PDF(Pubmed)
Abstract：
The fragment of satellite III (f-SatIII) is located in pericentromeric heterochromatin of chromosome 1. Cell with an enlarged f-SatIII block does not respond to various stimuli and are highly stress-susceptible. The fraction of f-SatIII in the cells of schizophrenia patients changed during antipsychotic therapy. Therefore, antipsychotics might reduce the f-SatIII content in the cells. We studied the action of haloperidol, risperidone and olanzapine (3 h, 24 h, 96 h) on human skin fibroblast lines (n = 10). The f-SatIII contents in DNA were measured using nonradioactive quantitative hybridization. RNASATIII were quantified using RT-qPCR. The levels of DNA damage markers (8-oxodG, γ-H2AX) and proteins that regulate apoptosis and autophagy were determined by flow cytometry. The antipsychotics reduced the f-SatIII content in DNA and RNASATIII content in RNA from HSFs. After an exposure to the antipsychotics, the autophagy marker LC3 significantly increased, while the apoptosis markers decreased. The f-SatIII content in DNA positively correlated with RNASATIII content in RNA and with DNA oxidation marker 8-oxodG, while negatively correlated with LC3 content. The antipsychotics arrest the process of f-SatIII repeat augmentation in cultured skin fibroblasts via the transcription suppression and/or through upregulated elimination of cells with enlarged f-SatIII blocks with the help of autophagy.
摘要：
卫星III（f-SatIII）的片段位于1号染色体的着丝粒周异染色质中。具有扩大的f-SatIII阻滞的细胞对各种刺激没有反应并且是高度应激易感的。在抗精神病治疗期间，精神分裂症患者细胞中f-SatIII的比例发生了变化。因此,抗精神病药物可能会降低细胞中f-SatIII的含量。我们研究了氟哌啶醇的作用,利培酮和奥氮平（3小时，24h,96h）对人皮肤成纤维细胞系（n=10）。使用非放射性定量杂交测量DNA中的f-SatIII含量。使用RT-qPCR定量RNASATIII。DNA损伤标记物的水平（8-oxodG，γ-H2AX）和调节凋亡和自噬的蛋白质通过流式细胞术测定。抗精神病药降低了来自HSF的DNA中的f-SatIII含量和RNA中的RNASATIII含量。在接触抗精神病药物后，自噬标记LC3显著增加，而凋亡标志物下降。DNA中的f-SatIII含量与RNA中的RNASATIII含量以及DNA氧化标记8-oxodG呈正相关，而与LC3含量呈负相关。抗精神病药通过转录抑制和/或通过在自噬的帮助下具有扩大的f-SatIII阻断的细胞的上调消除来阻止培养的皮肤成纤维细胞中f-SatIII重复增加的过程。
