title: [Study on mechanism of trimethyltin chloride-induced apoptosis in PC12 cells].
abstract: OBJECTIVE
  To investigate the effects of trimethyltin chloride (TMT) on proliferation, apoptosis, oxidative damage, and NF-κB expression in PC12 cells in vitro.
  
  
  METHODS
  PC12 cells were treated with 0, 0.3125, 0.6250, 1.2500, 2.5000, 5.0000, 10.0000, and 20.0000 µmol/L TMT for 24 and 48 h, and MTT assay was used to evaluate cell viability. PC12 cells were treated with 1.25, 2.50, 5.00, and 10.00 µmol/L TMT for 12 and 24 h, and flow cytometry was used to measure the apoptotic rates of cells. PC12 cells were treated with 1.25, 2.50, 5.00, and 10.00 µmol/L TMT for 6 h, and the reactive oxygen species (ROS) and glutathione (GSH) levels were measured. PC12 cells were treated with 1.25, 2.50, 5.00, and 10.00 µmol/L TMT for 12 h, and Western blot was used to measure NF-κB levels.
  
  
  RESULTS
  Compared with solvent controls, the PC12 cells treated with 2.5000, 5.0000, 10.0000, and 20.0000 µmol/L TMT for 24 h showed significantly decreased cell viability (P < 0.05); the PC12 cells treated with 1.2500, 2.5000, 5.0000, 10.0000, and 20.0000 µmol/L TMT for 48 h showed significantly decreased cell viability (P < 0.05). The PC12 cells treated with 1.2500, 2.5000, 5.0000, and 10.0000 µmol/L TMT for 12 h had apoptotic rates of 15.30% ± 0.75%, 18.90% ± 0.61%, 22.00% ± 0.60%, and 36.50% ± 0.66%, respectively, and the PC12 cells treated with 1.25, 2.50, 5.00, and 10.00 µmol/L TMT for 24 h had apoptotic rates of 28.6% ± 0.40%, 43.54% ± 2.00%, 65.73% ± 0.71%, and 74.67% ± 0.40%, respectively, all significantly higher than those of the control group (12 h: 12.80% ± 1.00%, 24h: 16.83% ± 0.25%) (P < 0.05). The ROS fluorescence intensities of the PC12 cells treated with 1.25, 2.50, 5.00, and 10.00 µmol/L TMT were 1.42, 1.71, 1.78, and 1.89 times that of the control group (P < 0.05); the PC12 cells treated with 2.50, 5.00, and 10.00 µmol/L TMT had GSH levels of 0.17 ± 0.0, 0.20 ± 0.04, and 0.07 ± 0.03 µmol/µg protein, significantly lower than that of the control group (0.30 ± 0.01 µmol/L protein) (P < 0.05). The PC12 cells treated with 2.50, 5.00, and 10.00 µmol/L TMT had significantly higher expression of NF-κB p65 than the control group (P < 0.05).
  
  
  CONCLUSIONS
  Under our laboratory conditions, TMT can significantly inhibit proliferation and induce apoptosis in PC12 cells, which may be related to oxidative stress and NF-κB signaling pathway activation.
authors.affiliation: Department of Health Toxicology, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Yan-fang
authors.initials: YF
authors.lastname: Liang
authors.forename: Yan
authors.initials: Y
authors.lastname: Qing
authors.forename: Qing-qing
authors.initials: QQ
authors.lastname: DU
authors.forename: Pan
authors.initials: P
authors.lastname: Fan
authors.forename: Yi-ping
authors.initials: YP
authors.lastname: Xu
authors.forename: Han-gong
authors.initials: HG
authors.lastname: Xu
authors.forename: Nian
authors.initials: N
authors.lastname: Shi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D051381:Rats; D051996:Transcription Factor RelA / Q000378:metabolism; D014298:Trimethyltin Compounds / Q000633:toxicity*
chemical_list: C498145:Rela protein, rat; D051996:Transcription Factor RelA; D014298:Trimethyltin Compounds; C040533:trimethyltin chloride