Neuroprotective role of BNIP3 under oxidative stress through autophagy in neuroblastoma cells

Mol Biol Rep. 2014 Sep;41(9):5729-34. doi: 10.1007/s11033-014-3444-7. Epub 2014 Jun 14.

Abstract

Reactive oxygen species (ROS) are produced due to oxidative stress which has wide range of affiliation with different diseases including cancer, heart failure, diabetes and neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, ischemic and hemorrhagic diseases. This study shows the involvement of BNIP3 in the amplification of metabolic pathways related to cellular quality control and cellular self defence mechanism in the form of autophagy. We used conventional methods to induce autophagy by treating the cells with H2O2. MTT assay was performed to observe the cellular viability in stressed condition. MDC staining was carried out for detection of autophagosomes formation which confirmed the autophagy. Furthermore, expression of BNIP3 was validated by western blot analysis with LC3 antibody. From these results it is clear that BNIP3 plays a key role in defence mechanism by removing the misfolded proteins through autophagy. These results enhance the practical application of BNIP3 in neuroblastoma cells and are helpful in reducing the chances of neurodegenerative diseases. Although, the exact mode of action is still unknown but these findings unveil a molecular mechanism for the role of autophagy in cell death and provide insight into complex relationship between ROS and non-apoptotic programmed cell death.

MeSH terms

  • Apoptosis
  • Autophagy / drug effects*
  • Cell Line, Tumor
  • Cell Survival
  • Humans
  • Hydrogen Peroxide / adverse effects
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Neuroblastoma / metabolism
  • Neuroblastoma / pathology*
  • Oxidative Stress*
  • Plasmids / genetics
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Reactive Oxygen Species / metabolism

Substances

  • BNIP3 protein, human
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • Reactive Oxygen Species
  • Hydrogen Peroxide