title: NELL2 function in the protection of cells against endoplasmic reticulum stress.
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.
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan 680-749, Korea.
authors.forename: Dong Yeol
authors.initials: DY
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan 680-749, Korea.
authors.forename: Han Rae
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan 680-749, Korea.
authors.forename: Kwang Kon
authors.initials: KK
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan 680-749, Korea.
authors.forename: Jeong Woo
authors.initials: JW
authors.lastname: Park
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan 680-749, Korea.
authors.forename: Byung Ju
authors.initials: BJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis; D019556:COS Cells; D002522:Chlorocebus aethiops; D004721:Endoplasmic Reticulum / Q000502:physiology*; D059865:Endoplasmic Reticulum Stress; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology; D051742:Transcription Factor CHOP / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D051742:Transcription Factor CHOP; D019284:Thapsigargin
keywords: C/EBP homologous protein; caspase cascade; cell death; endoplasmic reticulum stress; extracellular signal-regulated kinase