scholarly journals CRISPR/dCas9-Mediated Parkin Inhibition Impairs Mitophagy and Aggravates Apoptosis of Rat Nucleus Pulposus Cells Under Oxidative Stress

2021 ◽  
Vol 8 ◽  
Author(s):  
Tao Lan ◽  
Yu-chen Zheng ◽  
Ning-dao Li ◽  
Xiao-sheng Chen ◽  
Zhe Shen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nucleus Pulposus ◽  
Pathological Condition ◽  
Protective Role ◽  
Intervertebral Disk ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Regulation Mechanism ◽  
Nucleus Pulposus Cells ◽  
Induced Apoptosis ◽  
Design And Methods

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.

Melatonin resists oxidative stress-induced apoptosis in nucleus pulposus cells

Life Sciences ◽  
2018 ◽  
Vol 199 ◽  
pp. 122-130 ◽  
Author(s):  
Ruijun He ◽  
Min Cui ◽  
Hui Lin ◽  
Lei Zhao ◽  
Jiayu Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nucleus Pulposus ◽  
Nucleus Pulposus Cells ◽  
Induced Apoptosis

scholarly journals The REDD1/TXNIP Complex Accelerates Oxidative Stress-Induced Apoptosis of Nucleus Pulposus Cells through the Mitochondrial Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-22
Author(s):  
Huipeng Yin ◽  
Kun Wang ◽  
Abhirup Das ◽  
Gaocai Li ◽  
Yu Song ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Cell Apoptosis ◽  
Redox Homeostasis ◽  
Mitochondrial Pathway ◽  
Nucleus Pulposus Cells ◽  
Damage Response ◽  
Induced Apoptosis ◽  
Ivd Degeneration

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.

Lupeol against high-glucose-induced apoptosis via enhancing the anti-oxidative stress in rabbit nucleus pulposus cells

2018 ◽  
Vol 27 (10) ◽  
pp. 2609-2620 ◽  
Author(s):  
Ming-Bo Guo ◽  
De-Chun Wang ◽  
Hai-Fei Liu ◽  
Long-Wei Chen ◽  
Jian-Wei Wei ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nucleus Pulposus ◽  
High Glucose ◽  
Nucleus Pulposus Cells ◽  
Induced Apoptosis

scholarly journals Allicin Attenuated Advanced Oxidation Protein Product-Induced Oxidative Stress and Mitochondrial Apoptosis in Human Nucleus Pulposus Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Qian Xiang ◽  
Zhangrong Cheng ◽  
Juntan Wang ◽  
Xiaobo Feng ◽  
Wenbin Hua ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nucleus Pulposus ◽  
Mapk Pathway ◽  
Antioxidant Properties ◽  
Advanced Oxidation ◽  
Dependent Manner ◽  
Lipid Peroxidation Product ◽  
Nucleus Pulposus Cells ◽  
Promising Therapeutic Approach ◽  
Induced Apoptosis

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.

scholarly journals Tea Polyphenol Attenuates Oxidative Stress-Induced Degeneration of Intervertebral Discs by Regulating the Keap1/Nrf2/ARE Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Dawei Song ◽  
Jun Ge ◽  
Yingjie Wang ◽  
Qi Yan ◽  
Cenhao Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Intervertebral Discs ◽  
Protective Role ◽  
In Vivo Model ◽  
Nucleus Pulposus Cells ◽  
Public Attention

Objective. Intervertebral disc degeneration (IDD) and low back pain caused by IDD have attracted public attention owing to their extremely high incidence and disability rate. Oxidative stress is a major cause of IDD. Tea polyphenols (TP) are natural-derived antioxidants extracted from tea leaves. This study explored the protective role of TP on the nucleus pulposus cells (NPCs) of intervertebral discs and their underlying mechanism. Methods. An in vitro model of H2O2-induced degeneration of NPCs was established. RT-qPCR and western blotting were used to detect the mRNA and protein expression of the targets. An in vivo model of IDD was established via acupuncture of the intervertebral disc. Radiological imaging and histological staining were performed to evaluate the protective role of TP. Results. H2O2 contributed to NPC degeneration by inducing high levels of oxidative stress. TP treatment effectively increased the expression of nucleus pulposus matrix-associated genes and reduced the expression of degeneration factors. Further mechanistic studies showed that TP delayed H2O2-mediated NPC degeneration by activating the Keap1/Nrf2/ARE pathway. In vivo experiments showed that TP delayed the degeneration of NPCs in rats through the Keap1/Nrf2/ARE pathway. Conclusion. Our study confirmed that TP activates the Keap1/Nrf2/ARE pathway to exert an antioxidative stress role, ultimately delaying the degeneration of intervertebral discs.

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 ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Er Stress ◽  
Nucleus Pulposus ◽  
Nucleus Pulposus Cells ◽  
Induced Apoptosis

Therapeutic Potential of Naringin for Intervertebral Disc Degeneration: Involvement of Autophagy Against Oxidative Stress-Induced Apoptosis in Nucleus Pulposus Cells

2018 ◽  
Vol 46 (07) ◽  
pp. 1561-1580 ◽  
Author(s):  
Zengjie Zhang ◽  
Chenggui Wang ◽  
Jialiang Lin ◽  
Haiming Jin ◽  
Ke Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Therapeutic Potential ◽  
Nucleus Pulposus Cells ◽  
Induced Apoptosis

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.

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