Research Paper Volume 12, Issue 8 pp 7534—7548
Protective effects of autophagy and NFE2L2 on reactive oxygen species-induced pyroptosis of human nucleus pulposus cells
- 1 Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Yuzhong 400016, Chongqing, China
- 2 Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Yuzhong 400016, Chongqing, China
Received: January 14, 2020 Accepted: March 4, 2020 Published: April 22, 2020
https://doi.org/10.18632/aging.103109How to Cite
Copyright © 2020 Bai et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
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.
Abbreviations
IDD: intervertebral disc degeneration; NPCs: nucleus Pulposus Cells; ROS: reactive oxygen species; MRI: magnetic resonance imaging; LDH: lumbar disc herniation; PTED: percutaneous transforaminal endoscopic discectomy; DAMPs: danger-associated molecular patterns (s); PAMPs: pathogen-associated molecular patterns (s); LPS: lipopolysaccharide; SOD: superoxide dismutase; PBS: phosphate buffered saline; NAC: N-Acetyl-L-cysteine; DCF: dichlorofluorescein; TBST: tris-buffered saline and tween 20; MOI: multiplicity of infection.