IRE1α dissociates with BiP and inhibits ER stress-mediated apoptosis in cartilage development

被引:40
作者
Han, Xiaofeng [1 ]
Zhou, Jinghua [1 ]
Zhang, Peng [1 ]
Song, Fangzhou [2 ]
Jiang, Rong [3 ]
Li, Meiling [1 ]
Xia, Fei [1 ]
Guo, Feng-Jin [1 ]
机构
[1] Chongqing Med Univ, Dept Cell Biol & Genet, Core Facil Dev Biol, Chongqing 400016, Peoples R China
[2] Chongqing Med Univ, Dept Biochem & Mol Biol, Chongqing 400016, Peoples R China
[3] Chongqing Med Univ, Lab Stem Cells & Tissue Engn, Chongqing 400016, Peoples R China
基金
美国国家科学基金会;
关键词
Endoplasmic reticulum stress; Apoptosis; UPR; IRE1; alpha; BiP; Cartilage development; ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; XBP1; MESSENGER-RNA; TRANSCRIPTION FACTOR; P204; PROTEIN; ATF6; ACTIVATION; IRE1; GROWTH; EXPRESSION;
D O I
10.1016/j.cellsig.2013.06.011
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Bone morphogenetic protein 2 is known to activate unfolded protein response signaling molecules, including XBP1S, BiP and IRE1 alpha. Endoplasmic reticulum stress is induced in chondrogenesis and activates IREl alpha signal pathway, which is associated with ER stress-mediated apoptosis. However, the influence on IRE1 alpha and BiP in BMP2-induced chondrocyte differentiation has not yet been elucidated; the molecular mechanism remains unexplored. In this study, we demonstrate that IRE1 alpha interacts with BiP in unstressed cells and dissociates from BiP in the course of cartilage development. Induction of ER stress-responsive proteins (XBP1S, IRE1 alpha, BiP) was also observed in differentiating cells. IRE1 alpha inhibition ER stress-mediated apoptosis lies in the process of chondrocyte differentiation. Furthermore, knockdown of IRE1 alpha expression by way of the RNAi approach accelerates ER stress-mediated apoptosis in chondrocyte differentiation induced by BMP2, as revealed by enhanced expressions of cleaved caspase3, CHOP and p-JNK1; and this IRE1 alpha inhibition effect on ER stress-mediated apoptosis is required for BiP in chondrogenesis. Collectively, the ER stress sensors were activated during apoptosis in cartilage development, suggesting that selective activation of ER stress signaling was sufficient for induction of apoptosis. These findings reveal a novel critical role of IRE1 alpha in ER stress-mediated apoptosis and the molecular mechanisms involved. These results suggest that activation of p-JNK1, caspase3 and CHOP was detected in developing chondrocytes and that specific ER stress signaling leads to naturally occurring apoptosis during cartilage development. Crown Copyright (C) 2013 Published by Elsevier Inc. All rights reserved.
引用
收藏
页码:2136 / 2146
页数:11
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