TIGAR mediates the inhibitory role of hypoxia on ROS production and apoptosis in rat nucleus pulposus cells

被引：56

作者：

Jiang, L-B. ^{[1
]}

Cao, L. ^{[1
]}

Ma, Y-Q. ^{[1
]}

Chen, Q. ^{[1
]}

Liang, Y. ^{[1
]}

Yuan, F-L. ^{[1
]}

Li, X-L. ^{[1
]}

Dong, J. ^{[1
]}

Chen, N. ^{[2
]}

机构：

[1] Fudan Univ, Zhongshan Hosp, Dept Orthoped Surg, 180 Fenglin Rd, Shanghai 200032, Peoples R China

[2] Fudan Univ, Zhongshan Hosp, Dept Orthoped Surg, Qingpu Branch, Shanghai, Peoples R China

来源：

OSTEOARTHRITIS AND CARTILAGE | 2018年 / 26卷 / 01期

基金：

国家高技术研究发展计划(863计划);

关键词：

Intervertebral disc degeneration; Nucleus pulposus; Hypoxia; Reactive oxygen species; TP53-induced glycolysis and apoptosis regulator; PEROXIDE-INDUCED APOPTOSIS; OXIDATIVE STRESS; DISC DEGENERATION; GLYCOLYSIS; INJURY; PROLIFERATION; INFLAMMATION; HIF-1-ALPHA; ACTIVATION; EXPRESSION;

D O I：

10.1016/j.joca.2017.10.007

中图分类号：

R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学（修复外科学）];

学科分类号：

摘要：

Objective: Hypoxia has been shown to inhibit reactive oxygen species (ROS) production in nucleus pulposus (NP) cells. The TP53-induced glycolysis and apoptosis regulator (TIGAR) has been reported to suppress oxidative stress. We sought to explore the role of TIGAR in the effect of hypoxia on ROS production and apoptosis. Methods: An intervertebral disc degeneration (IDD) model of Sprague-Dawley (SD) rat caudal spine was established by puncturing the Co6-7 disc. TIGAR expression was detected by immunohistochemistry and western blotting in human and SD rat NP tissues of degenerated discs. Rat primary NP cells treated with hypoxia and cobalt chloride (CoCl2) were analyzed by western blotting for TIGAR expression. After TIGAR silence with TIGAR siRNA transfection, apoptosis percentage, mitochondrial and total intracellular ROS levels were measured. H2O2 was used to further check the effects of TIGAR on oxidative stress. Finally, NADPH/NADP(+) and GSH/GSSH ratio were examined after TIGAR silencing under hypoxic conditions and after H2O2 treatment. Results: A degree-dependent increase in TIGAR expression was observed in human and rat degenerated NP tissues. Hypoxia and hypoxia-inducer CoCl2 enhanced TIGAR and P53 expressions in rat NP cells. TIGAR silence reversed the inhibitory effects of hypoxia on intracellular and mitochondrial ROS production, as well as apoptosis percentage. However, TIGAR silence aggravated H2O2-induced ROS production. In addition, TIGAR increased NADPH/NADP(+) and GSH/GSSH ratio in NP cells. Conclusions: These results suggested that TIGAR appears to mediate the protective role of hypoxia on ROS production and apoptosis percentage by enhancing NADPH/NADP(+) and GSH/GSSH ratio. (c) 2017 Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.

引用

页码：138 / 148

页数：11

共 34 条

[1]

Ardyanto TD, 2006, INT J ONCOL, V29, P549

[2] TIGAR, a p53-inducible regulator of glycolysis and apoptosis [J].

Bensaad, Karim ;

Tsuruta, Atsushi ;

Selak, Mary A. ;

Calvo Vidal, M. Nieves ;

Nakano, Katsunori ;

Bartrons, Ramon ;

Gottlieb, Eyal ;

Vousden, Karen H. .

CELL, 2006, 126 (01) :107-120

[3] The relationship between height, shape and histological changes in early degeneration of the lower lumbar discs [J].

Berlemann U. ;

Gries N.C. ;

Moore R.J. .

European Spine Journal, 1998, 7 (3) :212-217

[4] Protective effect of cannabidiol on hydrogen peroxide-induced apoptosis, inflammation and oxidative stress in nucleus pulposus cells [J].

Chen, Jie ;

Hou, Chen ;

Chen, Xin ;

Wang, Dong ;

Yang, Pinglin ;

He, Xijing ;

Zhou, Jinsong ;

Li, Haopeng .

MOLECULAR MEDICINE REPORTS, 2016, 14 (03) :2321-2327

[5] m-Polar Fuzzy Sets: An Extension of Bipolar Fuzzy Sets [J].

Chen, Juanjuan ;

Li, Shenggang ;

Ma, Shengquan ;

Wang, Xueping .

SCIENTIFIC WORLD JOURNAL, 2014,

[6] Mitochondrial localization of TIGAR under hypoxia stimulates HK2 and lowers ROS and cell death [J].

Cheung, Eric C. ;

Ludwig, Robert L. ;

Vousden, Karen H. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (50) :20491-20496

[7] Plumbagin exerts protective effects in nucleus pulposus cells by attenuating hydrogen peroxide-induced oxidative stress, inflammation and apoptosis through NF-B and Nrf-2 [J].

Chu, Hui ;

Yu, Hang ;

Ren, Ding ;

Zhu, Kejun ;

Huang, Hong .

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 2016, 37 (06) :1669-1676

[8] OXIDATIVE STRESS INHIBITS THE PROLIFERATION, INDUCES PREMATURE SENESCENCE AND PROMOTES A CATABOLIC PHENOTYPE IN HUMAN NUCLEUS PULPOSUS INTERVERTEBRAL DISC CELLS [J].

Dimozi, A. ;

Mavrogonatou, E. ;

Sklirou, A. ;

Kletsas, D. .

EUROPEAN CELLS & MATERIALS, 2015, 30 :89-103

[9]

Experimentation H., 1964, Can Med Assoc J, V91, P619

[10] Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing [J].

Guzy, RD ;

Hoyos, B ;

Robin, E ;

Chen, H ;

Liu, LP ;

Mansfield, KD ;

Simon, MC ;

Hammerling, U ;

Schumacker, PT .

CELL METABOLISM, 2005, 1 (06) :401-408

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