Protective effects of autophagy and NFE2L2 on reactive oxygen species-induced pyroptosis of human nucleus pulposus cells
Protective effects of autophagy and NFE2L2 on reactive oxygen species-induced pyroptosis of human nucleus pulposus cells
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DOI：
10.18632/aging.103109
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发表时间：
2020-04-30
期刊：
影响因子：
5.2
通讯作者：
Hu, Zhenming
中科院分区：
文献类型：
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作者：
Bai, Zhibiao;Liu, Wei;Hu, Zhenming
椎间盘退变（IDD）的特征是髓核细胞（NPC）减少。随着退变程度的加重，髓核组织中活性氧（ROS）增加。焦亡是一种新发现的细胞死亡形式，其与NPC中氧化应激的关系尚不清楚。本研究旨在探讨氧化应激条件下NPC的热凋亡机制。通过手术治疗从IDD患者中分离NPC。Western blot检测细胞内NLR家族pyrin domain containing 3（NLRP 3）和PYD and CARD domain containing（PYCARD）蛋白的表达，Hochest 33342/PI双染或扫描电镜观察细胞膜孔的形成。结果表明，ROS诱导NPC的细胞凋亡依赖于NLRP 3和PYCARD的表达。增加的ROS水平还增加转录因子核因子红细胞2样2（NFE 2L 2，Nrf 2）和NPC的自噬，这两者都减弱了焦亡。总之，ROS通过NLRP 3/ PYCARD途径诱导NPC的焦亡，并通过增加自噬和NFE 2L 2建立负调控。这些发现为进一步了解IDD的发病机制和治疗IDD提供了新的思路。
Intervertebral disc degeneration (IDD) is characterized by the decrease of nucleus pulposus cells (NPCs). With the increase of the degree of degeneration, the reactive oxygen species (ROS) in nucleus pulposus tissue increases. Pyroptosis is a newly discovered form of cell death and its relationship with oxidative stress in NPCs remains unclear. This study was performed to investigate the mechanisms of pyroptosis of NPCs under oxidative stress. NPCs were isolated from IDD patients by surgical treatment. Pyroptosis related proteins like NLR family pyrin domain containing 3(NLRP3) and PYD and CARD domain containing (PYCARD) were detected by western blot, and membrane pore formation was observed by hochest33342/PI double staining or scanning electron microscope. The results showed that ROS induced the pyroptosis of NPCs and it depended on the expression of NLRP3 and PYCARD. The increased ROS level also increased transcription factor nuclear factor, erythroid 2 like 2 (NFE2L2, Nrf2) and the autophagy of NPCs, both of which attenuated the pyroptosis. In summary, ROS induces the pyroptosis of NPCs through the NLRP3/ PYCARD pathway, and establishes negative regulation by increasing autophagy and NFE2L2. These findings may provide a better understanding of the mechanism of IDD and potential therapeutic approaches for IDD treatment.