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http://dx.doi.org/10.14348/molcells.2015.2216

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)
Publication Information
Molecules and Cells / v.38, no.2, 2015 , pp. 145-150 More about this Journal
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.
Keywords
caspase cascade; C/EBP homologous protein; cell death; endoplasmic reticulum stress; extracellular signal-regulated kinase;
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