Upregulation of SIRT1 ameliorates apoptosis of rat nucleus pulposus cells under oxidative stress through FoxO1/β-catenin pathway.

IF 1.7 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Hongtao Hu, Sheng Wang, Haijun Teng, Sishun Zhao, Weisheng Hong
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引用次数: 0

Abstract

Introduction: Age-related degenerative changes in intervertebral discs (IVDs) can lead to lower back pain, and even paralysis. This topic is therefore garnering growing attention in an increasingly ageing society. The oxidative stress-induced degenerative process is a major contributor to apoptosis in nucleus pulposus cells. However, the regulatory mechanism of NAD-dependent protein deacetylase Sirtuin-1 (SIRT1) on apoptosis in oxidative stress-induced rat nucleus pulposus cells remains unclear.

Material and methods: Rat nucleus pulposus cells (NPCs) were induced to undergo degenerative changes through H₂O₂ exposure, simulating the ageing oxidative stress process. Subsequently, the SIRT1 activator SRT2104 was employed to explore the impact of SIRT1 on the expression of markers of ageing oxidative stress process in NPCs. The FoxO1 inhibitor AS1842856 was used to investigate the role of the downstream signalling pathway FoxO1/β-catenin in ageing NPCs under the influence of SRT2104. TUNEL staining and other assays such as CCK were used to observe the effects of H₂O₂ on cell apoptosis and viability, respectively. The influence of the aforementioned treatments on the ageing phenotype was observed through β-galactosidase staining, immunofluorescence staining, flow cytometry analysis, and protein electrophoresis.

Results: Under H₂O₂-induced oxidative stress, both the mRNA and protein levels of SIRT1 decreased in rat NPCs. Conversely, specific activation of SIRT1 inhibited apoptosis and reduced the expression of senescence-associated secretoryphenotype (SASP) and ageing-related proteins. Meanwhile, inhibiting FoxO1 expression with AS1842856 significantly upregulated β-catenin protein levels, suppressing the apoptosis process in ageing NPCs under oxidative stress.

Conclusions: These results suggest that activation of the SIRT1/FoxO1/β-Catenin axis can diminish ageing-related phenotypes and cell apoptosis in NPCs, inhibiting the oxidative stress-induced ageing process triggered by H₂O₂. These findings may offer a new perspective for the treatment of intervertebral disc degeneration (IDD) in the future.

上调SIRT1通过FoxO1/β-catenin通路改善氧化应激下大鼠髓核细胞凋亡。
年龄相关的椎间盘退行性改变(IVDs)可导致腰痛,甚至瘫痪。因此,这个话题在日益老龄化的社会中越来越受到关注。氧化应激诱导的退行性过程是髓核细胞凋亡的主要原因。然而,nad依赖性蛋白去乙酰化酶Sirtuin-1 (SIRT1)对氧化应激诱导的大鼠髓核细胞凋亡的调控机制尚不清楚。材料与方法:通过H₂O₂暴露诱导大鼠髓核细胞(NPCs)发生退行性改变,模拟老化氧化应激过程。随后,我们利用SIRT1激活剂SRT2104来探讨SIRT1对npc中老化氧化应激过程标志物表达的影响。利用FoxO1抑制剂AS1842856研究下游信号通路FoxO1/β-catenin在SRT2104影响下衰老npc中的作用。通过TUNEL染色和CCK等方法分别观察h2o2对细胞凋亡和细胞活力的影响。通过β-半乳糖苷酶染色、免疫荧光染色、流式细胞术分析和蛋白电泳观察上述处理对衰老表型的影响。结果:在h2o2诱导的氧化应激下,大鼠NPCs中SIRT1 mRNA和蛋白水平均下降。相反,特异性激活SIRT1抑制细胞凋亡,降低衰老相关分泌表型(SASP)和衰老相关蛋白的表达。同时,用AS1842856抑制FoxO1表达可显著上调β-catenin蛋白水平,抑制氧化应激下老化npc的凋亡过程。结论:这些结果表明SIRT1/FoxO1/β-Catenin轴的激活可以减少NPCs中与衰老相关的表型和细胞凋亡,抑制h2o2引发的氧化应激诱导的衰老过程。这些发现可能为将来椎间盘退变(IDD)的治疗提供新的视角。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Folia histochemica et cytobiologica
Folia histochemica et cytobiologica 生物-生化与分子生物学
CiteScore
2.80
自引率
6.70%
发文量
56
审稿时长
6-12 weeks
期刊介绍: "Folia Histochemica et Cytobiologica" is an international, English-language journal publishing articles in the areas of histochemistry, cytochemistry and cell & tissue biology. "Folia Histochemica et Cytobiologica" was established in 1963 under the title: ‘Folia Histochemica et Cytochemica’ by the Polish Histochemical and Cytochemical Society as a journal devoted to the rapidly developing fields of histochemistry and cytochemistry. In 1984, the profile of the journal was broadened to accommodate papers dealing with cell and tissue biology, and the title was accordingly changed to "Folia Histochemica et Cytobiologica". "Folia Histochemica et Cytobiologica" is published quarterly, one volume a year, by the Polish Histochemical and Cytochemical Society.
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