Autor: |
Tao Lan, Yu-chen Zheng, Ning-dao Li, Xiao-sheng Chen, Zhe Shen, Bin Yan |
Jazyk: |
angličtina |
Rok vydání: |
2021 |
Předmět: |
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Zdroj: |
Frontiers in Molecular Biosciences, Vol 8 (2021) |
Druh dokumentu: |
article |
ISSN: |
2296-889X |
DOI: |
10.3389/fmolb.2021.674632 |
Popis: |
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. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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