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营养剥夺通过激活 BNIP3/AIF 信号通路诱导髓核细胞凋亡。

Nutrient deprivation induces apoptosis of nucleus pulposus cells via activation of the BNIP3/AIF signalling pathway.

机构信息

Department of Orthopaedics, The First People's Hospital of Yunnan, Kunming, Yunnan 650032, P.R. China.

Department of Orthopaedics, Xinqiao Hospital, The Third Military Medical University, Chongqing 400038, P.R. China.

出版信息

Mol Med Rep. 2017 Nov;16(5):7253-7260. doi: 10.3892/mmr.2017.7550. Epub 2017 Sep 20.

Abstract

Nutrient deprivation (ND)‑induced nucleus pulposus (NP) cell death serves an important role in intervertebral disc degeneration disease. However, the underlying mechanisms have yet to be thoroughly elucidated. The present study created a cell culture model under ND conditions to investigate the roles of the nutrient‑sensitive protein B‑cell lymphoma 2/adenovirus E1B 19 kDa‑interacting protein (BNIP3) and the mitochondrial pro‑death protein apoptosis‑inducing factor (AIF) in the death pathway of NP cells. The present study demonstrated that cells subjected to ND for up to 72 h exhibited a time‑dependent increase in cell death and decrease in mitochondrial membrane potential (Δψm), as compared with cells cultured under normal conditions. The results of western blotting demonstrated that BNIP3 expression was significantly upregulated in NP cells subjected to ND for 24 h, which coincided with AIF translocation to the cell nucleus and alterations in cell viability and Δψm. Furthermore, BNIP3 overexpression increased ND‑induced NP cell death, whereas knockdown of BNIP3 or AIF abolished ND‑induced NP cell death. In addition, BNIP3 overexpression increased AIF expression and BNIP3 knockdown decreased AIF expression in NP cells subjected to ND. In conclusion, ND induced NP cell death partially via activation of the BNIP3/AIF signalling pathway. These findings provide novel insights into the potential mechanisms underlying ND‑induced death of NP cells during disc degeneration.

摘要

营养剥夺(ND)诱导的核髓核(NP)细胞死亡在椎间盘退行性疾病中起着重要作用。然而,其潜在的机制尚未得到充分阐明。本研究在 ND 条件下创建了细胞培养模型,以研究营养敏感蛋白 B 细胞淋巴瘤 2/腺病毒 E1B 19 kDa 相互作用蛋白(BNIP3)和线粒体促死亡蛋白凋亡诱导因子(AIF)在 NP 细胞死亡途径中的作用。本研究表明,与正常培养条件下的细胞相比,ND 处理长达 72 h 的细胞表现出时间依赖性的细胞死亡增加和线粒体膜电位(Δψm)降低。Western blot 结果表明,ND 处理 24 h 的 NP 细胞中 BNIP3 表达显著上调,同时 AIF 向细胞核易位以及细胞活力和 Δψm 发生改变。此外,BNIP3 过表达增加了 ND 诱导的 NP 细胞死亡,而 BNIP3 敲低或 AIF 敲除则消除了 ND 诱导的 NP 细胞死亡。此外,BNIP3 过表达增加了 ND 处理的 NP 细胞中 AIF 的表达,而 BNIP3 敲低则降低了 AIF 的表达。总之,ND 通过激活 BNIP3/AIF 信号通路诱导 NP 细胞死亡。这些发现为椎间盘退变过程中 ND 诱导的 NP 细胞死亡的潜在机制提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a84/5865853/c2c07139dbcd/mmr-16-05-7253-g00.jpg

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