Nuclear factor-kappaB mediates cytoprotection of hydrogen peroxide preconditioning against apoptosis induced by oxidative stress in PC12 cells.
1. Cytoprotection by H(2)O(2) preconditioning against oxidative stress-induced apoptosis of PC12 cells has been demonstrated previously. In the present study, we investigated the effects of H(2)O(2) preconditioning on nuclear factor (NF)-kappaB activation and the role of NF-kappaB in the adaptive cytoprotection of H(2)O(2) preconditioning in PC12 cells. 2. The PC12 cells were preconditioned with 100 micromol/L H(2)O(2) for 90 min, followed by 24 h recovery and subsequent exposure to 300 micromol/L H(2)O(2) for a further 12 h. 3. The results showed that preconditioning with 100 micromol/L H(2)O(2) upregulated NF-kappaB expression and enhanced its nuclear translocation and DNA binding activity. In addition to its own effects on NF-kappaB expression, H(2)O(2) preconditioning also promoted the overexpression of NF-kappaB induced by a lethal concentration of H(2)O(2) (300 micromol/L). 4. N-Tosyl-l-phenylalanine chloromethyl ketone (TPCK; 20 micromol/L), an inhibitor of NF-kappaB, was administered 20 min before preconditioning with 100 micromol/L H(2)O(2). At this concenteration, TPCK blocked the overexpression of NF-kappaB induced by H(2)O(2) preconditioning, accompanied by attenuation of H(2)O(2) preconditioning-induced cytoprotection. The inhibition of NF-kappaB by TPCK enhanced caspase 3 activity induced by 300 micromol/L H(2)O(2). 5. The findings of the present study provide novel evidence for the effects of preconditioning with H(2)O(2) on constitutive activation of NF-kappaB, which contributes to the adaptive cytoprotection of H(2)O(2) preconditioning against PC12 cells apoptosis.
Zhang
Mei
M
Department of Physiology, Zhongshan Medical College, Sun Yat-sen University, Guangzhou, China.
Guo
Rui-Xian
RX
Mo
Li-Qiu
LQ
Liao
Xin-Xue
XX
Li
Wei
W
Zhi
Jun-Li
JL
Sun
Sheng-Nan
SN
Wang
Yan-Li
YL
Cui
Yu
Y
Liu
Wei
W
Feng
Jian-Qiang
JQ
Chen
Pei-Xi
PX
D021581:Active Transport, Cell Nucleus; D000310:Adrenal Gland Neoplasms / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D019610:Cytoprotection; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006861:Hydrogen Peroxide / Q000494:pharmacology* / Q000633:toxicity; D016877:Oxidants / Q000494:pharmacology* / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D010673:Pheochromocytoma / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D013997:Time Factors; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000378:metabolism*
D016877:Oxidants; C498145:Rela protein, rat; D051996:Transcription Factor RelA; D014108:Tosylphenylalanyl Chloromethyl Ketone; D004247:DNA; D006861:Hydrogen Peroxide