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

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SUMMARY



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)-κB activation and the role of NF-κB in the adaptive cytoprotection of H2O2 preconditioning in PC12 cells.



The PC12 cells were preconditioned with 100 µmol/L H2O2 for 90 min, followed by 24 h recovery and subsequent exposure to 300 µmol/L H2O2 for a further 12 h.



The results showed that preconditioning with 100 µmol/L H2O2 upregulated NF-κB expression and enhanced its nuclear translocation and DNA binding activity. In addition to its own effects on NF-κB expression, H2O2 preconditioning also promoted the overexpression of NF-κB induced by a lethal concentration of H2O2 (300 µmol/L).



N-Tosyl-l-phenylalanine chloromethyl ketone (TPCK; 20 µmol/L), an inhibitor of NF-κB, was administered 20 min before preconditioning with 100 µmol/L H2O2. At this concenteration, TPCK blocked the overexpression of NF-κB induced by H2O2 preconditioning, accompanied by attenuation of H2O2 preconditioning-induced cytoprotection. The inhibition of NF-κB by TPCK enhanced caspase 3 activity induced by 300 µmol/L H2O2.

5. The findings of the present study provide novel evidence for the effects of preconditioning with H2O2 on constitutive activation of NF-κB, which contributes to the adaptive cytoprotection of H2O2 preconditioning against PC12 cells apoptosis.
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Keywords: N-tosyl-l-phenylalanine chloromethyl ketone (TPCK); cytoprotection; hydrogen peroxide preconditioning; nuclear factor-κB

Document Type: Research Article

Publication date: March 1, 2009

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