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学科主题: 基础医学
题名:
La3+ binds to BiP/GRP78 and induces unfolded protein response in HepG2 cells
作者: Shen, Chenxi2,3; Li, Zaiquan1; Yang, Xiaoda2,3; Wang, Kui2,3
关键词: Lanthanum ; Endoplasmic reticulum ; Unfolded protein response ; BiP/GRP78
刊名: CHEMICO-BIOLOGICAL INTERACTIONS
发表日期: 2008-11-25
DOI: 10.1016/j.cbi.2008.07.014
卷: 176, 期:2-3, 页:196-203
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Toxicology
研究领域[WOS]: Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Toxicology
关键词[WOS]: ENDOPLASMIC-RETICULUM STRESS ; CHRONIC-RENAL-FAILURE ; ER STRESS ; MESSENGER-RNA ; TRANSCRIPTION FACTOR ; CHAPERONE PROTEIN ; NIH 3T3-CELLS ; IRE1P KINASE ; CA2+ STORE ; LANTHANUM
英文摘要:

The effects of La3+ on the unfolded protein response signaling pathways were investigated in human hepatoblastoma HepG2 cells. Our data showed that La3+ could induce unfolded protein response in HepG2 cells, including a significant increase of BiP/GRP78 level, which is an important ER residential chaperone and an ER stress hallmark, in a concentration and time-dependent manner, UPR transducer IRE1 phosphorylation and splicing activation IRE1 downstream substrate XBP1 mRNA. By using La3+-affinity chromatography, the possible cellular target of La3+ leading to UPR events was shown to be the ER residential chaperone BiP/GRP78. BiP/GRP78 was shown to be a La3+ binding protein and the interaction of La3+ with BiP/GRP78 resulted in dissociation of BiP-IRE1 complexes. La3+ induced dissociation of the BiP/GRP78-IRE1 complex was in a time and concentration manner. The apparent dissociation constant was estimated to be 4 nM. In addition, La3+ was observed to slightly stimulate the production of cellular ROS and cause alteration of intracellular Ca2+, indicating the possible involvement of ROS and Ca2+ alteration in La3+ induced UPR. The present work provides a new perspective for understanding the biological and toxicological effects of La3+. (C) 2008 Published by Elsevier Ireland Ltd.

语种: 英语
所属项目编号: 20671008 ; 20637010
项目资助者: NSFC
WOS记录号: WOS:000261557600015
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/65090
Appears in Collections:基础医学院_期刊论文

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作者单位: 1.Peking Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Beijing 100191, Peoples R China
2.Peking Univ, State Key Labs Nat & Biomimet Drugs, Beijing 100191, Peoples R China
3.Peking Univ, Sch Pharmaceut Sci, Dept Biol Chem, Beijing 100191, Peoples R China

Recommended Citation:
Shen, Chenxi,Li, Zaiquan,Yang, Xiaoda,et al. La3+ binds to BiP/GRP78 and induces unfolded protein response in HepG2 cells[J]. CHEMICO-BIOLOGICAL INTERACTIONS,2008,176(2-3):196-203.
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