PMID- 30146262 OWN - NLM STAT- MEDLINE DCOM- 20190108 LR - 20211204 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 503 IP - 4 DP - 2018 Sep 18 TI - Selenoprotein S protects against adipocyte death through mediation of the IRE1alpha-sXBP1 pathway. PG - 2866-2871 LID - S0006-291X(18)31739-X [pii] LID - 10.1016/j.bbrc.2018.08.057 [doi] AB - As the most conserved branch of the unfolded protein response (UPR), the inositol-requiring enzyme 1a (IRE1a)/X-box binding protein 1 (XBP1) pathway plays crucial roles in cell survival and cell death by upregulating UPR-associated genes involved in protein entry into the endoplasmic reticulum (ER) and ER-associated degradation (ERAD). Selenoprotein S (SelS) is localized to the ER membrane and involved in ERAD. Although SelS plays an important role in restoring ER stress, the SelS-dependent protective mechanisms against cell death remain unclear. Here, using an inducible SelS knockdown (KD) 3T3-L1 cell model, we showed that SelS KD resulted adipocyte death, which was associated with imbalance of the Bcl-2 family members. Furthermore, SelS KD decreased spliced XBP1 (sXBP1), increased IRE1alpha and p-JNK, suggesting a role of SelS in the modulation of the IRE1alpha-sXBP1 pathway. Moreover, adipocyte death induced by SelS suppression can be inhibited by overexpression of sXBP1. Thus, it is proposed that SelS promotes cell survival through the IRE1alpha-XBP1 signaling pathway. CI - Copyright (c) 2018. Published by Elsevier Inc. FAU - Men, Lili AU - Men L AD - Department of Endocrinology, The First Affiliated Hospital of Dalian Medical University, Dalian, China. FAU - Yu, Shanshan AU - Yu S AD - Department of Endocrinology, The First Affiliated Hospital of Dalian Medical University, Dalian, China. FAU - Yao, Junjie AU - Yao J AD - Department of Endocrinology, The First Affiliated Hospital of Dalian Medical University, Dalian, China. FAU - Li, Yu AU - Li Y AD - Department of Endocrinology, The First Affiliated Hospital of Dalian Medical University, Dalian, China. FAU - Ren, Decheng AU - Ren D AD - Department of Medicine, The University of Chicago, Chicago, IL, USA. Electronic address: decheng@uchicago.edu. FAU - Du, Jianling AU - Du J AD - Department of Endocrinology, The First Affiliated Hospital of Dalian Medical University, Dalian, China. Electronic address: dujianling63@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180824 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (RNA, Small Interfering) RN - 0 (Selenoproteins) RN - 0 (X-Box Binding Protein 1) RN - 0 (Xbp1 protein, mouse) RN - EC 2.7.11.1 (Ern1 protein, mouse) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.12.2 (MAP Kinase Kinase 4) RN - EC 3.1.- (Endoribonucleases) SB - IM MH - 3T3-L1 Cells MH - Adipocytes/cytology/*metabolism MH - Animals MH - Cell Death/*genetics MH - Cell Differentiation MH - Endoplasmic Reticulum/metabolism MH - Endoplasmic Reticulum Stress/genetics MH - *Endoplasmic Reticulum-Associated Degradation MH - Endoribonucleases/*genetics/metabolism MH - Gene Expression Regulation MH - MAP Kinase Kinase 4/genetics/metabolism MH - Mice MH - Protein Serine-Threonine Kinases/*genetics/metabolism MH - Protein Transport MH - RNA, Small Interfering/genetics/metabolism MH - Selenoproteins/antagonists & inhibitors/*genetics/metabolism MH - Signal Transduction MH - X-Box Binding Protein 1/*genetics/metabolism OTO - NOTNLM OT - Cell death OT - IRE1alpha OT - SelS OT - Spliced XBP1 EDAT- 2018/08/28 06:00 MHDA- 2019/01/09 06:00 CRDT- 2018/08/28 06:00 PHST- 2018/08/05 00:00 [received] PHST- 2018/08/06 00:00 [accepted] PHST- 2018/08/28 06:00 [pubmed] PHST- 2019/01/09 06:00 [medline] PHST- 2018/08/28 06:00 [entrez] AID - S0006-291X(18)31739-X [pii] AID - 10.1016/j.bbrc.2018.08.057 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2018 Sep 18;503(4):2866-2871. doi: 10.1016/j.bbrc.2018.08.057. Epub 2018 Aug 24.