title: Tetramethylpyrazine protects lymphocytes from radiation-induced apoptosis through nuclear factor-κB.
abstract: OBJECTIVE
  Radiation induces an important apoptosis response in irradiated organs. The objective of this study was to investigate the radioprotective effect of tetramethylpyrazine (TMP) on irradiated lymphocytes and discover the possible mechanism of protection.
  
  
  METHODS
  Lymphocytes were pretreated for 12 h with TMP (25-200 μmol·L(-1)) and then exposed to 4 Gy radiation. Cell apoptosis and the signaling pathway were analyzed.
  
  
  RESULTS
  Irradiation increased cell death, DNA fragmentation, activated caspase activation and cytochrome c translocation, downregulated B-cell lymphoma 2 (Bcl-2) and up-regulated Bcl-2-associated X protein (Bax). Pretreated with TMP significantly reversed this tendency. Several anti-apoptotic characteristics of TMP, including the ability to increase cell viability, inhibit caspase-9 activation, and upregulate Bcl-2 and down-regulate Bax in 4Gy-irradiated lymphocytes were determined. Signal pathway analysis showed TMP could translate nuclear factor-κB (NF-κB) from cytosol into the nucleus.
  
  
  CONCLUSIONS
  The results suggest that TMP had a radioprotective effect through the NF-κB pathway to inhibit apoptosis, and it may be an effective candidate for treating radiation diseases associated with cell apoptosis.
authors.affiliation: Institute of Radiation Medicine, Academy of Military Medical Science, Beijing 100850, China; Chongqing Maternal and Child Health-Care Hospital, Chongqing 400016, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Institute of Radiation Medicine, Academy of Military Medical Science, Beijing 100850, China. Electronic address: 13681121635@139.com.
authors.forename: Zeng-Chun
authors.initials: ZC
authors.lastname: Ma
authors.affiliation: Institute of Radiation Medicine, Academy of Military Medical Science, Beijing 100850, China.
authors.forename: Yu-Guang
authors.initials: YG
authors.lastname: Wang
authors.affiliation: Institute of Radiation Medicine, Academy of Military Medical Science, Beijing 100850, China.
authors.forename: Hong-Ling
authors.initials: HL
authors.lastname: Tan
authors.affiliation: Institute of Radiation Medicine, Academy of Military Medical Science, Beijing 100850, China.
authors.forename: Cheng-Rong
authors.initials: CR
authors.lastname: Xiao
authors.affiliation: Institute of Radiation Medicine, Academy of Military Medical Science, Beijing 100850, China.
authors.forename: Qian-De
authors.initials: QD
authors.lastname: Liang
authors.affiliation: Institute of Radiation Medicine, Academy of Military Medical Science, Beijing 100850, China.
authors.forename: Xiang-Lin
authors.initials: XL
authors.lastname: Tang
authors.affiliation: Chongqing Maternal and Child Health-Care Hospital, Chongqing 400016, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Institute of Radiation Medicine, Academy of Military Medical Science, Beijing 100850, China. Electronic address: gaoyue@bmi.ac.cn.
authors.forename: Yue
authors.initials: Y
authors.lastname: Gao
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D053938:DNA Fragmentation / Q000187:drug effects / Q000528:radiation effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D011719:Pyrazines / Q000494:pharmacology*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D011719:Pyrazines; D011837:Radiation-Protective Agents; D051028:bcl-2-Associated X Protein; C017953:tetramethylpyrazine
keywords: Apoptosis; NF-κB; Radioprotection; Tetramethylpyrazine