Autophagy is activated in compression-induced cell degeneration and is mediated by reactive oxygen species in nucleus pulposus cells exposed to compression
Autophagy is activated in compression-induced cell degeneration and is mediated by reactive oxygen species in nucleus pulposus cells exposed to compression
复制标题
自噬在压迫引起的细胞变性中被激活，并由暴露于压迫的髓核细胞中的活性氧介导
DOI：
10.1016/j.joca.2013.10.002
复制
发表时间：
2013-12-01
影响因子：
7
通讯作者：
Chen, S. -F.
中科院分区：
文献类型：
--
作者：
Ma, K. -G.;Shao, Z. -W.;Chen, S. -F.
目的：目的探讨自噬是否参与椎间盘退变性疾病（DDD）的发病机制或延缓椎间盘退变，并探讨压力诱导的自噬与髓核细胞内活性氧（ROS）的关系。方法：应用自噬体及自噬相关标志物，通过电镜直接检测，探讨压力作用下大鼠髓核细胞自噬的作用，单丹酰尸胺（MDC）染色、免疫荧光、蛋白质印迹，并间接通过分析自噬的药理学抑制剂如3-甲基腺嘌呤（3-MA）和氯喹（CQ）的影响。Annexin-W-propidium iodide（PI）-fluorescein染色观察自噬与凋亡的关系。此外，ROS进行测量，以确定这些因素是否是负责的发展压缩诱导的autophagy.Results：我们的研究结果表明，大鼠NP细胞激活自噬响应相同的强凋亡刺激，引发细胞凋亡的压缩。自噬和凋亡是相互联系和协调的大鼠NP细胞暴露于压力刺激。结论：自噬对NP细胞损伤成分的降解增强可能是NP细胞对抗机械过载的一种重要生存反应，广泛的自噬可能触发细胞自噬性死亡。调节自噬和减少细胞内ROS的产生可以延缓IVD的变性。(C)2013年国际骨关节炎研究学会。由爱思唯尔有限公司出版。保留所有权利。
Objective: To determine whether autophagy contributes to the pathogenesis of degenerative disc disease (DDD) or retards the intervertebral disc (IVD) degeneration, and investigate the possible relationship between compression-induced autophagy and intracellular reactive oxygen species (ROS) in nucleus pulposus (NP) cells in vitro.Methods: The autophagosome and autophagy-related markers were used to explore the role of autophagy in rat NP cells under compressive stress, which were measured directly by electronic microscopy, monodansylcadaverine (MDC) staining, immunofluorescence, western blot, and indirectly by analyzing the impact of pharmacological inhibitors of autophagy such as 3-methyladenine (3-MA) and chloroquine (CQ). And the relationship between autophagy and apoptosis was investigated by Annexin-Wpropidium iodide (PI)-fluorescein staining. In addition, ROS were measured to determine whether these factors are responsible for the development of compression-induced autophagy.Results: Our results indicated that rat NP cells activated autophagy in response to the same strong apoptotic stimuli that triggered apoptosis by compression. Autophagy and apoptosis were interconnected and coordinated in rat NP cells exposed to compression stimuli. Compression-induced autophagy was closely related to intracellular ROS production.Conclusions: Enhanced degradation of damaged components of NP cells by autophagy may be a crucial survival response against mechanical overload, and extensive autophagy may trigger autophagic cell death. Regulating autophagy and reducing the generation of intracellular ROS may retard IVD degeneration. (C) 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.