1. Selenoprotein S protects against adipocyte death through mediation of the IRE1α-sXBP1 pathway.
- Author
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Men L, Yu S, Yao J, Li Y, Ren D, and Du J
- Subjects
- 3T3-L1 Cells, Adipocytes cytology, Animals, Cell Differentiation, Endoplasmic Reticulum metabolism, Endoplasmic Reticulum Stress genetics, Endoribonucleases metabolism, Gene Expression Regulation, MAP Kinase Kinase 4 genetics, MAP Kinase Kinase 4 metabolism, Mice, Protein Serine-Threonine Kinases metabolism, Protein Transport, RNA, Small Interfering genetics, RNA, Small Interfering metabolism, Selenoproteins antagonists & inhibitors, Selenoproteins metabolism, Signal Transduction, X-Box Binding Protein 1 metabolism, Adipocytes metabolism, Cell Death genetics, Endoplasmic Reticulum-Associated Degradation, Endoribonucleases genetics, Protein Serine-Threonine Kinases genetics, Selenoproteins genetics, X-Box Binding Protein 1 genetics
- Abstract
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 IRE1α and p-JNK, suggesting a role of SelS in the modulation of the IRE1α-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 IRE1α-XBP1 signaling pathway., (Copyright © 2018. Published by Elsevier Inc.)
- Published
- 2018
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