributes to the adaptive cytoprotection of H2O2 preconditioning against PC12 cells apoptosis.