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

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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 nutrientsensitive protein Bcell lymphoma 2/adenovirus E1B 19 kDainteracting protein (BNIP3) and the mitochondrial prodeath protein apoptosisinducing 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 timedependent 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 NDinduced NP cell death, whereas knockdown of BNIP3 or AIF abolished NDinduced 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 NDinduced death of NP cells during disc degeneration.
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Document Type: Research Article

Affiliations: 1: Department of Orthopaedics, The First People's Hospital of Yunnan, Kunming, Yunnan 650032, P.R. China 2: Department of Orthopaedics, Xinqiao Hospital, The Third Military Medical University, Chongqing 400038, P.R. China

Publication date: January 1, 2017

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  • Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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