Restoration of Autophagic Flux Rescues Oxidative Damage and Mitochondrial Dysfunction to Protect against Intervertebral Disc Degeneration
Joint Authors
Kang, Liang
Xiang, Qian
Zhan, Shengfeng
Song, Yu
Wang, Kun
Zhao, Kangcheng
Li, Shuai
Shao, Zengwu
Yang, Cao
Zhang, Yukun
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-27, 27 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-12-30
Country of Publication
Egypt
No. of Pages
27
Main Subjects
Abstract EN
Oxidative stress-induced mitochondrial dysfunction and nucleus pulposus (NP) cell apoptosis play crucial roles in the development of intervertebral disc degeneration (IDD).
Increasing studies have shown that interventions targeting impaired autophagic flux can maintain cellular homeostasis by relieving oxidative damage.
Here, we investigated the effect of curcumin (CUR), a known autophagy activator, on IDD in vitro and in vivo.
CUR suppressed tert-butyl hydroperoxide- (TBHP-) induced oxidative stress and mitochondrial dysfunction and thereby inhibited human NP cell apoptosis, senescence, and ECM degradation.
CUR treatment induced autophagy and enhanced autophagic flux in an AMPK/mTOR/ULK1-dependent manner.
Notably, CUR alleviated TBHP-induced interruption of autophagosome-lysosome fusion and impairment of lysosomal function and thus contributed to the restoration of blocked autophagic clearance.
These protective effects of CUR in TBHP-stimulated human NP cells resembled the effects produced by the autophagy inducer rapamycin, but the effects were partially eliminated by 3-methyladenine- and compound C-mediated inhibition of autophagy initiation or chloroquine-mediated obstruction of autophagic flux.
Lastly, CUR also exerted a protective effect against puncture-induced IDD progression in vivo.
Our results showed that suppression of excessive ROS production and mitochondrial dysfunction through enhancement of autophagy coupled with restoration of autophagic flux ameliorated TBHP-induced human NP cell apoptosis, senescence, and ECM degradation.
Thus, maintenance of the proper functioning of autophagy represents a promising therapeutic strategy for IDD, and CUR might serve as an effective therapeutic agent for IDD.
American Psychological Association (APA)
Kang, Liang& Xiang, Qian& Zhan, Shengfeng& Song, Yu& Wang, Kun& Zhao, Kangcheng…[et al.]. 2019. Restoration of Autophagic Flux Rescues Oxidative Damage and Mitochondrial Dysfunction to Protect against Intervertebral Disc Degeneration. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-27.
https://search.emarefa.net/detail/BIM-1205255
Modern Language Association (MLA)
Kang, Liang…[et al.]. Restoration of Autophagic Flux Rescues Oxidative Damage and Mitochondrial Dysfunction to Protect against Intervertebral Disc Degeneration. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-27.
https://search.emarefa.net/detail/BIM-1205255
American Medical Association (AMA)
Kang, Liang& Xiang, Qian& Zhan, Shengfeng& Song, Yu& Wang, Kun& Zhao, Kangcheng…[et al.]. Restoration of Autophagic Flux Rescues Oxidative Damage and Mitochondrial Dysfunction to Protect against Intervertebral Disc Degeneration. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-27.
https://search.emarefa.net/detail/BIM-1205255
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1205255