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TIGAR impedes compression-induced intervertebral disc degeneration by suppressing nucleus pulposus cell apoptosis and autophagy.

Abstract

To investigate whether TP53-induced glycolysis and apoptosis regulator (TIGAR) participates in compression-induced intervertebral disc (IVD) degeneration, and to determine the regulatory effect of TIGAR on nucleus pulposus (NP) cell autophagy and apoptosis following compression-induced injuries. IVD tissues were collected from human patients undergoing surgery (n = 20) and skeletally mature Sprague-Dawley rats (n = 15). Initially, the effect of compression on the expression of TIGAR was evaluated with in vivo and in vitro models. In addition, TIGAR was silenced to investigate the regulatory effect of TIGAR on compression-induced intracellular reactive oxygen species (ROS) levels, autophagy, and apoptosis in rat NP cells. Furthermore, the P53 inhibitor pifithrin-α (PFTα) and SP1 inhibitor mithramycin A were employed to detect expression level changes of TIGAR and autophagy-associated target molecules. TIGAR expression of NP cells increased gradually in human degenerative IVDs and in rat NP cells under compression both in vivo and in vitro. TIGAR knockdown enhanced compression-induced intracellular ROS generation and the NADPH/NADP+ and GSH/GSSG ratios. Moreover, TIGAR knockdown amplified the compression-induced caspase-3 activation and the apoptosis rate of rat NP cells. Likewise, knockdown of TIGAR significantly accelerated LC3B expression and autophagosome formation in rat NP cells during compression-induced injuries. The results also established that mithramycin A could inhibit TIGAR expression and autophagy levels in NP cells under compression conditions, while PFTα had no similar effect. Our data demonstrated that TIGAR acted as an important endogenous negative regulator of ROS levels, which might inhibit compression-induced apoptosis and autophagy through SP1-dependent mechanisms.

Authors+Show Affiliations

Department of Orthopaedics, Renmin Hospital of Wuhan University, Wuhan, China.Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31317559

Citation

Li, Zhiliang, et al. "TIGAR Impedes Compression-induced Intervertebral Disc Degeneration By Suppressing Nucleus Pulposus Cell Apoptosis and Autophagy." Journal of Cellular Physiology, 2019.
Li Z, Shao Z, Chen S, et al. TIGAR impedes compression-induced intervertebral disc degeneration by suppressing nucleus pulposus cell apoptosis and autophagy. J Cell Physiol. 2019.
Li, Z., Shao, Z., Chen, S., Huang, D., Peng, Y., Chen, S., & Ma, K. (2019). TIGAR impedes compression-induced intervertebral disc degeneration by suppressing nucleus pulposus cell apoptosis and autophagy. Journal of Cellular Physiology, doi:10.1002/jcp.29097.
Li Z, et al. TIGAR Impedes Compression-induced Intervertebral Disc Degeneration By Suppressing Nucleus Pulposus Cell Apoptosis and Autophagy. J Cell Physiol. 2019 Jul 17; PubMed PMID: 31317559.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TIGAR impedes compression-induced intervertebral disc degeneration by suppressing nucleus pulposus cell apoptosis and autophagy. AU - Li,Zhiliang, AU - Shao,Zengwu, AU - Chen,Songfeng, AU - Huang,Donghua, AU - Peng,Yizhong, AU - Chen,Sheng, AU - Ma,Kaige, Y1 - 2019/07/17/ PY - 2019/03/31/received PY - 2019/06/27/accepted PY - 2019/7/19/entrez KW - TIGAR KW - apoptosis KW - autophagy KW - compression KW - intervertebral disc degeneration KW - reactive oxygen species JF - Journal of cellular physiology JO - J. Cell. Physiol. N2 - To investigate whether TP53-induced glycolysis and apoptosis regulator (TIGAR) participates in compression-induced intervertebral disc (IVD) degeneration, and to determine the regulatory effect of TIGAR on nucleus pulposus (NP) cell autophagy and apoptosis following compression-induced injuries. IVD tissues were collected from human patients undergoing surgery (n = 20) and skeletally mature Sprague-Dawley rats (n = 15). Initially, the effect of compression on the expression of TIGAR was evaluated with in vivo and in vitro models. In addition, TIGAR was silenced to investigate the regulatory effect of TIGAR on compression-induced intracellular reactive oxygen species (ROS) levels, autophagy, and apoptosis in rat NP cells. Furthermore, the P53 inhibitor pifithrin-α (PFTα) and SP1 inhibitor mithramycin A were employed to detect expression level changes of TIGAR and autophagy-associated target molecules. TIGAR expression of NP cells increased gradually in human degenerative IVDs and in rat NP cells under compression both in vivo and in vitro. TIGAR knockdown enhanced compression-induced intracellular ROS generation and the NADPH/NADP+ and GSH/GSSG ratios. Moreover, TIGAR knockdown amplified the compression-induced caspase-3 activation and the apoptosis rate of rat NP cells. Likewise, knockdown of TIGAR significantly accelerated LC3B expression and autophagosome formation in rat NP cells during compression-induced injuries. The results also established that mithramycin A could inhibit TIGAR expression and autophagy levels in NP cells under compression conditions, while PFTα had no similar effect. Our data demonstrated that TIGAR acted as an important endogenous negative regulator of ROS levels, which might inhibit compression-induced apoptosis and autophagy through SP1-dependent mechanisms. SN - 1097-4652 UR - https://www.unboundmedicine.com/medline/citation/31317559/TIGAR_impedes_compression-induced_intervertebral_disc_degeneration_by_suppressing_nucleus_pulposus_cell_apoptosis_and_autophagy L2 - https://doi.org/10.1002/jcp.29097 DB - PRIME DP - Unbound Medicine ER -