Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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NELL2 Function in the Protection of Cells against Endoplasmic Reticulum Stress

  • Kim, Dong Yeol (Department of Biological Sciences, College of Natural Sciences, University of Ulsan) ;
  • Kim, Han Rae (Department of Biological Sciences, College of Natural Sciences, University of Ulsan) ;
  • Kim, Kwang Kon (Department of Biological Sciences, College of Natural Sciences, University of Ulsan) ;
  • Park, Jeong Woo (Department of Biological Sciences, College of Natural Sciences, University of Ulsan) ;
  • Lee, Byung Ju (Department of Biological Sciences, College of Natural Sciences, University of Ulsan)
  • Received : 2014.07.28
  • Accepted : 2014.11.12
  • Published : 2015.02.28
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Abstract

Continuous intra- and extracellular stresses induce disorder of $Ca^{2+}$ homeostasis and accumulation of unfolded protein in the endoplasmic reticulum (ER), which results in ER stress. Severe long-term ER stress triggers apoptosis signaling pathways, resulting in cell death. Neural epidermal growth factor-like like protein 2 (NELL2) has been reported to be important in protection of cells from cell death-inducing environments. In this study, we investigated the cytoprotective effect of NELL2 in the context of ER stress induced by thapsigargin, a strong ER stress inducer, in Cos7 cells. Overexpression of NELL2 prevented ER stress-mediated apoptosis by decreasing expression of ER stress-induced C/EBP homologous protein (CHOP) and increasing ER chaperones. In this context, expression of anti-apoptotic Bcl-xL was increased by NELL2, whereas NELL2 decreased expression of pro-apoptotic proteins, such as cleaved caspases 3 and 7. This anti-apoptotic effect of NELL2 is likely mediated by extracellular signal-regulated kinase (ERK) signaling, because its inhibitor, U0126, inhibited effects of NELL2 on the expression of anti- and pro-apoptotic proteins and on the protection from ER stress-induced cell death.

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References

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