title: The responses of autophagy and apoptosis to oxidative stress in nucleus pulposus cells: implications for disc degeneration.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Orthopedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Jiang-Wei
authors.initials: JW
authors.lastname: Chen
authors.forename: Bin-Bin
authors.initials: BB
authors.lastname: Ni
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.forename: Yue-Hua
authors.initials: YH
authors.lastname: Yang
authors.forename: Sheng-Dan
authors.initials: SD
authors.lastname: Jiang
authors.forename: Lei-Sheng
authors.initials: LS
authors.lastname: Jiang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007403:Intervertebral Disc / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D055959:Intervertebral Disc Degeneration / Q000378:metabolism / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D006861:Hydrogen Peroxide; D058570:TOR Serine-Threonine Kinases