title: [Role of nuclear factor-κB activation in bilirubin-induced rat hippocampal neuronal apoptosis and the effect of TAT-NBD intervention].
abstract: OBJECTIVE
  To investigate the role of nuclear factor-κB (NF-κB) activation in bilirubin-induced apoptosis of rat hippocampal neurons and the effect of TAT-NBD intervention on bilirubin neurotoxicity.
  
  
  METHODS
  Primary-cultured rat hippocampal neurons were treated with TAT-NBD in the initial 6 or 24 h or in the latter 6 h during a 24-h bilirubin exposure of the cells (early, continuous and late intervention groups, respectively). Immunocytochemistry was performed to detect NF-κB p65 protein expression, and the cell survival and apoptosis were assessed with a modified MTT assay, Annexin V-FITC/PI and TUNEL assay. IL-1β concentration in the supernatant was determined with ELISA.
  
  
  RESULTS
  Compared with the control cells, bilirubin-treated cells showed a significantly increased NF-κB p65 protein expression (P<0.01), which reached the peak level at 6 and 24 h (P<0.01). The cell survival rate in early TAT-NBD intervention group was (80.784∓9.767)%, significantly lower than that of the control group (P<0.01) but higher than that of bilirubin group (P<0.01); the apoptotic rate in early TAT-NBD intervention group was significantly higher than that of control group (P<0.01) but lower than that of bilirubin group (P<0.01). IL-1β concentration was significantly lower in early TAT-NBD intervention group (15.348∓0.812 pg/ml) than in bilirubin group (P<0.05). The continuous and late TAT-NBD intervention groups showed comparable cell survival rate, apoptotic rate and IL-1β concentration with bilirubin group (P>0.05).
  
  
  CONCLUSIONS
  NF-κB bidirectionally regulates bilirubin-induced apoptosis of rat hippocampal neurons. Selective inhibition of the early peak of NF-κB by TAT-NBD offers neuroprotective effect. TAT-NBD can be potentially used for prophylaxis of bilirubin-induced brain injury.
authors: Department of Neonatology, Chongqing Medical University, Chongqing, China. songsijie7@163.com
authors: Sijie
authors: S
authors: Song
authors: Yefang
authors: Y
authors: Zhu
authors: Shanshan
authors: S
authors: Dang
authors: Shaowen
authors: S
authors: Wang
authors: Ziyu
authors: Z
authors: Hua
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001663:Bilirubin / Q000633:toxicity*; D002470:Cell Survival; D002478:Cells, Cultured; D005260:Female; D006624:Hippocampus / Q000166:cytology; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D051996:Transcription Factor RelA / Q000378:metabolism*
chemical_list: D053583:Interleukin-1beta; D018696:Neuroprotective Agents; D010455:Peptides; C498145:Rela protein, rat; D051996:Transcription Factor RelA; D001663:Bilirubin