Sirtuin 2 expression suppresses oxidative stress and senescence of nucleus pulposus cells through inhibition of the p53/p21 pathway

被引:47
作者
Yang, Maojie [1 ]
Peng, Yunyang [2 ]
Liu, Wei [1 ]
Zhou, Meng [1 ]
Meng, Qian [1 ]
Yuan, Chongming [3 ]
机构
[1] Tengzhou Cent Peoples Hosp, Dept Traumat Orthoped, Tengzhou, Peoples R China
[2] Tengzhou First Peoples Hosp, Dept Nursing, Tengzhou, Peoples R China
[3] Tengzhou Cent Peoples Hosp, Dept Spinal Surg, 181 Xingtan Rd, Tengzhou 277599, Peoples R China
关键词
Nucleus pulposus cells; Intervertebral disc degeneration; Sirtuin; 2; Oxidative stress; Cell senescence; CELLULAR SENESCENCE; REACTIVE OXYGEN; BACK; HEALTH; REGULATORS;
D O I
10.1016/j.bbrc.2019.03.200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Intervertebral disc degeneration (IDD) is a kind of disease associated with nucleus pulposus (NP) cell senescence. Previous studies have shown that the sirtuin family plays an extremely important role in the progress of cell aging. However, whether sirtuin2 (Sirt2) protects against IDD remains unknown. The aim of this study was to determine whether Sirt2 protected NP from degradation in IDD. The expression of Sirt2 in different degree of degenerate disc tissues was determined by reverse transcription-polymerase chain reaction. Interleukin 1 beta (IL-1 beta) was used to stimulate the degeneration of NP cells. Subsequently, lentivirus transfection was performed to increase Sirt2 expression in vitro. Meanwhile, the function of Sirt2 overexpression in the progress of NP cell degeneration was evaluated. Our study showed that the expression of Sirt2 markedly decreased in severe degenerated disc tissues. IL-1 beta significantly promoted the progress of IDD. Meanwhile, overexpression of Sirt2 could reverse the effects of IL-1 beta. The data also revealed that Sirt2 overexpression obviously increased the production of antioxidant SOD1/2 and suppressed oxidative stress in the disc. Moreover, p53 and p21 could be significantly suppressed by Sirt2 overexpression. These results suggested that Sirt2 prevented NP degradation via restraining oxidative stress and cell senescence through inhibition of the p53/p21 pathway. Furthermore, Sirt2 might become a novel target for IDD therapy in the future. (C) 2019 Published by Elsevier Inc.
引用
收藏
页码:616 / 622
页数:7
相关论文
共 35 条
[1]   Mechanical initiation of intervertebral disc degeneration [J].
Adams, MA ;
Freeman, BJC ;
Morrison, HP ;
Nelson, IW ;
Dolan, P .
SPINE, 2000, 25 (13) :1625-1636
[2]   Epidemiological features of chronic low-back pain [J].
Andersson, GBJ .
LANCET, 1999, 354 (9178) :581-585
[3]  
Casazza BA, 2012, AM FAM PHYSICIAN, V85, P343
[4]   The chemical biology of sirtuins [J].
Chen, Bing ;
Zang, Wenwen ;
Wang, Juan ;
Huang, Yajun ;
He, Yanhua ;
Yan, Lingling ;
Liu, Jiajia ;
Zheng, Weiping .
CHEMICAL SOCIETY REVIEWS, 2015, 44 (15) :5246-5264
[5]   Sirt6 overexpression suppresses senescence and apoptosis of nucleus pulposus cells by inducing autophagy in a model of intervertebral disc degeneration [J].
Chen, Jian ;
Xie, Jun-Jun ;
Jin, Meng-Yun ;
Gu, Yun-Tao ;
Wu, Cong-Cong ;
Guo, Wei-Jun ;
Yan, Ying-Zhao ;
Zhang, Zeng-Jie ;
Wang, Jian-Le ;
Zhang, Xiao-Lei ;
Lin, Yan ;
Sun, Jia-Li ;
Zhu, Guang-Hui ;
Wang, Xiang-Yang ;
Wu, Yao-Sen .
CELL DEATH & DISEASE, 2018, 9
[6]   ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age-Related Diseases [J].
Davalli, Pierpaola ;
Mitic, Tijana ;
Caporali, Andrea ;
Lauriola, Angela ;
D'Arca, Domenico .
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, 2016, 2016
[7]  
FENG C, 2017, OXID MED CELL LONGEV, V2017, DOI DOI 10.1155/2017/5601593
[8]   Muscle energy technique for non-specific low-back pain [J].
Franke, Helge ;
Fryer, Gary ;
Ostelo, Raymond W. J. G. ;
Kamper, Steven J. .
COCHRANE DATABASE OF SYSTEMATIC REVIEWS, 2015, (02)
[9]   Oxidative stress activates a specific p53 transcriptional response that regulates cellular senescence and aging [J].
Gambino, Valentina ;
De Michele, Giulia ;
Venezia, Oriella ;
Migliaccio, Pierluigi ;
Dall'Olio, Valentina ;
Bernard, Loris ;
Minardi, Simone Paolo ;
Della Fazia, Maria Agnese ;
Bartoli, Daniela ;
Servillo, Giuseppe ;
Alcalay, Myriam ;
Luzi, Lucilla ;
Giorgio, Marco ;
Scrable, Heidi ;
Pelicci, Pier Giuseppe ;
Migliaccio, Enrica .
AGING CELL, 2013, 12 (03) :435-445
[10]   Emerging Role of Sirtuin 2 in the Regulation of Mammalian Metabolism [J].
Gomes, Pedro ;
Outeiro, Tiago Fleming ;
Cavadas, Claudia .
TRENDS IN PHARMACOLOGICAL SCIENCES, 2015, 36 (11) :756-768