Berberine ameliorates oxidative stress-induced apoptosis by modulating ER stress and autophagy in human nucleus pulposus cells

Life Sciences ◽  
2019 ◽  
Vol 228 ◽  
pp. 85-97 ◽  
Author(s):  
Rongjin Luo ◽  
Zhiwei Liao ◽  
Yu Song ◽  
Huipeng Yin ◽  
Shengfeng Zhan ◽  
...  
Life Sciences ◽  
2018 ◽  
Vol 199 ◽  
pp. 122-130 ◽  
Author(s):  
Ruijun He ◽  
Min Cui ◽  
Hui Lin ◽  
Lei Zhao ◽  
Jiayu Wang ◽  
...  

2021 ◽  
Vol 8 ◽  
Author(s):  
Tao Lan ◽  
Yu-chen Zheng ◽  
Ning-dao Li ◽  
Xiao-sheng Chen ◽  
Zhe Shen ◽  
...  

ObjectiveThe aim of this study is to explore the role of Parkin in intervertebral disk degeneration (IDD) and its mitophagy regulation mechanism.Study design and methodsRat nucleus pulposus (NP) cells were stimulated with hydrogen peroxide (H2O2) to a mimic pathological condition. Apoptosis and mitophagy were assessed by Western blot, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and immunofluorescence staining. The CRISPR–dCas9–KRAB system was used to silence the expression of Parkin.ResultIn this study, we found that Parkin was downregulated in rat NP cells under oxidative stress. In addition, treatment with H2O2 resulted in mitochondrial dysfunction, autophagy inhibition, and a significant increase in the rate of apoptosis of NP cells. Meanwhile, mitophagy inhibition enhanced H2O2-induced apoptosis. Furthermore, repression of Parkin significantly attenuated mitophagy and exacerbated apoptosis.ConclusionThese results suggested that Parkin may play a protective role in alleviating the apoptosis of NP cells via mitophagy, and that targeting Parkin may provide a promising therapeutic strategy for the prevention of IDD.


2021 ◽  
Vol 2021 ◽  
pp. 1-22
Author(s):  
Huipeng Yin ◽  
Kun Wang ◽  
Abhirup Das ◽  
Gaocai Li ◽  
Yu Song ◽  
...  

The death of nucleus pulposus (NP) cells is an important cause of intervertebral disc (IVD) degeneration. Redox disturbance caused by dysfunctional mitochondria has been considered as a vital risk for NP cell survival. It is valuable to identify key proteins maintaining mitochondrial function in NP cells. A previous study found that regulated in development and DNA damage response 1 (REDD1) are upregulated during intervertebral disc degeneration and that REDD1 can cause NP cell apoptosis. Thus, the present study further explores the effect of REDD1 on IVD degeneration. Our results showed that REDD1 promotes NP cell apoptosis via the mitochondrial pathway. Importantly, REDD1 formed a complex with TXNIP to strengthen its own action, and the combination was consolidated under H2O2-induced oxidative stress. The combined inhibition of the REDD1/TXNIP complex was better than that of REDD1 or TXNIP alone in restoring cell proliferation and accelerating apoptosis. Moreover, p53 acts as the transcription factor of REDD1 to regulate the REDD1/TXNIP complex under oxidative stress. Altogether, our results demonstrated that the REDD1/TXNIP complex mediated H2O2-induced human NP cell apoptosis and IVD degeneration through the mitochondrial pathway. Interferences on these sites to achieve mitochondrial redox homeostasis may be a novel therapeutic strategy for oxidative stress-associated IVD degeneration.


2018 ◽  
Vol 27 (10) ◽  
pp. 2609-2620 ◽  
Author(s):  
Ming-Bo Guo ◽  
De-Chun Wang ◽  
Hai-Fei Liu ◽  
Long-Wei Chen ◽  
Jian-Wei Wei ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Qian Xiang ◽  
Zhangrong Cheng ◽  
Juntan Wang ◽  
Xiaobo Feng ◽  
Wenbin Hua ◽  
...  

Intervertebral disc degeneration (IDD) is one of the most common chronic degenerative musculoskeletal disorders. Oxidative stress-induced apoptosis of the nucleus pulposus (NP) cells plays a key role during IDD progression. Advanced oxidation protein products (AOPP), novel biomarkers of oxidative stress, have been reported to function in various diseases due to their potential for disrupting the redox balance. The current study is aimed at investigating the function of AOPP in the oxidative stress-induced apoptosis of human NP cells and the alleviative effects of allicin during this process which was known for its antioxidant properties. AOPP were demonstrated to hamper the viability and proliferation of NP cells in a time- and concentration-dependent manner and cause cell apoptosis markedly. High levels of reactive oxygen species (ROS) and lipid peroxidation product malondialdehyde (MDA) were detected in NP cells after AOPP stimulation, which resulted in depolarized mitochondrial transmembrane potential (MTP). Correspondingly, higher levels of AOPP were discovered in the human degenerative intervertebral discs (IVD). It was also found that allicin could protect NP cells against AOPP-mediated oxidative stress and mitochondrial dysfunction via suppressing the p38-MAPK pathway. These results disclosed a significant role of AOPP in the oxidative stress-induced apoptosis of NP cells, which could be involved in the primary pathogenesis of IDD. It was also revealed that allicin could be a promising therapeutic approach against AOPP-mediated oxidative stress during IDD progression.


2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Wenzheng Wang ◽  
Xiangcheng Qing ◽  
Baichuan Wang ◽  
Kaige Ma ◽  
Yulong Wei ◽  
...  

Tauroursodeoxycholic acid (TUDCA) is a kind of hydrophilic bile acid, which could protect cells from death via inhibiting endoplasmic reticulum (ER) stress. However, the role of TUDCA in compression-induced intervertebral disc degeneration (IVDD) has not been elucidated. Here, we used a previously described device to mimic in vivo compression conditions. NP cells treated with DMSO or TUDCA were exposed to compression. Then, cell viability, morphology, and apoptosis were detected. Furthermore, apoptosis-related proteins and necroptosis markers were detected too. To investigate the specific cytoprotective mechanisms of TUDCA in IVDD, we detected the ER morphology by electron microscopy. In addition, the ER stress of nucleus pulposus (NP) cells was quantitatively evaluated by analyzing the level of ER-stress-associated proteins. Our results revealed that TUDCA could protect NP cells from excessive compression-induced death by reducing the apoptosis and necroptosis. In addition, ER stress is involved in pathogenesis of IVDD induced by excessive compression and plays a detrimental role. TUDCA exerts its protective functions by inhibiting ER stress. In conclusion, TUDCA could protect NP cells from compression-induced death, which suggested that treatment by TUDCA may be a potential method to retard IVDD.


2018 ◽  
Vol 46 (07) ◽  
pp. 1561-1580 ◽  
Author(s):  
Zengjie Zhang ◽  
Chenggui Wang ◽  
Jialiang Lin ◽  
Haiming Jin ◽  
Ke Wang ◽  
...  

Intervertebral disc degeneration (IDD) is a major cause of lower back pain, but few efficacious medicines have been developed for IDD. Increased nucleus pulposus cells apoptosis is a dominant pathogenesis of IDD and is considered a therapeutic target. Previously, our group proved that autophagy may protect nucleus pulposus cells against apoptosis. As one of the major bioflavonoids of citrus, naringin activates autophagy. Therefore, we hypothesize that naringin may have therapeutic potential for IDD by activating autophagy in nucleus pulposus cells. In this study, we evaluated the effects of naringin on TBHP-induced oxidative stress in nucleus pulposus cells in vitro as well as in puncture-induced rat IDD model in vivo. Our results showed that naringin could reduce the incidence of oxidative stress-induced apoptosis in nucleus pulposus cells and promoted the expression of autophagy markers LC3-II/I and beclin-1. Meanwhile, inhibition of autophagy by 3-MA may partially reverse the anti-apoptotic effect of naringin, indicating that autophagy was involved in the protective effect of naringin in nucleus pulposus cells. Further study showed that autophagy regulation of naringin may be related to AMPK signaling. Also, we found that naringin treatment can regulate the expression of collagen II, aggrecan and Mmp13 to sustain the extracellular matrix. Furthermore, our in vivo study showed that naringin can ameliorate IDD in puncture-induced rat model. In conclusion, our study suggests that naringin can protect nucleus pulposus cells against apoptosis and ameliorate IDD in vivo, the mechanism may relate to its autophagy regulation.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yiqiang Hu ◽  
Ranyang Tao ◽  
Linfang Wang ◽  
Lang Chen ◽  
Ze Lin ◽  
...  

Oxidative stress is relevant in compression-induced nucleus pulposus (NP) cell apoptosis and intervertebral disc (IVD) degeneration. Exosomes derived from bone mesenchymal stem cells (BMSCs-Exos) are key secretory products of MSCs, with important roles in tissue regeneration. This research is aimed at studying the protective impact of BMSCs-Exos on NP cell apoptosis caused by compression and investigating the underlying mechanisms. Our results indicated that we isolated BMSCs successfully. Exosomes were isolated from the BMSCs and found to alleviate the inhibitory effect that compression has on proliferation and viability in NP cells, decreasing the toxic effects of compression-induced NP cells. AnnexinV/PI double staining and TUNEL assays indicated that the BMSCs-Exos reduced compression-induced apoptosis. In addition, our research found that BMSCs-Exos suppressed compression-mediated NP oxidative stress by detecting the ROS and malondialdehyde level. Furthermore, BMSCs-Exos increased the mitochondrial membrane potential and alleviated compression-induced mitochondrial damage. These results indicate that BMSCs-Exos alleviate compression-mediated NP apoptosis by suppressing oxidative stress, which may provide a promising cell-free therapy for treating IVD degeneration.


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