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TIGAR mediates the inhibitory role of hypoxia on ROS production and apoptosis in rat nucleus pulposus cells.
Osteoarthritis Cartilage. 2018 01; 26(1):138-148.OC

Abstract

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.

Authors+Show Affiliations

Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: li.xilei@zs-hospital.sh.cn.Department of Orthopedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: dong.jian@zs-hospital.sh.cn.Department of Orthopedic Surgery, Zhongshan Hospital, Qingpu Branch, Fudan University, Shanghai, China. Electronic address: chen.nong@qphospital.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29061494

Citation

Jiang, L-B, et al. "TIGAR Mediates the Inhibitory Role of Hypoxia On ROS Production and Apoptosis in Rat Nucleus Pulposus Cells." Osteoarthritis and Cartilage, vol. 26, no. 1, 2018, pp. 138-148.
Jiang LB, Cao L, Ma YQ, et al. TIGAR mediates the inhibitory role of hypoxia on ROS production and apoptosis in rat nucleus pulposus cells. Osteoarthr Cartil. 2018;26(1):138-148.
Jiang, L. B., Cao, L., Ma, Y. Q., Chen, Q., Liang, Y., Yuan, F. L., Li, X. L., Dong, J., & Chen, N. (2018). TIGAR mediates the inhibitory role of hypoxia on ROS production and apoptosis in rat nucleus pulposus cells. Osteoarthritis and Cartilage, 26(1), 138-148. https://doi.org/10.1016/j.joca.2017.10.007
Jiang LB, et al. TIGAR Mediates the Inhibitory Role of Hypoxia On ROS Production and Apoptosis in Rat Nucleus Pulposus Cells. Osteoarthr Cartil. 2018;26(1):138-148. PubMed PMID: 29061494.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TIGAR mediates the inhibitory role of hypoxia on ROS production and apoptosis in rat nucleus pulposus cells. AU - Jiang,L-B, AU - Cao,L, AU - Ma,Y-Q, AU - Chen,Q, AU - Liang,Y, AU - Yuan,F-L, AU - Li,X-L, AU - Dong,J, AU - Chen,N, Y1 - 2017/10/20/ PY - 2017/04/02/received PY - 2017/10/07/revised PY - 2017/10/11/accepted PY - 2017/10/25/pubmed PY - 2018/8/14/medline PY - 2017/10/25/entrez KW - Hypoxia KW - Intervertebral disc degeneration KW - Nucleus pulposus KW - Reactive oxygen species KW - TP53-induced glycolysis and apoptosis regulator SP - 138 EP - 148 JF - Osteoarthritis and cartilage JO - Osteoarthr. Cartil. VL - 26 IS - 1 N2 - 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. SN - 1522-9653 UR - https://www.unboundmedicine.com/medline/citation/29061494/TIGAR_mediates_the_inhibitory_role_of_hypoxia_on_ROS_production_and_apoptosis_in_rat_nucleus_pulposus_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1063-4584(17)31251-7 DB - PRIME DP - Unbound Medicine ER -