Urolithin A-induced mitophagy suppresses apoptosis and attenuates intervertebral disc degeneration via the AMPK signaling pathway

Intervertebral disc degeneration (IDD) is a major cause of low back pain (LBP), and effective therapies are still lacking. Previous studies reported that mitochondrial dysfunction contributes to apoptosis, and urolithin A (UA) specifically induces mitophagy. Herein, we aimed to investigate the prote...

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Published in:Free radical biology & medicine 2020-04, Vol.150, p.109-119
Main Authors: Lin, Jialiang, Zhuge, Jinru, Zheng, Xuanqi, Wu, Yuhao, Zhang, Zengjie, Xu, Tianzhen, Meftah, Zaher, Xu, Hongming, Wu, Yaosen, Tian, Naifeng, Gao, Weiyang, Zhou, Yifei, Zhang, Xiaolei, Wang, Xiangyang
Format: Article
Language:English
Subjects:
AMPK
Apoptosis
Intervertebral disc degeneration
Mitophagy
Urolithin A
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Summary:Intervertebral disc degeneration (IDD) is a major cause of low back pain (LBP), and effective therapies are still lacking. Previous studies reported that mitochondrial dysfunction contributes to apoptosis, and urolithin A (UA) specifically induces mitophagy. Herein, we aimed to investigate the protective effect of UA-induced mitophagy on tert-butyl hydroperoxide (TBHP)-induced apoptosis in nucleus pulposus (NP) cells in vitro and a rat model of IDD in vivo. Mitochondrial function, apoptosis, and mitophagy were measured in UA-treated NP cells by western blotting and immunofluorescence; the therapeutic effects of UA on IDD were assessed in rats with puncture-induced IDD. The results showed that UA could activate mitophagy in primary NP cells, and UA treatment inhibited TBHP-induced mitochondrial dysfunction and the intrinsic apoptosis pathway. Mechanistically, we revealed that UA promoted mitophagy by activating AMPK signaling in TBHP-induced NP cells. In vivo, UA was shown to effectively alleviate the progression of puncture-induced IDD in rats. Taken together, our results suggest that UA could be a novel and effective therapeutic strategy for IDD. [Display omitted] •Urolithin A could induce mitophagy in primary NP cells.•Urolithin A attenuated TBHP-induced apoptosis and mitochondrial dysfunction in NP cells by activation of mitophagy.•The protective effects of Urolithin A both in vitro and in vivo were involved in AMPK activation.
ISSN:0891-5849
1873-4596
DOI:10.1016/j.freeradbiomed.2020.02.024