Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Free radical biology & medicine, 2020-04, Vol.150, p.109-119

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2020

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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.