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学科主题基础医学
La3+ binds to BiP/GRP78 and induces unfolded protein response in HepG2 cells
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
2008-11-25
DOI10.1016/j.cbi.2008.07.014
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
WOS记录号WOS:000261557600015
项目编号20671008 ; 20637010
资助机构NSFC
引用统计
被引频次:8[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/65090
专题北京大学基础医学院
北京大学医学部管理机构_医学部
北京大学药学院_化学生物学系
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
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GB/T 7714
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.
APA Shen, Chenxi,Li, Zaiquan,Yang, Xiaoda,&Wang, Kui.(2008).La3+ binds to BiP/GRP78 and induces unfolded protein response in HepG2 cells.CHEMICO-BIOLOGICAL INTERACTIONS,176(2-3),196-203.
MLA Shen, Chenxi,et al."La3+ binds to BiP/GRP78 and induces unfolded protein response in HepG2 cells".CHEMICO-BIOLOGICAL INTERACTIONS 176.2-3(2008):196-203.
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