Bu Xiaosong, Wu De, Lu Xiaomei, Yang Li, Xu Xiaoyan, Wang Juan, Tang Jiulai
Department of Pediatrics, The First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China.
Neuropsychiatr Dis Treat. 2017 Jun 23;13:1633-1645. doi: 10.2147/NDT.S129081. eCollection 2017.
Autistic spectrum disorder (ASD) is a neurodevelopmental disorder and has a high prevalence in children. Recently, mitochondrial oxidative stress has been proposed to be associated with ASD. Besides, SIRT1/PGC-1α signaling plays an important role in combating oxidative stress. In this study, we sought to determine the role of SIRT1/PGC-1α signaling in the ASD lymphoblastoid cell lines (LCLs). In this study, the mRNA and protein expressions of SIRT1/PGC-1α axis genes were assessed in 35 children with ASD and 35 healthy controls (matched for age, gender, and IQ). An immortalized LCL was established by transforming lymphocytes with Epstein-Barr virus. Next, we used ASD LCLs and control LCLs to detect SIRT1/PGC-1α axis genes expression and oxidative damage. Finally, the effect of overexpression of PGC-1α on oxidative injury in the ASD LCLs was determined. SIRT1/PGC-1α axis genes expression was downregulated at RNA and protein levels in ASD patients and LCLs. Besides, the translocation of cytochrome and DIABLO from mitochondria to the cytosol was found in the ASD LCLs. Moreover, the intracellular reactive oxygen species (ROS) and mitochondrial ROS and cell apoptosis were increased in the ASD LCLs. However, overexpression of PGC-1α upregulated the SIRT1/PGC-1α axis genes expression and reduced cytochrome and DIABLO release in the ASD LCLs. Also, overexpression of PGC-1α reduced the ROS generation and cell apoptosis in the ASD LCLs. Overexpression of PGC-1α could reduce the oxidative injury in the ASD LCLs, and PGC-1α may act as a target for treatment.
自闭症谱系障碍（ASD）是一种神经发育障碍，在儿童中具有较高的患病率。最近，线粒体氧化应激被认为与ASD有关。此外，SIRT1/PGC-1α信号通路在对抗氧化应激中起重要作用。在本研究中，我们试图确定SIRT1/PGC-1α信号通路在ASD淋巴母细胞系（LCLs）中的作用。在本研究中，评估了35例ASD儿童和35例健康对照（年龄、性别和智商匹配）中SIRT1/PGC-1α轴基因的mRNA和蛋白表达。通过用爱泼斯坦-巴尔病毒转化淋巴细胞建立了永生化LCL。接下来，我们使用ASD LCLs和对照LCLs检测SIRT1/PGC-1α轴基因表达和氧化损伤。最后，确定了PGC-1α过表达对ASD LCLs氧化损伤的影响。ASD患者和LCLs中SIRT1/PGC-1α轴基因的表达在RNA和蛋白水平均下调。此外，在ASD LCLs中发现细胞色素和DIABLO从线粒体转移到细胞质中。此外，ASD LCLs中细胞内活性氧（ROS）、线粒体ROS和细胞凋亡增加。然而，PGC-1α过表达上调了ASD LCLs中SIRT1/PGC-1α轴基因的表达，并减少了细胞色素和DIABLO的释放。此外，PGC-1α过表达减少了ASD LCLs中ROS的产生和细胞凋亡。PGC-1α过表达可以减轻ASD LCLs中的氧化损伤，PGC-1α可能成为治疗靶点。
