title: Therapeutic potential of BAK gene silencing in aluminum induced neural cell degeneration.
abstract: Previous studies have demonstrated robust BAK gene silencing via RNA interference (RNAi). To investigate whether BAK RNAi may serve as a co-therapeutic agent in neural cell death, we herein established a cell degeneration model using a human neuroblastoma cell line (SH-SY5Y) treated by aluminum (Al). Combining cell viability assays and expression analyses by QRT (quantitative real-time)-PCR and immunocytochemistry, we selected and validated the optimal small interfering RNA (siRNA) from three candidate siRNAs for the BAK gene. Our data identified siRNA1 as the most effective siRNA; the optimal concentration of the transfection agent was 10nM and the optimal incubation period was 24h. The transfection and knockdown efficiency was 93% and 58%, respectively, which closely correlated with the BAK protein expression. SH-SY5Y cells with BAK knockdown showed a clear resistance against cell death and Al-induced apoptosis. These results indicate that genetic inactivation of BAK could be an effective strategy in delaying the onset of apoptosis in Al-treated cells, and exemplify the therapeutic potential of RNAi-based methods for the treatment of neural cell degeneration.
authors.affiliation: Shanxi Medical University, Taiyuan, Shanxi 030001, China.
authors.forename: Q L
authors.initials: QL
authors.lastname: Zhang
authors.forename: Q
authors.initials: Q
authors.lastname: Niu
authors.forename: Y T
authors.initials: YT
authors.lastname: Shi
authors.forename: P Y
authors.initials: PY
authors.lastname: Niu
authors.forename: C Y
authors.initials: CY
authors.lastname: Liu
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: C
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000535:Aluminum / Q000633:toxicity*; D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival; D006801:Humans; D046529:Microscopy, Electron, Transmission; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology / Q000628:therapy*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics*
chemical_list: D034741:RNA, Small Interfering; D050998:bcl-2 Homologous Antagonist-Killer Protein; D000535:Aluminum