Luo Hao, Liang Hairong, Chen Jiajia, Xu Yongchun, Chen Yuting, Xu Longmei, Yun Lin, Liu Jiaxian, Yang Hui, Liu Linhua, Peng Jianming, Liu Zhidong, Tang Lin, Chen Wen, Tang Huanwen
Department of Environmental and Occupational Health, Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, China.
Huizhou Prevention and Treatment Centre for Occupational Disease, Huizhou, China.
Environ Toxicol. 2017 Sep;32(9):2163-2171. doi: 10.1002/tox.22429. Epub 2017 Apr 26.
Hydroquinone (HQ), one of the most important metabolites derived from benzene, induces cell cycle arrest and apoptosis. Poly(ADP-ribose) polymerase-1 (PARP-1) participates in various biological processes, including DNA repair and cell cycle regulation. To explore whether PARP-1 regulatory pathway mediated HQ-induced cell cycle arrest and apoptosis, we assessed the effect of PARP-1 suppression on induction of apoptosis analyzed by FACSCalibur flow cytometer in PARP-1 deficientTK6 cells (TK6-shPARP-1). We observed an increase in the fraction of cells in G1 phase by 7.6% and increased apoptosis by 4.5% in PARP-1-deficient TK6 cells (TK6-shPARP-1) compared to those negative control cells (TK6-shNC cells) in response to HQ treatment. Furthermore, HQ might activate the extrinsic pathways of apoptosis via up-regulation of Fas expression, followed by caspase-3 activation, apoptotic body, and sub G1 accumulation. Enhanced p53 expression was observed in TK6-shPARP-1 cells than in TK6-shNC cells after HQ treatment. In contrast, Fas expression was lower in TK6-shPARP-1 cells than in TK6-shNC cells. Therefore, we conclude that HQ may activate apoptotic signals via Fas up-regulation and p53-mediated apoptosis in TK6-shNC cells. The reduction of PARP-1 expression further intensified up-regulation of p53 in TK6-shPARP-1 cells, resulting in an increased G1→S phase cell arrest and apoptosis in TK6-shPARP-1 cells compared to TK6-shNC cells.
对苯二酚（HQ）是苯衍生的最重要代谢产物之一，可诱导细胞周期停滞和凋亡。聚（ADP-核糖）聚合酶-1（PARP-1）参与包括DNA修复和细胞周期调控在内的各种生物学过程。为了探究PARP-1调节途径是否介导了HQ诱导的细胞周期停滞和凋亡，我们评估了PARP-1抑制对PARP-1缺陷型TK6细胞（TK6-shPARP-1）中通过FACSCalibur流式细胞仪分析的凋亡诱导的影响。我们观察到，与阴性对照细胞（TK6-shNC细胞）相比，在HQ处理下，PARP-1缺陷型TK6细胞（TK6-shPARP-1）中G1期细胞比例增加了7.6%，凋亡增加了4.5%。此外，HQ可能通过上调Fas表达激活凋亡的外源性途径，随后激活caspase-3、形成凋亡小体并导致亚G1期积累。HQ处理后，TK6-shPARP-1细胞中p53表达比TK6-shNC细胞增强。相反，TK6-shPARP-1细胞中Fas表达低于TK6-shNC细胞。因此，我们得出结论，HQ可能通过上调Fas和p53介导的凋亡在TK6-shNC细胞中激活凋亡信号。PARP-1表达的降低进一步加剧了TK6-shPARP-1细胞中p53的上调，导致与TK6-shNC细胞相比，TK6-shPARP-1细胞中G1→S期细胞停滞和凋亡增加。
