期刊
MOLECULAR BIOLOGY REPORTS
卷 49, 期 5, 页码 3783-3792出版社
SPRINGER
DOI: 10.1007/s11033-022-07218-2
关键词
Intervertebral disc degeneration; GSK-3 beta; SB216763; Nucleus pulposus cells; Oxidative stress; Apoptosis
资金
- National Key Research and Development Program of China [2016YFA0101300]
This study found that the GSK-3 beta inhibitor has a protective effect on NP cells against apoptosis under oxidative stress, mainly through protecting the mitochondrial membrane potential, inhibiting the expression of apoptosis-related proteins, and ultimately reducing cell apoptosis.
Background Oxidative stress in the intervertebral disc leads to nucleus pulposus (NP) degeneration by inducing cell apoptosis. However, the molecular mechanisms underlying this process remain unclear. Increasing evidence indicates that GSK-3 beta is related to cell apoptosis induced by oxidative stress. In this study, we explored whether GSK-3 beta inhibition protects human NP cell against apoptosis under oxidative stress. Methods and results Immunofluorescence staining was used to show the expression of GSK-3 beta in human NP cells (NPCs). Flow cytometry, mitochondrial staining and western blot (WB) were used to detect apoptosis of treated NPCs, changes of mitochondrial membrane potential and the expression of mitochondrial apoptosis-related proteins using GSK-3 beta specific inhibitor SB216763. Co-Immunoprecipitation (Co-IP) was used to demonstrate the interaction between GSK-3 beta and Bcl-2. We delineated the protective effect of GSK-3 beta specific inhibitor SB216763 on human NPCs apoptosis induced by oxidative stress in vitro. Further, we showed SB216763 exert the protective effect by preservation of the mitochondrial membrane potential and inhibition of caspase 3/7 activity during oxidative injury. The detailed mechanism underlying the antiapoptotic effect of GSK-3 beta inhibition was also studied by analyzing mitochondrial apoptosis pathway in vitro. Conclusions We concluded that the GSK-3 beta inhibitor SB216763 protected mitochondrial membrane potential to delay nucleus pulposus cell apoptosis by inhibiting the interaction between GSK-3 beta and Bcl-2 and subsequently reducing cytochrome c(Cyto-C) release and caspase-3 activation. Together, inhibition of GSK-3 beta using SB216763 in NPCs may be a favorable therapeutic strategy to slow intervertebral disc degeneration.
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