NELL2 Function in the Protection of Cells against Endoplasmic Reticulum Stress

• Published in: Molecules and cells Vol. 38; no. 2; pp. 145 - 150
• Main Authors: Kim, Dong Yeol, Kim, Han Rae, Kim, Kwang Kon, Park, Jeong Woo, Lee, Byung Ju
• Format: Journal Article
• Language: Korean
• Published: 2015
• Subjects: extracellular signal-regulated kinase; cell death; caspase cascade; C/EBP homologous protein; endoplasmic reticulum stress
• ISSN: 1016-8478; 0219-1032

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.