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, D.Y., University of Ulsan, Ulsan, Republic of Korea, Kim, H.R., University of Ulsan, Ulsan, Republic of Korea, Kim, K.K., University of Ulsan, Ulsan, Republic of Korea, Park, J.W., University of Ulsan, Ulsan, Republic of Korea, Lee, B.J., University of Ulsan, Ulsan, Republic of Korea
• Format: Journal Article
• Language: English
• Published: United States Korean Society for Molecular and Cellular Biology 01.02.2015; 한국분자세포생물학회
• Subjects: Animals; Apoptosis; caspase cascade,C/EBP homologous protein,endoplasmic reticulum stress,extracellular signal-regulated kinase; CELL DEATH; Chlorocebus aethiops; COS Cells; Endoplasmic Reticulum - physiology; Endoplasmic Reticulum Stress; Enzyme Inhibitors - pharmacology; Gene Expression Regulation; MORT CELLULAIRE; MUERTE CELULAR; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Thapsigargin - pharmacology; Transcription Factor CHOP - metabolism; 생물학; caspase cascade; extracellular signal-regulated kinase; cell death; C/EBP homologous protein; endoplasmic reticulum stress
• ISSN: 1016-8478; 0219-1032; 0219-1032
• DOI: 10.14348/molcells.2015.2216

Continuous intra- and extracellular stresses induce disorder of Ca2+ 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 antiapoptotic 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.