自噬
小檗碱
氧化应激
细胞凋亡
细胞生物学
活力测定
程序性细胞死亡
化学
药理学
生物
生物化学
作者
Rongjin Luo,Zhiwei Liao,Yu Song,Huipeng Yin,Shengfeng Zhan,Gaocai Li,Liang Ma,Shuaicheng Lu,Kun Wang,Shuai Li,Yukun Zhang,Cao Yang
出处
期刊:Life Sciences
[Elsevier]
日期:2019-07-01
卷期号:228: 85-97
被引量:68
标识
DOI:10.1016/j.lfs.2019.04.064
摘要
Nucleus pulposus (NP) cell apoptosis induced by oxidative stress is known to be closely involved in the pathogenesis of intervertebral disc (IVD) degeneration. Berberine, a small molecule derived from Rhizoma coptidis, has been found to exert antioxidative activity and preserve cell viability. The present study aims to investigate whether berberine can prevent NP cell apoptosis under oxidative damage and the potential underlying mechanisms. The effects of berberine on IVD degeneration were investigated both in vitro and in vivo. Our results showed that berberine significantly mitigated oxidative stress-decreased cell viability as well as apoptosis in human NP cells. Berberine treatment could attenuate oxidative stress-induced ER stress and autophagy in a concentration-dependent manner. With 4-PBA (ER stress specific inhibitor) and 3-MA (autophagy specific inhibitor) administration, we demonstrated that berberine inhibited oxidative stress-induced apoptosis by modulating the ER stress and autophagy pathway. We also found that the IRE1/JNK pathway was involved in the induction of ER stress-dependent autophagy. With Ca2+ chelator BAPTA-AM utilization, we revealed that oxidative stress-mediated ER stress and autophagy repressed by berberine could be restored by inducing intracellular Ca2+ dysregulation. Furthermore, in vivo study provided evidence that berberine treatment could retard the process of puncture-induced IVD degeneration in a rat model. Our results indicate that berberine could prevent oxidative stress-induced apoptosis by modulating ER stress and autophagy, thus offering a novel potential pharmacological treatment strategy for IVD degeneration.
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