title: Nuclear factor-kappaB mediates cytoprotection of hydrogen peroxide preconditioning against apoptosis induced by oxidative stress in PC12 cells.
abstract: 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.
authors.affiliation: Department of Physiology, Zhongshan Medical College, Sun Yat-sen University, Guangzhou, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.forename: Rui-Xian
authors.initials: RX
authors.lastname: Guo
authors.forename: Li-Qiu
authors.initials: LQ
authors.lastname: Mo
authors.forename: Xin-Xue
authors.initials: XX
authors.lastname: Liao
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Jun-Li
authors.initials: JL
authors.lastname: Zhi
authors.forename: Sheng-Nan
authors.initials: SN
authors.lastname: Sun
authors.forename: Yan-Li
authors.initials: YL
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Cui
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Jian-Qiang
authors.initials: JQ
authors.lastname: Feng
authors.forename: Pei-Xi
authors.initials: PX
authors.lastname: Chen
mesh_terms: 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*
chemical_list: D016877:Oxidants; C498145:Rela protein, rat; D051996:Transcription Factor RelA; D014108:Tosylphenylalanyl Chloromethyl Ketone; D004247:DNA; D006861:Hydrogen Peroxide