The Responses of Autophagy and Apoptosis to Oxidative Stress in Nucleus Pulposus Cells: Implications for Disc Degeneration

Cellular Physiology and Biochemistry

关键词: Oxidative stress;    Autophagy;    Apoptosis;    ERK;    Nucleus pulposus cells;   

DOI  :  10.1159/000366330

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background/Aims Apoptosis and autophagy are two patterns of programmed cell death which play important roles in the intervertebral disc degeneration. Oxidative stress is an important factor for the induction of programmed cell death. However, the cellular reactions linking autophagy to apoptosis of disc cells under oxidative stress have never been described. This study investigated the responses of autophagy and apoptosis and their interactions in the nucleus pulposus cells (NP cells) under oxidative stress, with the aim to better understand the mechanism of disc degeneration. Methods NP cells isolated from rat lumbar discs were subjected to different concentrations of H₂O₂ for various time periods. Cell viability was determined by CCK-8 assay, and their apoptosis and autophagy responses were evaluated by fluorescent analysis, flow cytometry and western blotting, et al. The interactions of autophagy and apoptosis and the possible signaling pathways were also investigated by using autophagy modulators. Results H₂O₂ increased the lysosomal membrane permeability in the NP cells and induced apoptosis through the mitochondrial pathway subsequently. Meanwhile, H₂O₂ stimulated an early autophagy response through the ERK/m-TOR signaling pathway. Autophagy inhibition significantly decreased the apoptosis incidence in the cells insulted by H₂O₂. Conclusion These results suggested that controlling the autophagy response in the NP cells under oxidative stress should be beneficial for the survival of the cells and probably delay the process of disc degeneration.

【 授权许可】

CC BY-NC-ND